Publications of Ahmad Hariri
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@article{fds372228,
Author = {Lay-Yee, R and Hariri, AR and Knodt, AR and Barrett-Young, A and Matthews, T and Milne, BJ},
Title = {Social isolation from childhood to mid-adulthood: is there
an association with older brain age?},
Journal = {Psychological medicine},
Volume = {53},
Number = {16},
Pages = {7874-7882},
Year = {2023},
Month = {December},
Abstract = {<h4>Background</h4>Older brain age - as estimated from
structural MRI data - is known to be associated with
detrimental mental and physical health outcomes in older
adults. Social isolation, which has similar detrimental
effects on health, may be associated with accelerated brain
aging though little is known about how different
trajectories of social isolation across the life course
moderate this association. We examined the associations
between social isolation trajectories from age 5 to age 38
and brain age assessed at age 45.<h4>Methods</h4>We
previously created a typology of social isolation based on
onset during the life course and persistence into adulthood,
using group-based trajectory analysis of longitudinal data
from a New Zealand birth cohort. The typology comprises four
groups: 'never-isolated', 'adult-only', 'child-only', and
persistent 'child-adult' isolation. A brain age gap estimate
(brainAGE) - the difference between predicted age from
structural MRI date and chronological age - was derived at
age 45. We undertook analyses of brainAGE with trajectory
group as the predictor, adjusting for sex, family
socio-economic status, and a range of familial and
child-behavioral factors.<h4>Results</h4>Older brain age in
mid-adulthood was associated with trajectories of social
isolation after adjustment for family and child confounders,
particularly for the 'adult-only' group compared to the
'never-isolated' group.<h4>Conclusions</h4>Although our
findings are associational, they indicate that preventing
social isolation, particularly in mid-adulthood, may help to
avert accelerated brain aging associated with negative
health outcomes later in life.},
Doi = {10.1017/s0033291723001964},
Key = {fds372228}
}
@article{fds373508,
Author = {Knodt, AR and Elliott, ML and Whitman, ET and Winn, A and Addae, A and Ireland, D and Poulton, R and Ramrakha, S and Caspi, A and Moffitt, TE and Hariri, AR},
Title = {Test-retest reliability and predictive utility of a
macroscale principal functional connectivity
gradient.},
Journal = {Human brain mapping},
Volume = {44},
Number = {18},
Pages = {6399-6417},
Year = {2023},
Month = {December},
Abstract = {Mapping individual differences in brain function has been
hampered by poor reliability as well as limited
interpretability. Leveraging patterns of brain-wide
functional connectivity (FC) offers some promise in this
endeavor. In particular, a macroscale principal FC gradient
that recapitulates a hierarchical organization spanning
molecular, cellular, and circuit level features along a
sensory-to-association cortical axis has emerged as both a
parsimonious and interpretable measure of individual
differences in behavior. However, the measurement
reliabilities of this FC gradient have not been fully
evaluated. Here, we assess the reliabilities of both global
and regional principal FC gradient measures using
test-retest data from the young adult Human Connectome
Project (HCP-YA) and the Dunedin Study. Analyses revealed
that the reliabilities of principal FC gradient measures
were (1) consistently higher than those for traditional
edge-wise FC measures, (2) higher for FC measures derived
from general FC (GFC) in comparison with resting-state FC,
and (3) higher for longer scan lengths. We additionally
examined the relative utility of these principal FC gradient
measures in predicting cognition and aging in both datasets
as well as the HCP-aging dataset. These analyses revealed
that regional FC gradient measures and global gradient range
were significantly associated with aging in all three
datasets, and moderately associated with cognition in the
HCP-YA and Dunedin Study datasets, reflecting contractions
and expansions of the cortical hierarchy, respectively.
Collectively, these results demonstrate that measures of the
principal FC gradient, especially derived using GFC,
effectively capture a reliable feature of the human brain
subject to interpretable and biologically meaningful
individual variation, offering some advantages over
traditional edge-wise FC measures in the search for
brain-behavior associations.},
Doi = {10.1002/hbm.26517},
Key = {fds373508}
}
@article{fds370718,
Author = {Strauman, TJ and Hariri, AR},
Title = {Revising a Self-Regulation Phenotype for Depression Through
Individual Differences in Macroscale Brain
Organization.},
Journal = {Current directions in psychological science},
Volume = {32},
Number = {4},
Pages = {267-275},
Year = {2023},
Month = {August},
Abstract = {<i>Self-regulation</i> denotes the processes by which people
initiate, maintain, and control their own thoughts,
behaviors, or emotions to produce a desired outcome or avoid
an undesired outcome. Self-regulation brings the influence
of distal factors such as biology, temperament, and
socialization history onto cognition, motivation, and
behavior. Dysfunction in self-regulation represents a
contributory causal factor for psychopathology. Accordingly,
we previously proposed a risk phenotype model for depression
drawing from regulatory focus theory and traditional
task-based fMRI studies. In this article, we revise and
expand our risk phenotype model using insights from new
methodologies allowing quantification of individual
differences in task-free macroscale brain organization. We
offer a set of hypotheses as examples of how examination of
intrinsic macroscale brain organization can extend and
enrich investigations of self-regulation and depression. In
doing so, we hope to promote a useful heuristic for model
development and for identifying transdiagnostic risk
phenotypes in psychopathology.},
Doi = {10.1177/09637214221149742},
Key = {fds370718}
}
@article{fds371656,
Author = {Whitman, ET and Knodt, AR and Elliott, ML and Abraham, WC and Cheyne, K and Hogan, S and Ireland, D and Keenan, R and Leung, JH and Melzer, TR and Poulton, R and Purdy, SC and Ramrakha, S and Thorne, PR and Caspi, A and Moffitt, TE and Hariri, AR},
Title = {Functional topography of the neocortex predicts covariation
in complex cognitive and basic motor abilities.},
Journal = {Cerebral cortex (New York, N.Y. : 1991)},
Volume = {33},
Number = {13},
Pages = {8218-8231},
Year = {2023},
Month = {June},
Abstract = {Although higher-order cognitive and lower-order sensorimotor
abilities are generally regarded as distinct and studied
separately, there is evidence that they not only covary but
also that this covariation increases across the lifespan.
This pattern has been leveraged in clinical settings where a
simple assessment of sensory or motor ability (e.g. hearing,
gait speed) can forecast age-related cognitive decline and
risk for dementia. However, the brain mechanisms underlying
cognitive, sensory, and motor covariation are largely
unknown. Here, we examined whether such covariation in
midlife reflects variability in common versus distinct
neocortical networks using individualized maps of functional
topography derived from BOLD fMRI data collected in 769
45-year-old members of a population-representative cohort.
Analyses revealed that variability in basic motor but not
hearing ability reflected individual differences in the
functional topography of neocortical networks typically
supporting cognitive ability. These patterns suggest that
covariation in motor and cognitive abilities in midlife
reflects convergence of function in higher-order neocortical
networks and that gait speed may not be simply a measure of
physical function but rather an integrative index of nervous
system health.},
Doi = {10.1093/cercor/bhad109},
Key = {fds371656}
}
@article{fds362550,
Author = {Cobb, AR and Rubin, M and Stote, DL and Baldwin, BC and Lee, H-J and Hariri, AR and Telch, MJ},
Title = {Hippocampal volume and volume asymmetry prospectively
predict PTSD symptom emergence among Iraq-deployed
soldiers.},
Journal = {Psychological medicine},
Volume = {53},
Number = {5},
Pages = {1906-1913},
Year = {2023},
Month = {April},
Abstract = {<h4>Background</h4>Evidence suggests a link between smaller
hippocampal volume (HV) and post-traumatic stress disorder
(PTSD). However, there has been little prospective research
testing this question directly and it remains unclear
whether smaller HV confers risk or is a consequence of
traumatization and PTSD.<h4>Methods</h4>U.S. soldiers
(<i>N</i> = 107) completed a battery of clinical
assessments, including structural magnetic resonance imaging
pre-deployment. Once deployed they completed monthly
assessments of traumatic-stressors and symptoms. We
hypothesized that smaller HV would potentiate the effects of
traumatic stressors on PTSD symptoms in theater. Analyses
evaluated whether total HV, lateral (right <i>v.</i> left)
HV, or HV asymmetry (right - left) moderated the effects of
stressor-exposure during deployment on PTSD
symptoms.<h4>Results</h4>Findings revealed no interaction
between total HV and average monthly traumatic-stressors on
PTSD symptoms <i>b</i> = -0.028, <i>p</i> = 0.681 [95%
confidence interval (CI) -0.167 to 0.100]. However, in the
context of greater exposure to average monthly traumatic
stressors, greater right HV was associated with fewer PTSD
symptoms <i>b</i> = -0.467, <i>p</i> = 0.023 (95% CI -0.786
to -0.013), whereas greater left HV was unexpectedly
associated with greater PTSD symptoms <i>b</i> = 0.435,
<i>p</i> = 0.024 (95% CI 0.028-0.715).<h4>Conclusions</h4>Our
findings highlight the importance of considering the complex
role of HV, in particular HV asymmetry, in predicting the
emergence of PTSD symptoms in response to war-zone
trauma.},
Doi = {10.1017/s0033291721003548},
Key = {fds362550}
}
@article{fds370934,
Author = {Barrett-Young, A and Abraham, WC and Cheung, CY and Gale, J and Hogan,
S and Ireland, D and Keenan, R and Knodt, AR and Melzer, TR and Moffitt,
TE and Ramrakha, S and Tham, YC and Wilson, GA and Wong, TY and Hariri, AR and Poulton, R},
Title = {Associations Between Thinner Retinal Neuronal Layers and
Suboptimal Brain Structural Integrity in a Middle-Aged
Cohort.},
Journal = {Eye and brain},
Volume = {15},
Pages = {25-35},
Year = {2023},
Month = {January},
Abstract = {<h4>Purpose</h4>The retina has potential as a biomarker of
brain health and Alzheimer's disease (AD) because it is the
only part of the central nervous system which can be easily
imaged and has advantages over brain imaging technologies.
Few studies have compared retinal and brain measurements in
a middle-aged sample. The objective of our study was to
investigate whether retinal neuronal measurements were
associated with structural brain measurements in a
middle-aged population-based cohort.<h4>Participants and
methods</h4>Participants were members of the Dunedin
Multidisciplinary Health and Development Study (n=1037; a
longitudinal cohort followed from birth and at ages 3, 5, 7,
9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age
45, when 94% of the living Study members participated).
Retinal nerve fibre layer (RNFL) and ganglion cell-inner
plexiform layer (GC-IPL) thickness were measured by optical
coherence tomography (OCT). Brain age gap estimate
(brainAGE), cortical surface area, cortical thickness,
subcortical grey matter volumes, white matter
hyperintensities, were measured by magnetic resonance
imaging (MRI).<h4>Results</h4>Participants with both MRI and
OCT data were included in the analysis (RNFL n=828, female
n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female
n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal
layers were associated with older brain age, smaller
cortical surface area, thinner average cortex, smaller
subcortical grey matter volumes, and increased volume of
white matter hyperintensities.<h4>Conclusion</h4>These
findings provide evidence that the retinal neuronal layers
reflect differences in midlife structural brain integrity
consistent with increased risk for later AD, supporting the
proposition that the retina may be an early biomarker of
brain health.},
Doi = {10.2147/eb.s402510},
Key = {fds370934}
}
@article{fds365599,
Author = {Knodt, AR and Meier, MH and Ambler, A and Gehred, MZ and Harrington, H and Ireland, D and Poulton, R and Ramrakha, S and Caspi, A and Moffitt, TE and Hariri, AR},
Title = {Diminished Structural Brain Integrity in Long-term Cannabis
Users Reflects a History of Polysubstance
Use.},
Journal = {Biological psychiatry},
Volume = {92},
Number = {11},
Pages = {861-870},
Year = {2022},
Month = {December},
Abstract = {<h4>Background</h4>Cannabis legalization and use are
outpacing our understanding of its long-term effects on
brain and behavior, which is fundamental for effective
policy and health practices. Existing studies are limited by
small samples, cross-sectional measures, failure to separate
long-term from recreational use, and inadequate control for
other substance use. Here, we address these limitations by
determining the structural brain integrity of long-term
cannabis users in the Dunedin Study, a longitudinal
investigation of a population-representative birth cohort
followed to midlife.<h4>Methods</h4>We leveraged prospective
measures of cannabis, alcohol, tobacco, and other illicit
drug use in addition to structural neuroimaging in 875 study
members at age 45 to test for differences in both global and
regional gray and white matter integrity between long-term
cannabis users and lifelong nonusers. We additionally tested
for dose-response associations between continuous measures
of cannabis use and brain structure, including careful
adjustments for use of other substances.<h4>Results</h4>Long-term
cannabis users had a thinner cortex, smaller subcortical
gray matter volumes, and higher machine learning-predicted
brain age than nonusers. However, these differences in
structural brain integrity were explained by the propensity
of long-term cannabis users to engage in polysubstance use,
especially with alcohol and tobacco.<h4>Conclusions</h4>These
findings suggest that diminished midlife structural brain
integrity in long-term cannabis users reflects a broader
pattern of polysubstance use, underlining the importance of
understanding comorbid substance use in efforts to curb the
negative effects of cannabis on brain and behavior as well
as establish more effective policy and health
practices.},
Doi = {10.1016/j.biopsych.2022.06.018},
Key = {fds365599}
}
@article{fds367351,
Author = {Meier, MH and Caspi, A and Ambler, A and Hariri, AR and Harrington, H and Hogan, S and Houts, R and Knodt, AR and Ramrakha, S and Richmond-Rakerd,
LS and Poulton, R and Moffitt, TE},
Title = {Preparedness for healthy ageing and polysubstance use in
long-term cannabis users: a population-representative
longitudinal study.},
Journal = {The lancet. Healthy longevity},
Volume = {3},
Number = {10},
Pages = {e703-e714},
Year = {2022},
Month = {October},
Abstract = {<h4>Background</h4>Cannabis is often characterised as a
young person's drug. However, people who began consuming
cannabis in the 1970s and 1980s are no longer young and some
have consumed it for many years. This study tested the
preregistered hypothesis that long-term cannabis users show
accelerated biological ageing in midlife and poorer health
preparedness, financial preparedness, and social
preparedness for old age.<h4>Methods</h4>In this
longitudinal study, participants comprised a
population-representative cohort of 1037 individuals born in
Dunedin, New Zealand, between April, 1972, and March, 1973,
and followed to age 45 years. Cannabis, tobacco, and alcohol
use and dependence were assessed at ages 18 years, 21 years,
26 years, 32 years, 38 years, and 45 years. Biological
ageing and health, financial, and social preparedness for
old age were assessed at age 45 years. Long-term cannabis
users were compared using independent samples t tests with
five groups: lifelong cannabis non-users, long-term tobacco
users, long-term alcohol users, midlife recreational
cannabis users, and cannabis quitters. In addition,
regression analyses tested dose-response associations for
continuously measured persistence of cannabis dependence
from age 18 years to 45 years, with associations adjusted
for sex, childhood socioeconomic status, childhood IQ, low
childhood self-control, family substance dependence history,
and persistence of alcohol, tobacco, and other illicit drug
dependence.<h4>Findings</h4>Of 997 cohort members still
alive at age 45 years, 938 (94%) were assessed at age 45
years. Long-term cannabis users showed statistically
significant accelerated biological ageing and were less
equipped to manage a range of later-life health, financial,
and social demands than non-users. Standardised mean
differences between long-term cannabis users and non-users
were large: 0·70 (95% CI 0·46 to 0·94; p<0·0001) for
biological ageing, -0·72 (-0·96 to -0·49, p<0·0001) for
health preparedness, -1·08 (-1·31 to -0·85; p<0·0001)
for financial preparedness, and -0·59 (-0·84 to -0·34,
p<0·0001) for social preparedness. Long-term cannabis users
did not fare better than long-term tobacco or alcohol users.
Tests of dose-response associations suggested that cannabis
associations could not be explained by the socioeconomic
origins, childhood IQ, childhood self-control, and family
substance-dependence history of long-term cannabis users.
Statistical adjustment for long-term tobacco, alcohol, and
other illicit drug dependence suggested that long-term
cannabis users' tendency toward polysubstance dependence
accounted for their accelerated biological ageing and poor
financial and health preparedness, although not for their
poor social preparedness (β -0·10, 95% CI -0·18 to
-0·02; p=0·017).<h4>Interpretation</h4>Long-term cannabis
users are underprepared for the demands of old age. Although
long-term cannabis use appears detrimental, the greatest
challenge to healthy ageing is not use of any specific
substance, but rather the long-term polysubstance use that
characterises many long-term cannabis users. Substance-use
interventions should include practical strategies for
improving health and building financial and social capital
for healthy longevity.<h4>Funding</h4>The National Institute
on Aging and the UK Medical Research Council. The Dunedin
Research Unit is supported by the New Zealand Health
Research Council and the New Zealand Ministry of Business,
Innovation and Employment.},
Doi = {10.1016/s2666-7568(22)00201-x},
Key = {fds367351}
}
@article{fds366147,
Author = {Kim, MJ and Knodt, AR and Hariri, AR},
Title = {Meta-analytic activation maps can help identify affective
processes captured by contrast-based task fMRI: the case of
threat-related facial expressions.},
Journal = {Social cognitive and affective neuroscience},
Volume = {17},
Number = {9},
Pages = {777-787},
Year = {2022},
Month = {September},
Abstract = {Meta-analysis of functional magnetic resonance imaging
(fMRI) data is an effective method for capturing the
distributed patterns of brain activity supporting discrete
cognitive and affective processes. One opportunity presented
by the resulting meta-analysis maps (MAMs) is as a reference
for better understanding the nature of individual contrast
maps (ICMs) derived from specific task fMRI data. Here, we
compared MAMs from 148 neuroimaging studies representing
emotion categories of fear, anger, disgust, happiness and
sadness with ICMs from fearful > neutral and
angry > neutral faces from an independent dataset of
task fMRI (n = 1263). Analyses revealed that both fear
and anger ICMs exhibited the greatest pattern similarity to
fear MAMs. As the number of voxels included for the
computation of pattern similarity became more selective, the
specificity of MAM-ICM correspondence decreased. Notably,
amygdala activity long considered critical for processing
threat-related facial expressions was neither sufficient nor
necessary for detecting MAM-ICM pattern similarity effects.
Our analyses suggest that both fearful and angry facial
expressions are best captured by distributed patterns of
brain activity, a putative neural correlate of threat. More
generally, our analyses demonstrate how MAMs can be
leveraged to better understand affective processes captured
by ICMs in task fMRI data.},
Doi = {10.1093/scan/nsac010},
Key = {fds366147}
}
@article{fds367352,
Author = {Sugden, K and Caspi, A and Elliott, ML and Bourassa, KJ and Chamarti, K and Corcoran, DL and Hariri, AR and Houts, RM and Kothari, M and Kritchevsky, S and Kuchel, GA and Mill, JS and Williams, BS and Belsky,
DW and Moffitt, TE and Alzheimer's Disease Neuroimaging
Initiative*},
Title = {Association of Pace of Aging Measured by Blood-Based DNA
Methylation With Age-Related Cognitive Impairment and
Dementia.},
Journal = {Neurology},
Volume = {99},
Number = {13},
Pages = {e1402-e1413},
Year = {2022},
Month = {September},
Abstract = {<h4>Background and objectives</h4>DNA methylation algorithms
are increasingly used to estimate biological aging; however,
how these proposed measures of whole-organism biological
aging relate to aging in the brain is not known. We used
data from the Alzheimer's Disease Neuroimaging Initiative
(ADNI) and the Framingham Heart Study (FHS) Offspring Cohort
to test the association between blood-based DNA methylation
measures of biological aging and cognitive impairment and
dementia in older adults.<h4>Methods</h4>We tested 3
"generations" of DNA methylation age algorithms (first
generation: Horvath and Hannum clocks; second generation:
PhenoAge and GrimAge; and third generation: DunedinPACE,
Dunedin Pace of Aging Calculated from the Epigenome) against
the following measures of cognitive impairment in ADNI:
clinical diagnosis of dementia and mild cognitive
impairment, scores on Alzheimer disease (AD) / Alzheimer
disease and related dementias (ADRD) screening tests
(Alzheimer's Disease Assessment Scale, Mini-Mental State
Examination, and Montreal Cognitive Assessment), and scores
on cognitive tests (Rey Auditory Verbal Learning Test,
Logical Memory test, and Trail Making Test). In an
independent replication in the FHS Offspring Cohort, we
further tested the longitudinal association between the DNA
methylation algorithms and the risk of developing
dementia.<h4>Results</h4>In ADNI (<i>N</i> = 649
individuals), the first-generation (Horvath and Hannum DNA
methylation age clocks) and the second-generation (PhenoAge
and GrimAge) DNA methylation measures of aging were not
consistently associated with measures of cognitive
impairment in older adults. By contrast, a third-generation
measure of biological aging, DunedinPACE, was associated
with clinical diagnosis of Alzheimer disease (beta [95% CI]
= 0.28 [0.08-0.47]), poorer scores on Alzheimer disease/ADRD
screening tests (beta [Robust SE] = -0.10 [0.04] to
0.08[0.04]), and cognitive tests (beta [Robust SE] = -0.12
[0.04] to 0.10 [0.03]). The association between faster pace
of aging, as measured by DunedinPACE, and risk of developing
dementia was confirmed in a longitudinal analysis of the FHS
Offspring Cohort (<i>N</i> = 2,264 individuals, hazard ratio
[95% CI] = 1.27 [1.07-1.49]).<h4>Discussion</h4>Third-generation
blood-based DNA methylation measures of aging could prove
valuable for measuring differences between individuals in
the rate at which they age and in their risk for cognitive
decline, and for evaluating interventions to slow
aging.},
Doi = {10.1212/wnl.0000000000200898},
Key = {fds367352}
}
@article{fds364214,
Author = {Farber, MJ and Gee, DG and Hariri, AR},
Title = {Normative range parenting and the developing brain: A
scoping review and recommendations for future
research.},
Journal = {The European journal of neuroscience},
Volume = {55},
Number = {9-10},
Pages = {2341-2358},
Year = {2022},
Month = {May},
Abstract = {Studies of early adversity such as trauma, abuse, and
neglect highlight the critical importance of quality
caregiving in brain development and mental health. However,
the impact of normative range variability in caregiving on
such biobehavioral processes remains poorly understood.
Thus, we lack an essential foundation for understanding
broader, population-representative developmental mechanisms
of risk and resilience. Here, we conduct a scoping review of
the extant literature centered on the question, "Is
variability in normative range parenting associated with
variability in brain structure and function?" After removing
duplicates and screening by title, abstract, and full-text,
23 records were included in a qualitative review. The most
striking outcome of this review was not only how few studies
have explored associations between brain development and
normative range parenting, but also how little
methodological consistency exists across published studies.
In light of these limitations, we propose recommendations
for future research on normative range parenting and brain
development. In doing so, we hope to facilitate
evidence-based research that will help inform policies and
practices that yield optimal developmental trajectories and
mental health as well as extend the literature on the
neurodevelopmental impact of early life stress.},
Doi = {10.1111/ejn.15003},
Key = {fds364214}
}
@article{fds364180,
Author = {Kim, MJ and Elliott, ML and Knodt, AR and Hariri,
AR},
Title = {A Connectome-wide Functional Signature of Trait
Anger.},
Journal = {Clinical psychological science : a journal of the
Association for Psychological Science},
Volume = {10},
Number = {3},
Pages = {584-592},
Year = {2022},
Month = {May},
Abstract = {Past research on the brain correlates of trait anger has
been limited by small sample sizes, a focus on relatively
few regions-of-interest, and poor test-retest reliability of
functional brain measures. To address these limitations, we
conducted a data-driven analysis of variability in
connectome-wide functional connectivity in a sample of 1,048
young adult volunteers. Multi-dimensional matrix regression
analysis showed that self-reported trait anger maps onto
variability in the whole-brain functional connectivity
patterns of three brain regions that serve action-related
functions: bilateral supplementary motor area (SMA) and the
right lateral frontal pole. We then demonstrate trait anger
modulates the functional connectivity of these regions with
canonical brain networks supporting somatomotor, affective,
self-referential, and visual information processes. Our
findings offer novel neuroimaging evidence for interpreting
trait anger as a greater propensity to provoked action,
supporting ongoing efforts to understand its utility as a
potential transdiagnostic marker for disordered states
characterized by aggressive behavior.},
Doi = {10.1177/21677026211030240},
Key = {fds364180}
}
@article{fds364143,
Author = {Meier, MH and Caspi, A and R Knodt and A and Hall, W and Ambler, A and Harrington, H and Hogan, S and M Houts and R and Poulton, R and Ramrakha,
S and Hariri, AR and Moffitt, TE},
Title = {Long-Term Cannabis Use and Cognitive Reserves and
Hippocampal Volume in Midlife.},
Journal = {The American journal of psychiatry},
Volume = {179},
Number = {5},
Pages = {362-374},
Year = {2022},
Month = {May},
Abstract = {<h4>Objective</h4>Cannabis use is increasing among midlife
and older adults. This study tested the hypotheses that
long-term cannabis use is associated with cognitive deficits
and smaller hippocampal volume in midlife, which is
important because midlife cognitive deficits and smaller
hippocampal volume are risk factors for dementia.<h4>Methods</h4>Participants
are members of a representative cohort of 1,037 individuals
born in Dunedin, New Zealand, in 1972-1973 and followed to
age 45, with 94% retention. Cannabis use and dependence were
assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed
at ages 7, 9, 11, and 45. Specific neuropsychological
functions and hippocampal volume were assessed at age
45.<h4>Results</h4>Long-term cannabis users showed IQ
decline from childhood to midlife (mean=-5.5 IQ points),
poorer learning and processing speed relative to their
childhood IQ, and informant-reported memory and attention
problems. These deficits were specific to long-term cannabis
users because they were either not present or were smaller
among long-term tobacco users, long-term alcohol users,
midlife recreational cannabis users, and cannabis quitters.
Cognitive deficits among long-term cannabis users could not
be explained by persistent tobacco, alcohol, or other
illicit drug use, childhood socioeconomic status, low
childhood self-control, or family history of substance
dependence. Long-term cannabis users showed smaller
hippocampal volume, but smaller hippocampal volume did not
statistically mediate cannabis-related cognitive
deficits.<h4>Conclusions</h4>Long-term cannabis users showed
cognitive deficits and smaller hippocampal volume in
midlife. Research is needed to ascertain whether long-term
cannabis users show elevated rates of dementia in later
life.},
Doi = {10.1176/appi.ajp.2021.21060664},
Key = {fds364143}
}
@article{fds364171,
Author = {Bourassa, KJ and Moffitt, TE and Ambler, A and Hariri, AR and Harrington, H and Houts, RM and Ireland, D and Knodt, A and Poulton, R and Ramrakha, S and Caspi, A},
Title = {Association of Treatable Health Conditions During
Adolescence With Accelerated Aging at Midlife.},
Journal = {JAMA pediatrics},
Volume = {176},
Number = {4},
Pages = {392-399},
Year = {2022},
Month = {April},
Abstract = {<h4>Importance</h4>Biological aging is a distinct construct
from health; however, people who age quickly are more likely
to experience poor health. Identifying pediatric health
conditions associated with accelerated aging could help
develop treatment approaches to slow midlife aging and
prevent poor health in later life.<h4>Objective</h4>To
examine the association between 4 treatable health
conditions in adolescence and accelerated aging at
midlife.<h4>Design, setting, and participants</h4>This
cohort study analyzed data from participants in the Dunedin
Study, a longitudinal investigation of health and behavior
among a birth cohort born between April 1, 1972, and March
31, 1973, in Dunedin, New Zealand, and followed up until age
45 years. Participants underwent an assessment at age 45
years and had data for at least 1 adolescent health
condition (asthma, smoking, obesity, and psychological
disorders) and outcome measure (pace of aging, gait speed,
brain age, and facial age). Data analysis was performed from
February 11 to September 27, 2021.<h4>Exposures</h4>Asthma,
cigarette smoking, obesity, and psychological disorders were
assessed at age 11, 13, and 15 years.<h4>Main outcomes and
measures</h4>The outcome was a midlife aging factor
composite score comprising 4 measures of biological aging:
pace of aging, gait speed, brain age (specifically, BrainAGE
score), and facial age.<h4>Results</h4>A total of 910
participants (459 men [50.4%]) met the inclusion criteria,
including an assessment at age 45 years. Participants who
had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had
obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a
psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56]
SD units) during adolescence were biologically older at
midlife compared with participants without these conditions.
Participants with asthma were not biologically older at
midlife (0.02 [95% CI, -0.14 to 0.19] SD units) compared
with those without asthma. These results remained unchanged
after adjusting for childhood risk factors such as poor
health, socioeconomic disadvantage, and adverse
experiences.<h4>Conclusions and relevance</h4>This study
found that adolescent smoking, obesity, and psychological
disorder diagnoses were associated with older biological age
at midlife. These health conditions could be treated during
adolescence to reduce the risk of accelerated biological
aging later in life.},
Doi = {10.1001/jamapediatrics.2021.6417},
Key = {fds364171}
}
@article{fds364966,
Author = {Kragel, PA and Hariri, AR and LaBar, KS},
Title = {The Temporal Dynamics of Spontaneous Emotional Brain States
and Their Implications for Mental Health.},
Journal = {Journal of cognitive neuroscience},
Volume = {34},
Number = {5},
Pages = {715-728},
Year = {2022},
Month = {March},
Abstract = {Temporal processes play an important role in elaborating and
regulating emotional responding during routine mind
wandering. However, it is unknown whether the human brain
reliably transitions among multiple emotional states at rest
and how psychopathology alters these affect dynamics. Here,
we combined pattern classification and stochastic process
modeling to investigate the chronometry of spontaneous brain
activity indicative of six emotions (anger, contentment,
fear, happiness, sadness, and surprise) and a neutral state.
We modeled the dynamic emergence of these brain states
during resting-state fMRI and validated the results across
two population cohorts-the Duke Neurogenetics Study and the
Nathan Kline Institute Rockland Sample. Our findings
indicate that intrinsic emotional brain dynamics are
effectively characterized as a discrete-time Markov process,
with affective states organized around a neutral hub. The
centrality of this network hub is disrupted in individuals
with psychopathology, whose brain state transitions exhibit
greater inertia and less frequent resetting from emotional
to neutral states. These results yield novel insights into
how the brain signals spontaneous emotions and how
alterations in their temporal dynamics contribute to
compromised mental health.},
Doi = {10.1162/jocn_a_01787},
Key = {fds364966}
}
@article{fds368528,
Author = {Reuben, A and Moffitt, TE and Abraham, WC and Ambler, A and Elliott, ML and Hariri, AR and Harrington, H and Hogan, S and Houts, RM and Ireland, D and Knodt, AR and Leung, J and Pearson, A and Poulton, R and Purdy, SC and Ramrakha, S and Rasmussen, LJH and Sugden, K and Thorne, PR and Williams, B and Wilson, G and Caspi, A},
Title = {Improving risk indexes for Alzheimer's disease and related
dementias for use in midlife.},
Journal = {Brain communications},
Volume = {4},
Number = {5},
Pages = {fcac223},
Year = {2022},
Month = {January},
Abstract = {Knowledge of a person's risk for Alzheimer's disease and
related dementias (ADRDs) is required to triage candidates
for preventive interventions, surveillance, and treatment
trials. ADRD risk indexes exist for this purpose, but each
includes only a subset of known risk factors. Information
missing from published indexes could improve risk
prediction. In the Dunedin Study of a population-representative
New Zealand-based birth cohort followed to midlife
(<i>N</i> = 938, 49.5% female), we compared associations
of four leading risk indexes with midlife antecedents of
ADRD against a novel benchmark index comprised of nearly all
known ADRD risk factors, the Dunedin ADRD Risk Benchmark
(DunedinARB). Existing indexes included the Cardiovascular
Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle
for BRAin health index (LIBRA), Australian National
University Alzheimer's Disease Risk Index (ANU-ADRI), and
risks selected by the Lancet Commission on Dementia. The
Dunedin benchmark was comprised of 48 separate indicators of
risk organized into 10 conceptually distinct risk domains.
Midlife antecedents of ADRD treated as outcome measures
included age-45 measures of brain structural integrity
[magnetic resonance imaging-assessed: (i)
machine-learning-algorithm-estimated brain age, (ii)
log-transformed volume of white matter hyperintensities, and
(iii) mean grey matter volume of the hippocampus] and
measures of brain functional integrity [(i) objective
cognitive function assessed via the Wechsler Adult
Intelligence Scale-IV, (ii) subjective problems in everyday
cognitive function, and (iii) objective cognitive decline
measured as residualized change in cognitive scores from
childhood to midlife on matched Weschler Intelligence
scales]. All indexes were quantitatively distributed and
proved informative about midlife antecedents of ADRD,
including algorithm-estimated brain age (<i>β</i>'s from
0.16 to 0.22), white matter hyperintensities volume
(<i>β</i>'s from 0.16 to 0.19), hippocampal volume
(<i>β</i>'s from -0.08 to -0.11), tested cognitive deficits
(<i>β</i>'s from -0.36 to -0.49), everyday cognitive
problems (<i>β</i>'s from 0.14 to 0.38), and longitudinal
cognitive decline (<i>β</i>'s from -0.18 to -0.26).
Existing indexes compared favourably to the comprehensive
benchmark in their association with the brain structural
integrity measures but were outperformed in their
association with the functional integrity measures,
particularly subjective cognitive problems and tested
cognitive decline. Results indicated that existing indexes
could be improved with targeted additions, particularly of
measures assessing socioeconomic status, physical and
sensory function, epigenetic aging, and subjective overall
health. Existing premorbid ADRD risk indexes perform well in
identifying linear gradients of risk among members of the
general population at midlife, even when they include only a
small subset of potential risk factors. They could be
improved, however, with targeted additions to more
holistically capture the different facets of risk for this
multiply determined, age-related disease.},
Doi = {10.1093/braincomms/fcac223},
Key = {fds368528}
}
@article{fds364215,
Author = {Miles, AE and Dos Santos and FC and Byrne, EM and Renteria, ME and McIntosh, AM and Adams, MJ and Pistis, G and Castelao, E and Preisig, M and Baune, BT and Schubert, KO and Lewis, CM and Jones, LA and Jones, I and Uher, R and Smoller, JW and Perlis, RH and Levinson, DF and Potash, JB and Weissman, MM and Shi, J and Lewis, G and Penninx, BWJH and Boomsma, DI and Hamilton, SP and Major Depressive Disorder Working Group of the
Psychiatric Genomics Consortium, and Sibille, E and Hariri, AR and Nikolova, YS},
Title = {Transcriptome-based polygenic score links depression-related
corticolimbic gene expression changes to sex-specific brain
morphology and depression risk.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {46},
Number = {13},
Pages = {2304-2311},
Year = {2021},
Month = {December},
Abstract = {Studies in post-mortem human brain tissue have associated
major depressive disorder (MDD) with cortical transcriptomic
changes, whose potential in vivo impact remains unexplored.
To address this translational gap, we recently developed a
transcriptome-based polygenic risk score (T-PRS) based on
common functional variants capturing 'depression-like'
shifts in cortical gene expression. Here, we used a
non-clinical sample of young adults (n = 482, Duke
Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years)
to map T-PRS onto brain morphology measures, including
Freesurfer-derived subcortical volume, cortical thickness,
surface area, and local gyrification index, as well as broad
MDD risk, indexed by self-reported family history of
depression. We conducted side-by-side comparisons with a PRS
independently derived from a Psychiatric Genomics Consortium
(PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with
diagnosis and symptom severity directly in PGC-MDD
participants (n = 29,340, 59% women; 12,923 MDD cases,
16,417 controls). T-PRS was associated with smaller amygdala
volume in women (t = -3.478, p = 0.001) and lower
prefrontal gyrification across sexes. In men, T-PRS was
associated with hypergyrification in temporal and occipital
regions. Prefrontal hypogyrification mediated a
male-specific indirect link between T-PRS and familial
depression (b = 0.005, p = 0.029). PGC-PRS was
similarly associated with lower amygdala volume and cortical
gyrification; however, both effects were male-specific and
hypogyrification emerged in distinct parietal and
temporo-occipital regions, unassociated with familial
depression. In PGC-MDD, T-PRS did not predict diagnosis
(OR = 1.007, 95% CI = [0.997-1.018]) but correlated
with symptom severity in men (rho = 0.175,
p = 7.957 × 10<sup>-4</sup>) in one cohort
(N = 762, 48% men). Depression-like shifts in cortical
gene expression have sex-specific effects on brain
morphology and may contribute to broad depression
vulnerability in men.},
Doi = {10.1038/s41386-021-01189-x},
Key = {fds364215}
}
@article{fds368901,
Author = {Carlisi, CO and Moffitt, TE and Knodt, AR and Harrington, H and Langevin, S and Ireland, D and Melzer, TR and Poulton, R and Ramrakha,
S and Caspi, A and Hariri, AR and Viding, E},
Title = {Association of subcortical gray-matter volumes with
life-course-persistent antisocial behavior in a
population-representative longitudinal birth
cohort.},
Journal = {Development and psychopathology},
Pages = {1-11},
Year = {2021},
Month = {October},
Abstract = {Neuropsychological evidence supports the developmental
taxonomy theory of antisocial behavior, suggesting that
abnormal brain development distinguishes
life-course-persistent from adolescence-limited antisocial
behavior. Recent neuroimaging work confirmed that
prospectively-measured life-course-persistent antisocial
behavior is associated with differences in cortical brain
structure. Whether this extends to subcortical brain
structures remains uninvestigated. This study compared
subcortical gray-matter volumes between 672 members of the
Dunedin Study previously defined as exhibiting
life-course-persistent, adolescence-limited or low-level
antisocial behavior based on repeated assessments at ages
7-26 years. Gray-matter volumes of 10 subcortical structures
were compared across groups. The life-course-persistent
group had lower volumes of amygdala, brain stem, cerebellum,
hippocampus, pallidum, thalamus, and ventral diencephalon
compared to the low-antisocial group. Differences between
life-course-persistent and adolescence-limited individuals
were comparable in effect size to differences between
life-course-persistent and low-antisocial individuals, but
were not statistically significant due to less statistical
power. Gray-matter volumes in adolescence-limited
individuals were near the norm in this population-representative
cohort and similar to volumes in low-antisocial individuals.
Although this study could not establish causal links between
brain volume and antisocial behavior, it constitutes new
biological evidence that all people with antisocial behavior
are not the same, supporting a need for greater
developmental and diagnostic precision in clinical,
forensic, and policy-based interventions.},
Doi = {10.1017/s0954579421000377},
Key = {fds368901}
}
@article{fds364144,
Author = {Lam, M and Chen, C-Y and Ge, T and Xia, Y and Hill, DW and Trampush, JW and Yu, J and Knowles, E and Davies, G and Stahl, EA and Huckins, L and Liewald, DC and Djurovic, S and Melle, I and Christoforou, A and Reinvang, I and DeRosse, P and Lundervold, AJ and Steen, VM and Espeseth, T and Räikkönen, K and Widen, E and Palotie, A and Eriksson,
JG and Giegling, I and Konte, B and Hartmann, AM and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier, W and Chiba-Falek, O and Koltai, DC and Need, AC and Cirulli, ET and Voineskos, AN and Stefanis, NC and Avramopoulos, D and Hatzimanolis,
A and Smyrnis, N and Bilder, RM and Freimer, NB and Cannon, TD and London,
E and Poldrack, RA and Sabb, FW and Congdon, E and Conley, ED and Scult,
MA and Dickinson, D and Straub, RE and Donohoe, G and Morris, D and Corvin,
A and Gill, M and Hariri, AR and Weinberger, DR and Pendleton, N and Bitsios, P and Rujescu, D and Lahti, J and Le Hellard and S and Keller, MC and Andreassen, OA and Deary, IJ and Glahn, DC and Huang, H and Liu, C and Malhotra, AK and Lencz, T},
Title = {Identifying nootropic drug targets via large-scale cognitive
GWAS and transcriptomics.},
Journal = {Neuropsychopharmacology},
Volume = {46},
Number = {10},
Pages = {1788-1801},
Year = {2021},
Month = {September},
Abstract = {Broad-based cognitive deficits are an enduring and disabling
symptom for many patients with severe mental illness, and
these impairments are inadequately addressed by current
medications. While novel drug targets for schizophrenia and
depression have emerged from recent large-scale genome-wide
association studies (GWAS) of these psychiatric disorders,
GWAS of general cognitive ability can suggest potential
targets for nootropic drug repurposing. Here, we (1)
meta-analyze results from two recent cognitive GWAS to
further enhance power for locus discovery; (2) employ
several complementary transcriptomic methods to identify
genes in these loci that are credibly associated with
cognition; and (3) further annotate the resulting genes
using multiple chemoinformatic databases to identify
"druggable" targets. Using our meta-analytic data set
(N = 373,617), we identified 241 independent
cognition-associated loci (29 novel), and 76 genes were
identified by 2 or more methods of gene identification.
Actin and chromatin binding gene sets were identified as
novel pathways that could be targeted via drug repurposing.
Leveraging our transcriptomic and chemoinformatic databases,
we identified 16 putative genes targeted by existing drugs
potentially available for cognitive repurposing.},
Doi = {10.1038/s41386-021-01023-4},
Key = {fds364144}
}
@article{fds364145,
Author = {Elliott, ML and Knodt, AR and Hariri, AR},
Title = {Striving toward translation: strategies for reliable fMRI
measurement.},
Journal = {Trends in cognitive sciences},
Volume = {25},
Number = {9},
Pages = {776-787},
Year = {2021},
Month = {September},
Abstract = {fMRI has considerable potential as a translational tool for
understanding risk, prioritizing interventions, and
improving the treatment of brain disorders. However, recent
studies have found that many of the most widely used fMRI
measures have low reliability, undermining this potential.
Here, we argue that many fMRI measures are unreliable
because they were designed to identify group effects, not to
precisely quantify individual differences. We then highlight
four emerging strategies [extended aggregation, reliability
modeling, multi-echo fMRI (ME-fMRI), and stimulus design]
that build on established psychometric properties to
generate more precise and reliable fMRI measures. By
adopting such strategies to improve reliability, we are
optimistic that fMRI can fulfill its potential as a clinical
tool.},
Doi = {10.1016/j.tics.2021.05.008},
Key = {fds364145}
}
@article{fds347350,
Author = {Romer, AL and Knodt, AR and Sison, ML and Ireland, D and Houts, R and Ramrakha, S and Poulton, R and Keenan, R and Melzer, TR and Moffitt, TE and Caspi, A and Hariri, AR},
Title = {Replicability of structural brain alterations associated
with general psychopathology: evidence from a
population-representative birth cohort.},
Journal = {Molecular psychiatry},
Volume = {26},
Number = {8},
Pages = {3839-3846},
Year = {2021},
Month = {August},
Abstract = {Transdiagnostic research has identified a general
psychopathology factor-often called the 'p' factor-that
accounts for shared variation across internalizing,
externalizing, and thought disorders in diverse samples. It
has been argued that the p factor may reflect dysfunctional
thinking present in serious mental illness. In support of
this, we previously used a theory-free, data-driven
multimodal neuroimaging approach to find that higher p
factor scores are associated with structural alterations
within a cerebello-thalamo-cortical circuit (CTCC) and
visual association cortex, both of which are important for
monitoring and coordinating information processing in the
service of executive control. Here we attempt to replicate
these associations by conducting region-of-interest analyses
using data from 875 members of the Dunedin Longitudinal
Study, a five-decade study of a population-representative
birth cohort, collected when they were 45 years old. We
further sought to replicate a more recent report that p
factor scores can be predicted by patterns of distributed
cerebellar morphology as estimated through independent
component analysis. We successfully replicated associations
between higher p factor scores and both reduced gray matter
volume of the visual association cortex and fractional
anisotropy of pontine white matter pathways within the CTCC.
In contrast, we failed to replicate prior associations
between cerebellar structure and p factor scores.
Collectively, our findings encourage further focus on the
CTCC and visual association cortex as core neural substrates
and potential biomarkers of general psychopathology.},
Doi = {10.1038/s41380-019-0621-z},
Key = {fds347350}
}
@article{fds347349,
Author = {Elliott, ML and Belsky, DW and Knodt, AR and Ireland, D and Melzer, TR and Poulton, R and Ramrakha, S and Caspi, A and Moffitt, TE and Hariri,
AR},
Title = {Brain-age in midlife is associated with accelerated
biological aging and cognitive decline in a longitudinal
birth cohort.},
Journal = {Molecular psychiatry},
Volume = {26},
Number = {8},
Pages = {3829-3838},
Year = {2021},
Month = {August},
Abstract = {An individual's brainAGE is the difference between
chronological age and age predicted from machine-learning
models of brain-imaging data. BrainAGE has been proposed as
a biomarker of age-related deterioration of the brain.
Having an older brainAGE has been linked to Alzheimer's,
dementia, and mortality. However, these findings are largely
based on cross-sectional associations which can confuse age
differences with cohort differences. To illuminate the
validity of brainAGE as a biomarker of accelerated brain
aging, a study is needed of a large cohort all born in the
same year who nevertheless vary on brainAGE. In the Dunedin
Study, a population-representative 1972-73 birth cohort, we
measured brainAGE at age 45 years, as well as the pace of
biological aging and cognitive decline in longitudinal data
from childhood to midlife (N = 869). In this cohort, all
chronological age 45 years, brainAGE was measured reliably
(ICC = 0.81) and ranged from 24 to 72 years. Those with
older midlife brainAGEs tended to have poorer cognitive
function in both adulthood and childhood, as well as
impaired brain health at age 3. Furthermore, those with
older brainAGEs had an accelerated pace of biological aging,
older facial appearance, and early signs of cognitive
decline from childhood to midlife. These findings help to
validate brainAGE as a potential surrogate biomarker for
midlife intervention studies that seek to measure
dementia-prevention efforts in midlife. However, the
findings also caution against the assumption that brainAGE
scores represent only age-related deterioration of the brain
as they may also index central nervous system variation
present since childhood.},
Doi = {10.1038/s41380-019-0626-7},
Key = {fds347349}
}
@article{fds356131,
Author = {Gehred, MZ and Knodt, AR and Ambler, A and Bourassa, KJ and Danese, A and Elliott, ML and Hogan, S and Ireland, D and Poulton, R and Ramrakha, S and Reuben, A and Sison, ML and Moffitt, TE and Hariri, AR and Caspi,
A},
Title = {Long-term Neural Embedding of Childhood Adversity in a
Population-Representative Birth Cohort Followed for 5
Decades.},
Journal = {Biological psychiatry},
Volume = {90},
Number = {3},
Pages = {182-193},
Year = {2021},
Month = {August},
Abstract = {<h4>Background</h4>Childhood adversity has been previously
associated with alterations in brain structure, but
heterogeneous designs, methods, and measures have
contributed to mixed results and have impeded progress in
mapping the biological embedding of childhood adversity. We
sought to identify long-term differences in structural brain
integrity associated with childhood adversity.<h4>Methods</h4>Multiple
regression was used to test associations between
prospectively ascertained adversity during childhood and
adversity retrospectively reported in adulthood with
structural magnetic resonance imaging measures of midlife
global and regional cortical thickness, cortical surface
area, and subcortical gray matter volume in 861 (425 female)
members of the Dunedin Study, a longitudinal investigation
of a population-representative birth cohort.<h4>Results</h4>Both
prospectively ascertained childhood adversity and
retrospectively reported adversity were associated with
alterations in midlife structural brain integrity, but
associations with prospectively ascertained childhood
adversity were consistently stronger and more widely
distributed than associations with retrospectively reported
childhood adversity. Sensitivity analyses revealed that
these associations were not driven by any particular
adversity or category of adversity (i.e., threat or
deprivation) or by childhood socioeconomic disadvantage.
Network enrichment analyses revealed that these associations
were not localized but were broadly distributed along a
hierarchical cortical gradient of information
processing.<h4>Conclusions</h4>Exposure to childhood
adversity broadly is associated with widespread differences
in midlife gray matter across cortical and subcortical
structures, suggesting that biological embedding of
childhood adversity in the brain is long lasting, but not
localized. Research using retrospectively reported adversity
likely underestimates the magnitude of these associations.
These findings may inform future research investigating
mechanisms through which adversity becomes embedded in the
brain and influences mental health and cognition.},
Doi = {10.1016/j.biopsych.2021.02.971},
Key = {fds356131}
}
@article{fds364967,
Author = {Romer, AL and Hariri, AR and Strauman, TJ},
Title = {Regulatory focus and the p factor: Evidence for
self-regulatory dysfunction as a transdiagnostic feature of
general psychopathology.},
Journal = {Journal of psychiatric research},
Volume = {137},
Pages = {178-185},
Year = {2021},
Month = {May},
Abstract = {A general psychopathology ('p') factor captures
transdiagnostic features of mental illness; however, the
meaning of the p factor remains unclear. Regulatory focus
theory postulates that individuals regulate goal pursuit
either by maximizing gains (promotion) or minimizing losses
(prevention). As maladaptive goal pursuit has been
associated with multiple categorical disorders, we examined
whether individual differences in promotion and prevention
goal pursuit are associated with p as well as internalizing-
and externalizing-specific factors using structural equation
modeling of data from 1330 volunteers aged 18-22.
Unsuccessful attainment of promotion and prevention goals
was related to increased levels of p. Over and above
relations with the p factor, unsuccessful attainment of
promotion goals was associated with higher
internalizing-specific psychopathology, whereas unsuccessful
attainment of prevention goals was related to higher
externalizing-specific psychopathology. These associations
also were separable from related personality traits. After
controlling for sex differences in the composition of the
psychopathology factors, there were no sex differences in
the relations between promotion and prevention goal pursuit
and p and specific internalizing and externalizing factors.
These findings suggest higher general psychopathology
reflects poorer overall self-regulation of goal pursuit and
that maladaptive promotion and prevention orientations also
are associated with internalizing- and externalizing-specific
psychopathology, respectively.},
Doi = {10.1016/j.jpsychires.2021.02.051},
Key = {fds364967}
}
@article{fds364968,
Author = {Elliott, ML and Knodt, AR and Caspi, A and Moffitt, TE and Hariri,
AR},
Title = {Need for Psychometric Theory in Neuroscience Research and
Training: Reply to Kragel et al. (2021).},
Journal = {Psychological science},
Volume = {32},
Number = {4},
Pages = {627-629},
Year = {2021},
Month = {April},
Doi = {10.1177/0956797621996665},
Key = {fds364968}
}
@article{fds364216,
Author = {Pfeiffer, JR and Bustamante, AC and Kim, GS and Armstrong, D and Knodt,
AR and Koenen, KC and Hariri, AR and Uddin, M},
Title = {Associations between childhood family emotional health,
fronto-limbic grey matter volume, and saliva 5mC in young
adulthood.},
Journal = {Clinical epigenetics},
Volume = {13},
Number = {1},
Pages = {68},
Year = {2021},
Month = {March},
Abstract = {<h4>Background</h4>Poor family emotional health (FEH) during
childhood is prevalent and impactful, and likely confers
similar neurodevelopmental risks as other adverse social
environments. Pointed FEH study efforts are underdeveloped,
and the mechanisms by which poor FEH are biologically
embedded are unclear. The current exploratory study examined
whether variability in 5-methyl-cytosine (5mC) and
fronto-limbic grey matter volume may represent pathways
through which FEH may become biologically
embedded.<h4>Results</h4>In 98 university students aged
18-22 years, retrospective self-reported childhood FEH was
associated with right hemisphere hippocampus (b = 10.4,
p = 0.005), left hemisphere amygdala (b = 5.3,
p = 0.009), and right hemisphere amygdala (b = 5.8,
p = 0.016) volumes. After pre-processing and filtering
to 5mC probes correlated between saliva and brain, analyses
showed that childhood FEH was associated with 49 5mC
principal components (module eigengenes; MEs)
(p<sub>range</sub> = 3 × 10<sup>-6</sup> to 0.047).
Saliva-derived 5mC MEs partially mediated the association
between FEH and right hippocampal volume (Burlywood ME
indirect effect b = - 111, p = 0.014), and fully
mediated the FEH and right amygdala volume relationship
(Pink4 ME indirect effect b = - 48, p = 0.026).
Modules were enriched with probes falling in genes with
immune, central nervous system (CNS), cellular
development/differentiation, and metabolic
functions.<h4>Conclusions</h4>Findings extend work
highlighting neurodevelopmental variability associated with
adverse social environment exposure during childhood by
specifically implicating poor FEH, while informing a
mechanism of biological embedding. FEH-associated epigenetic
signatures could function as proxies of altered
fronto-limbic grey matter volume associated with poor
childhood FEH and inform further investigation into
primarily affected tissues such as endocrine, immune, and
CNS cell types.},
Doi = {10.1186/s13148-021-01056-y},
Key = {fds364216}
}
@article{fds364162,
Author = {Elliott, ML and Caspi, A and Houts, RM and Ambler, A and Broadbent, JM and Hancox, RJ and Harrington, H and Hogan, S and Keenan, R and Knodt, A and Leung, JH and Melzer, TR and Purdy, SC and Ramrakha, S and Richmond-Rakerd, LS and Righarts, A and Sugden, K and Thomson, WM and Thorne, PR and Williams, BS and Wilson, G and Hariri, AR and Poulton, R and Moffitt, TE},
Title = {Disparities in the pace of biological aging among midlife
adults of the same chronological age have implications for
future frailty risk and policy.},
Journal = {Nature aging},
Volume = {1},
Number = {3},
Pages = {295-308},
Year = {2021},
Month = {March},
Abstract = {Some humans age faster than others. Variation in biological
aging can be measured in midlife, but the implications of
this variation are poorly understood. We tested associations
between midlife biological aging and indicators of future
frailty-risk in the Dunedin cohort of 1037 infants born the
same year and followed to age 45. Participants' Pace of
Aging was quantified by tracking declining function in 19
biomarkers indexing the cardiovascular, metabolic, renal,
immune, dental, and pulmonary systems across ages 26, 32,
38, and 45 years. At age 45 in 2019, participants with
faster Pace of Aging had more cognitive difficulties, signs
of advanced brain aging, diminished sensory-motor functions,
older appearance, and more pessimistic perceptions of aging.
People who are aging more rapidly than same-age peers in
midlife may prematurely need supports to sustain
independence that are usually reserved for older adults.
Chronological age does not adequately identify need for such
supports.},
Doi = {10.1038/s43587-021-00044-4},
Key = {fds364162}
}
@article{fds364217,
Author = {Mareckova, K and Hawco, C and Santos, FCD and Bakht, A and Calarco, N and Miles, AE and Voineskos, AN and Sibille, E and Hariri, AR and Nikolova,
YS},
Title = {Correction: Novel polygenic risk score as a translational
tool linking depression-related changes in the corticolimbic
transcriptome with neural face processing and anhedonic
symptoms.},
Journal = {Translational psychiatry},
Volume = {11},
Number = {1},
Pages = {152},
Year = {2021},
Month = {March},
Doi = {10.1038/s41398-021-01277-y},
Key = {fds364217}
}
@article{fds364969,
Author = {Romer, AL and Elliott, ML and Knodt, AR and Sison, ML and Ireland, D and Houts, R and Ramrakha, S and Poulton, R and Keenan, R and Melzer, TR and Moffitt, TE and Caspi, A and Hariri, AR},
Title = {Pervasively Thinner Neocortex as a Transdiagnostic Feature
of General Psychopathology.},
Journal = {The American journal of psychiatry},
Volume = {178},
Number = {2},
Pages = {174-182},
Year = {2021},
Month = {February},
Abstract = {<h4>Objective</h4>Neuroimaging research has revealed that
structural brain alterations are common across broad
diagnostic families of disorders rather than specific to a
single psychiatric disorder. Such overlap in the structural
brain correlates of mental disorders mirrors already
well-documented phenotypic comorbidity of psychiatric
symptoms and diagnoses, which can be indexed by a general
psychopathology or <i>p</i> factor. The authors hypothesized
that if general psychopathology drives the convergence of
structural alterations common across disorders, then 1)
there should be few associations unique to any one
diagnostic family of disorders, and 2) associations with the
<i>p</i> factor should overlap with those for the broader
diagnostic families.<h4>Methods</h4>Analyses were conducted
on structural MRI and psychopathology data collected from
861 members of the population-representative Dunedin
Multidisciplinary Health and Development Study at age
45.<h4>Results</h4>Study members with high scores across
three broad diagnostic families of disorders (externalizing,
internalizing, thought disorder) exhibited highly
overlapping patterns of reduced global and widely
distributed parcel-wise neocortical thickness. Study members
with high <i>p</i> factor scores exhibited patterns of
reduced global and parcel-wise neocortical thickness nearly
identical to those associated with the three broad
diagnostic families.<h4>Conclusions</h4>A pattern of
pervasively reduced neocortical thickness appears to be
common across all forms of mental disorders and may
represent a transdiagnostic feature of general
psychopathology. As has been documented with regard to
symptoms and diagnoses, the underlying brain structural
correlates of mental disorders may not exhibit specificity,
and the continued pursuit of such specific correlates may
limit progress toward more effective strategies for
etiological understanding, prevention, and
intervention.},
Doi = {10.1176/appi.ajp.2020.19090934},
Key = {fds364969}
}
@article{fds364181,
Author = {Richmond-Rakerd, LS and Caspi, A and Ambler, A and d'Arbeloff, T and de
Bruine, M and Elliott, M and Harrington, H and Hogan, S and Houts, RM and Ireland, D and Keenan, R and Knodt, AR and Melzer, TR and Park, S and Poulton, R and Ramrakha, S and Rasmussen, LJH and Sack, E and Schmidt,
AT and Sison, ML and Wertz, J and Hariri, AR and Moffitt,
TE},
Title = {Childhood self-control forecasts the pace of midlife aging
and preparedness for old age.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {118},
Number = {3},
Pages = {e2010211118},
Year = {2021},
Month = {January},
Abstract = {The ability to control one's own emotions, thoughts, and
behaviors in early life predicts a range of positive
outcomes in later life, including longevity. Does it also
predict how well people age? We studied the association
between self-control and midlife aging in a
population-representative cohort of children followed from
birth to age 45 y, the Dunedin Study. We measured children's
self-control across their first decade of life using a
multi-occasion/multi-informant strategy. We measured their
pace of aging and aging preparedness in midlife using
measures derived from biological and physiological
assessments, structural brain-imaging scans, observer
ratings, self-reports, informant reports, and administrative
records. As adults, children with better self-control aged
more slowly in their bodies and showed fewer signs of aging
in their brains. By midlife, these children were also better
equipped to manage a range of later-life health, financial,
and social demands. Associations with children's
self-control could be separated from their social class
origins and intelligence, indicating that self-control might
be an active ingredient in healthy aging. Children also
shifted naturally in their level of self-control across
adult life, suggesting the possibility that self-control may
be a malleable target for intervention. Furthermore,
individuals' self-control in adulthood was associated with
their aging outcomes after accounting for their self-control
in childhood, indicating that midlife might offer another
window of opportunity to promote healthy
aging.},
Doi = {10.1073/pnas.2010211118},
Key = {fds364181}
}
@article{fds364146,
Author = {d'Arbeloff, T and Elliott, ML and Knodt, AR and Sison, M and Melzer, TR and Ireland, D and Ramrakha, S and Poulton, R and Caspi, A and Moffitt, TE and Hariri, AR},
Title = {Midlife Cardiovascular Fitness Is Reflected in the Brain's
White Matter.},
Journal = {Frontiers in aging neuroscience},
Volume = {13},
Pages = {652575},
Year = {2021},
Month = {January},
Abstract = {Disappointing results from clinical trials designed to delay
structural brain decline and the accompanying increase in
risk for dementia in older adults have precipitated a shift
in testing promising interventions from late in life toward
midlife before irreversible damage has accumulated. This
shift, however, requires targeting midlife biomarkers that
are associated with clinical changes manifesting only in
late life. Here we explored possible links between one
putative biomarker, distributed integrity of brain white
matter, and two intervention targets, cardiovascular fitness
and healthy lifestyle behaviors, in midlife. At age 45,
fractional anisotropy (FA) derived from diffusion weighted
MRI was used to estimate the microstructural integrity of
distributed white matter tracts in a population-representative
birth cohort. Age-45 cardiovascular fitness
(VO<sub>2</sub>Max; <i>N</i> = 801) was estimated from heart
rates obtained during submaximal exercise tests; age-45
healthy lifestyle behaviors were estimated using the Nyberg
Health Index (<i>N</i> = 854). Ten-fold cross-validated
elastic net predictive modeling revealed that estimated
VO<sub>2</sub>Max was modestly associated with distributed
FA. In contrast, there was no significant association
between Nyberg Health Index scores and FA. Our findings
suggest that cardiovascular fitness levels, but not healthy
lifestyle behaviors, are associated with the distributed
integrity of white matter in the brain in midlife. These
patterns could help inform future clinical intervention
research targeting ADRDs.},
Doi = {10.3389/fnagi.2021.652575},
Key = {fds364146}
}
@article{fds364970,
Author = {Rasmussen, LJH and Caspi, A and Ambler, A and Danese, A and Elliott, M and Eugen-Olsen, J and Hariri, AR and Harrington, H and Houts, R and Poulton, R and Ramrakha, S and Sugden, K and Williams, B and Moffitt,
TE},
Title = {Association Between Elevated suPAR, a New Biomarker of
Inflammation, and Accelerated Aging.},
Journal = {The journals of gerontology. Series A, Biological sciences
and medical sciences},
Volume = {76},
Number = {2},
Pages = {318-327},
Year = {2021},
Month = {January},
Abstract = {<h4>Background</h4>To understand and measure the association
between chronic inflammation, aging, and age-related
diseases, broadly applicable standard biomarkers of systemic
chronic inflammation are needed. We tested whether elevated
blood levels of the emerging chronic inflammation marker
soluble urokinase plasminogen activator receptor (suPAR)
were associated with accelerated aging, lower functional
capacity, and cognitive decline.<h4>Methods</h4>We used data
from the Dunedin Study, a population-representative
1972-1973 New Zealand birth cohort (n = 1037) that has
observed participants to age 45 years. Plasma suPAR levels
were analyzed at ages 38 and 45 years. We performed
regression analyses adjusted for sex, smoking, C-reactive
protein, and current health conditions.<h4>Results</h4>Of
997 still-living participants, 875 (88%) had plasma suPAR
measured at age 45. Elevated suPAR was associated with
accelerated pace of biological aging across multiple organ
systems, older facial appearance, and with structural signs
of older brain age. Moreover, participants with higher suPAR
levels had greater decline in physical function and
cognitive function from childhood to adulthood compared to
those with lower suPAR levels. Finally, improvements in
health habits between ages 38 and 45 (smoking cessation or
increased physical activity) were associated with less steep
increases in suPAR levels over those years.<h4>Conclusions</h4>Our
findings provide initial support for the utility of suPAR in
studying the role of chronic inflammation in accelerated
aging and functional decline.},
Doi = {10.1093/gerona/glaa178},
Key = {fds364970}
}
@article{fds354222,
Author = {Gianaros, PJ and Kraynak, TE and Kuan, DC-H and Gross, JJ and McRae, K and Hariri, AR and Manuck, SB and Rasero, J and Verstynen,
TD},
Title = {Affective brain patterns as multivariate neural correlates
of cardiovascular disease risk.},
Journal = {Social cognitive and affective neuroscience},
Volume = {15},
Number = {10},
Pages = {1034-1045},
Year = {2020},
Month = {November},
Abstract = {This study tested whether brain activity patterns evoked by
affective stimuli relate to individual differences in an
indicator of pre-clinical atherosclerosis: carotid artery
intima-media thickness (CA-IMT). Adults (aged 30-54 years)
completed functional magnetic resonance imaging (fMRI) tasks
that involved viewing three sets of affective stimuli. Two
sets included facial expressions of emotion, and one set
included neutral and unpleasant images from the
International Affective Picture System (IAPS).
Cross-validated, multivariate and machine learning models
showed that individual differences in CA-IMT were partially
predicted by brain activity patterns evoked by unpleasant
IAPS images, even after accounting for age, sex and known
cardiovascular disease risk factors. CA-IMT was also
predicted by brain activity patterns evoked by angry and
fearful faces from one of the two stimulus sets of facial
expressions, but this predictive association did not persist
after accounting for known cardiovascular risk factors. The
reliability (internal consistency) of brain activity
patterns evoked by affective stimuli may have constrained
their prediction of CA-IMT. Distributed brain activity
patterns could comprise affective neural correlates of
pre-clinical atherosclerosis; however, the interpretation of
such correlates may depend on their psychometric properties,
as well as the influence of other cardiovascular risk
factors and specific affective cues.},
Doi = {10.1093/scan/nsaa050},
Key = {fds354222}
}
@article{fds364139,
Author = {Reuben, A and Elliott, ML and Abraham, WC and Broadbent, J and Houts,
RM and Ireland, D and Knodt, AR and Poulton, R and Ramrakha, S and Hariri,
AR and Caspi, A and Moffitt, TE},
Title = {Association of Childhood Lead Exposure With MRI Measurements
of Structural Brain Integrity in Midlife.},
Journal = {JAMA},
Volume = {324},
Number = {19},
Pages = {1970-1979},
Year = {2020},
Month = {November},
Abstract = {<h4>Importance</h4>Childhood lead exposure has been linked
to disrupted brain development, but long-term consequences
for structural brain integrity are unknown.<h4>Objective</h4>To
test the hypothesis that childhood lead exposure is
associated with magnetic resonance imaging (MRI)
measurements of lower structural integrity of the brain in
midlife.<h4>Design, setting, and participants</h4>The
Dunedin Study followed a population-representative 1972-1973
birth cohort in New Zealand (N = 564 analytic sample) to
age 45 years (until April 2019).<h4>Exposures</h4>Childhood
blood lead levels measured at age 11 years.<h4>Main outcomes
and measures</h4>Structural brain integrity at age 45 years
assessed via MRI (primary outcomes): gray matter (cortical
thickness, surface area, hippocampal volume), white matter
(white matter hyperintensities, fractional anisotropy
[theoretical range, 0 {diffusion is perfectly isotropic} to
100 {diffusion is perfectly anisotropic}]), and the Brain
Age Gap Estimation (BrainAGE), a composite index of the gap
between chronological age and a machine learning
algorithm-estimated brain age (0 indicates a brain age
equivalent to chronological age; positive and negative
values represent an older and younger brain age,
respectively). Cognitive function at age 45 years was
assessed objectively via the Wechsler Adult Intelligence
Scale IV (IQ range, 40-160, standardized to a mean of 100
[SD, 15]) and subjectively via informant and self-reports
(z-score units; scale mean, 0 [SD, 1]).<h4>Results</h4>Of
1037 original participants, 997 were alive at age 45 years,
of whom 564 (57%) had received lead testing at age 11 years
(302 [54%] male) (median follow-up, 34 [interquartile range,
33.7-34.7] years). Mean blood lead level at age 11 years was
10.99 (SD, 4.63) μg/dL. After adjusting for covariates,
each 5-μg/dL higher childhood blood lead level was
significantly associated with 1.19-cm2 smaller cortical
surface area (95% CI, -2.35 to -0.02 cm2; P = .05),
0.10-cm3 smaller hippocampal volume (95% CI, -0.17 to -0.03
cm3; P = .006), lower global fractional anisotropy
(b = -0.12; 95% CI, -0.24 to -0.01; P = .04), and a
BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years;
P = .05) at age 45 years. There were no statistically
significant associations between blood lead level and
log-transformed white matter hyperintensity volume
(b = 0.05 log mm3; 95% CI, -0.02 to 0.13 log mm3;
P = .17) or mean cortical thickness (b = -0.004 mm;
95% CI, -0.012 to 0.004 mm; P = .39). Each 5-μg/dL
higher childhood blood lead level was significantly
associated with a 2.07-point lower IQ score at age 45 years
(95% CI, -3.39 to -0.74; P = .002) and a 0.12-point
higher score on informant-rated cognitive problems (95% CI,
0.01-0.23; P = .03). There was no statistically
significant association between childhood blood lead levels
and self-reported cognitive problems (b = -0.02 points;
95% CI, -0.10 to 0.07; P = .68).<h4>Conclusions and
relevance</h4>In this longitudinal cohort study with a
median 34-year follow-up, higher childhood blood lead level
was associated with differences in some MRI measures of
brain structure that suggested lower structural brain
integrity in midlife. Because of the large number of
statistical comparisons, some findings may represent type I
error.},
Doi = {10.1001/jama.2020.19998},
Key = {fds364139}
}
@article{fds364218,
Author = {Mareckova, K and Hawco, C and Dos Santos and FC and Bakht, A and Calarco,
N and Miles, AE and Voineskos, AN and Sibille, E and Hariri, AR and Nikolova, YS},
Title = {Novel polygenic risk score as a translational tool linking
depression-related changes in the corticolimbic
transcriptome with neural face processing and anhedonic
symptoms.},
Journal = {Translational psychiatry},
Volume = {10},
Number = {1},
Pages = {410},
Year = {2020},
Month = {November},
Abstract = {Convergent data from imaging and postmortem brain
transcriptome studies implicate corticolimbic circuit (CLC)
dysregulation in the pathophysiology of depression. To more
directly bridge these lines of work, we generated a novel
transcriptome-based polygenic risk score (T-PRS), capturing
subtle shifts toward depression-like gene expression
patterns in key CLC regions, and mapped this T-PRS onto
brain function and related depressive symptoms in a
nonclinical sample of 478 young adults (225 men; age
19.79 +/- 1.24) from the Duke Neurogenetics Study.
First, T-PRS was generated based on common functional SNPs
shifting CLC gene expression toward a depression-like state.
Next, we used multivariate partial least squares regression
to map T-PRS onto whole-brain activity patterns during
perceptual processing of social stimuli (i.e., human faces).
For validation, we conducted a comparative analysis with a
PRS summarizing depression risk variants identified by the
Psychiatric Genomics Consortium (PGC-PRS). Sex was modeled
as moderating factor. We showed that T-PRS was associated
with widespread reductions in neural response to neutral
faces in women and to emotional faces and shapes in men
(multivariate p < 0.01). This female-specific reductions
in neural response to neutral faces was also associated with
PGC-PRS (multivariate p < 0.03). Reduced reactivity to
neutral faces was further associated with increased
self-reported anhedonia. We conclude that women with
functional alleles mimicking the postmortem transcriptomic
CLC signature of depression have blunted neural activity to
social stimuli, which may be expressed as higher
anhedonia.},
Doi = {10.1038/s41398-020-01093-w},
Key = {fds364218}
}
@article{fds364140,
Author = {d'Arbeloff, T and Cooke, M and Knodt, AR and Sison, M and Melzer, TR and Ireland, D and Poulton, R and Ramrakha, S and Moffitt, TE and Caspi, A and Hariri, AR},
Title = {Is cardiovascular fitness associated with structural brain
integrity in midlife? Evidence from a population-representative
birth cohort study.},
Journal = {Aging},
Volume = {12},
Number = {20},
Pages = {20888-20914},
Year = {2020},
Month = {October},
Abstract = {Improving cardiovascular fitness may buffer against
age-related cognitive decline and mitigate dementia risk by
staving off brain atrophy. However, it is unclear if such
effects reflect factors operating in childhood
(neuroselection) or adulthood (neuroprotection). Using data
from 807 members of the Dunedin Study, a
population-representative birth cohort, we investigated
associations between cardiovascular fitness and structural
brain integrity at age 45, and the extent to which
associations reflected possible neuroselection or
neuroprotection by controlling for childhood IQ. Higher
fitness, as indexed by VO<sub>2</sub>Max, was not associated
with average cortical thickness, total surface area, or
subcortical gray matter volume including the hippocampus.
However, higher fitness was associated with thicker cortex
in prefrontal and temporal regions as well as greater
cerebellar gray matter volume. Higher fitness was also
associated with decreased hippocampal fissure volume. These
associations were unaffected by the inclusion of childhood
IQ in analyses. In contrast, a higher rate of decline in
cardiovascular fitness from 26 to 45 years was not robustly
associated with structural brain integrity. Our findings are
consistent with a neuroprotective account of adult
cardiovascular fitness but suggest that effects are not
uniformly observed across the brain and reflect
contemporaneous fitness more so than decline over
time.},
Doi = {10.18632/aging.104112},
Key = {fds364140}
}
@article{fds364219,
Author = {Avinun, R and Israel, S and Knodt, AR and Hariri,
AR},
Title = {Little evidence for associations between the Big Five
personality traits and variability in brain gray or white
matter.},
Journal = {NeuroImage},
Volume = {220},
Pages = {117092},
Year = {2020},
Month = {October},
Abstract = {Attempts to link the Big Five personality traits of
Openness-to-Experience, Conscientiousness, Extraversion,
Agreeableness, and Neuroticism with variability in
trait-like features of brain structure have produced
inconsistent results. Small sample sizes and heterogeneous
methodology have been suspected in driving these
inconsistencies. Here, using data collected from 1,107
university students (636 women, mean age
19.69 ± 1.24 years), representing the largest
sample to date of unrelated individuals, we tested for
associations between the Big Five personality traits and
measures of cortical thickness and surface area, subcortical
volume, and white matter microstructural integrity. In
addition to replication analyses based on a prior study, we
conducted exploratory whole-brain analyses. Four
supplementary analyses were also conducted to examine 1)
possible associations with lower-order facets of
personality; 2) modulatory effects of sex; 3) effect of
controlling for non-target personality traits; and 4)
parcellation scheme effects. Our analyses failed to identify
significant associations between the Big Five personality
traits and brain morphometry, except for a weak association
between greater surface area of the superior temporal gyrus
and lower conscientiousness scores. As the latter
association is not supported by previous studies, it should
be treated with caution. Our supplementary analyses mirrored
these predominantly null findings, suggesting they were not
substantively biased by our analytic choices. Collectively,
these results indicate that if there are associations
between the Big Five personality traits and brain structure,
they are likely of very small effect size and will require
very large samples for reliable detection.},
Doi = {10.1016/j.neuroimage.2020.117092},
Key = {fds364219}
}
@article{fds350143,
Author = {Elliott, ML and Knodt, AR and Ireland, D and Morris, ML and Poulton, R and Ramrakha, S and Sison, ML and Moffitt, TE and Caspi, A and Hariri,
AR},
Title = {What Is the Test-Retest Reliability of Common
Task-Functional MRI Measures? New Empirical Evidence and a
Meta-Analysis.},
Journal = {Psychological science},
Volume = {31},
Number = {7},
Pages = {792-806},
Year = {2020},
Month = {July},
Abstract = {Identifying brain biomarkers of disease risk is a growing
priority in neuroscience. The ability to identify meaningful
biomarkers is limited by measurement reliability; unreliable
measures are unsuitable for predicting clinical outcomes.
Measuring brain activity using task functional MRI (fMRI) is
a major focus of biomarker development; however, the
reliability of task fMRI has not been systematically
evaluated. We present converging evidence demonstrating poor
reliability of task-fMRI measures. First, a meta-analysis of
90 experiments (<i>N</i> = 1,008) revealed poor overall
reliability-mean intraclass correlation coefficient (ICC) =
.397. Second, the test-retest reliabilities of activity in a
priori regions of interest across 11 common fMRI tasks
collected by the Human Connectome Project (<i>N</i> = 45)
and the Dunedin Study (<i>N</i> = 20) were poor (ICCs =
.067-.485). Collectively, these findings demonstrate that
common task-fMRI measures are not currently suitable for
brain biomarker discovery or for individual-differences
research. We review how this state of affairs came to be and
highlight avenues for improving task-fMRI
reliability.},
Doi = {10.1177/0956797620916786},
Key = {fds350143}
}
@article{fds364220,
Author = {Baranger, DAA and Few, LR and Sheinbein, DH and Agrawal, A and Oltmanns,
TF and Knodt, AR and Barch, DM and Hariri, AR and Bogdan,
R},
Title = {Borderline Personality Traits Are Not Correlated With Brain
Structure in Two Large Samples.},
Journal = {Biological psychiatry. Cognitive neuroscience and
neuroimaging},
Volume = {5},
Number = {7},
Pages = {669-677},
Year = {2020},
Month = {July},
Abstract = {<h4>Background</h4>Borderline personality disorder is
associated with severe psychiatric presentations and has
been linked to variability in brain structure. Dimensional
models of borderline personality traits (BPTs) have become
influential; however, associations between BPTs and brain
structure remain poorly understood.<h4>Methods</h4>We tested
whether BPTs are associated with regional cortical
thickness, cortical surface area, and subcortical volumes
(n = 152 brain structure metrics) in data from the Duke
Neurogenetics Study (n = 1299) and Human Connectome Project
(n = 1099). Positive control analyses tested whether BPTs
are associated with related behaviors (e.g., suicidal
thoughts and behaviors, psychiatric diagnoses) and
experiences (e.g., adverse childhood experiences).<h4>Results</h4>While
BPTs were robustly associated with all positive control
measures, they were not significantly associated with any
brain structure metrics in the Duke Neurogenetics Study or
Human Connectome Project, or in a meta-analysis of both
samples. The strongest findings from the meta-analysis
showed a positive association between BPTs and volumes of
the left ventral diencephalon and thalamus (p values < .005
uncorrected, p values > .1 false discovery rate-corrected).
Contrasting high and low BPT decile groups (n = 552)
revealed no false discovery rate-significant associations
with brain structure.<h4>Conclusions</h4>We find replicable
evidence that BPTs are not associated with brain structure
despite being correlated with independent behavioral
measures. Prior reports linking brain morphology to
borderline personality disorder may be driven by factors
other than traits (e.g., severe presentations, comorbid
conditions, severe childhood adversity, or medication) or
reflect false positives. The etiology or consequences of
BPTs may not be attributable to brain structure measured via
magnetic resonance imaging. Future studies of BPTs will
require much larger sample sizes to detect these very small
effects.},
Doi = {10.1016/j.bpsc.2020.02.006},
Key = {fds364220}
}
@article{fds343722,
Author = {Puetz, VB and Viding, E and Gerin, MI and Pingault, J-B and Sethi, A and Knodt, AR and Radtke, SR and Brigidi, BD and Hariri, AR and McCrory,
E},
Title = {Investigating patterns of neural response associated with
childhood abuse v. childhood neglect - Corrigendum.},
Journal = {Psychological medicine},
Volume = {50},
Number = {8},
Pages = {1408},
Year = {2020},
Month = {June},
Abstract = {<h4>Background</h4>Childhood maltreatment is robustly
associated with increased risk of poor mental health outcome
and changes in brain function. The authors investigated
whether childhood experience of abuse (e.g. physical,
emotional and sexual abuse) and neglect (physical and
emotional deprivation) was differentially associated with
neural reactivity to threat.<h4>Methods</h4>Participants
were drawn from an existing study and allocated to one of
four groups based on self-report of childhood maltreatment
experience: individuals with childhood abuse experiences (n
= 70); individuals with childhood neglect experiences (n =
87); individuals with combined experience of childhood abuse
and neglect (n = 50); and non-maltreated individuals (n =
207) propensity score matched (PSM) on gender, age, IQ,
psychopathology and SES. Neural reactivity to facial cues
signalling threat was compared across groups, allowing the
differential effects associated with particular forms of
maltreatment experience to be isolated.<h4>Results</h4>Brain
imaging analyses indicated that while childhood abuse was
associated with heightened localised threat reactivity in
ventral amygdala, experiences of neglect were associated
with heightened reactivity in a distributed cortical
fronto-parietal network supporting complex social and
cognitive processing as well as in the dorsal amygdala.
Unexpectedly, combined experiences of abuse and neglect were
associated with hypo-activation in several higher-order
cortical regions as well as the amygdala.<h4>Conclusions</h4>Different
forms of childhood maltreatment exert differential effects
in neural threat reactivity: while the effects of abuse are
more focal, the effects of neglect and combined experiences
of abuse are more distributed. These findings are relevant
for understanding the range of psychiatric outcomes
following childhood maltreatment and have implications for
intervention.},
Doi = {10.1017/s0033291719001752},
Key = {fds343722}
}
@article{fds347193,
Author = {Baranger, DAA and Demers, CH and Elsayed, NM and Knodt, AR and Radtke,
SR and Desmarais, A and Few, LR and Agrawal, A and Heath, AC and Barch, DM and Squeglia, LM and Williamson, DE and Hariri, AR and Bogdan,
R},
Title = {Convergent Evidence for Predispositional Effects of Brain
Gray Matter Volume on Alcohol Consumption.},
Journal = {Biological psychiatry},
Volume = {87},
Number = {7},
Pages = {645-655},
Year = {2020},
Month = {April},
Abstract = {<h4>Background</h4>Alcohol use has been reliably associated
with smaller subcortical and cortical regional gray matter
volumes (GMVs). Whether these associations reflect shared
predisposing risk factors or causal consequences of alcohol
use remains poorly understood.<h4>Methods</h4>Data came from
3 neuroimaging samples (N = 2423), spanning childhood or
adolescence to middle age, with prospective or family-based
data. First, we identified replicable GMV correlates of
alcohol use. Next, we used family-based and longitudinal
data to test whether these associations may plausibly
reflect a predispositional liability for alcohol use or a
causal consequence of alcohol use. Finally, we used
heritability, gene-set enrichment, and transcriptome-wide
association study approaches to evaluate whether genome-wide
association study-defined genomic risk for alcohol
consumption is enriched for genes that are preferentially
expressed in regions that were identified in our
neuroimaging analyses.<h4>Results</h4>Smaller right
dorsolateral prefrontal cortex (DLPFC) (i.e., middle and
superior frontal gyri) and insula GMVs were associated with
increased alcohol use across samples. Family-based and
prospective longitudinal data suggest that these
associations are genetically conferred and that DLPFC GMV
prospectively predicts future use and initiation. Genomic
risk for alcohol use was enriched in gene sets that were
preferentially expressed in the DLPFC and was associated
with replicable differential gene expression in the
DLPFC.<h4>Conclusions</h4>These data suggest that smaller
DLPFC and insula GMV plausibly represent genetically
conferred predispositional risk factors for, as opposed to
consequences of, alcohol use. DLPFC and insula GMV represent
promising biomarkers for alcohol-consumption liability and
related psychiatric and behavioral phenotypes.},
Doi = {10.1016/j.biopsych.2019.08.029},
Key = {fds347193}
}
@article{fds364147,
Author = {Wallace, GL and Richard, E and Peng, CS and Knodt, AR and Hariri,
AR},
Title = {Subclinical eating disorder traits are correlated with
cortical thickness in regions associated with food reward
and perception.},
Journal = {Brain imaging and behavior},
Volume = {14},
Number = {2},
Pages = {346-352},
Year = {2020},
Month = {April},
Abstract = {Behavioral traits associated with various forms of
psychopathology are conceptualized as dimensional, varying
from those present in a frank disorder to subclinical
expression. Demonstrating links between these behavioral
traits and neurobiological indicators, such as brain
structure, provides one form of validation for this view.
However, unlike behavioral dimensions associated with other
forms of psychopathology (e.g., autism spectrum disorder,
attention deficit hyperactivity disorder, antisocial
disorders), eating disorder traits have not been
investigated in this manner in spite of the potential that
such an approach has to elucidate etiological mechanisms.
Therefore, we examined for the first time neural
endophenotypes of Anorexia Nervosa and Bulimia via
dimensional traits (measured using the Eating Disorders
Inventory-3) in a large subclinical sample of young adults
(n = 456 and n = 247, respectively;
ages = 18-22 years) who each provided a structural
magnetic resonance imaging scan. Cortical thickness was
quantified at 81,924 vertices across the cortical surface.
We found: 1) increasing eating disorder traits correlated
with thinner cortex in the insula and orbitofrontal cortex,
among other regions, and 2) using these regions as seeds,
increasing eating disorder trait scores negatively modulated
structural covariance between these seed regions and other
cortical regions linked to regulatory and sensorimotor
functions (e.g., frontal and temporal cortices). These
findings parallel those found in the clinical literature
(i.e., thinner cortex in these food-related regions in
individuals with eating disorders) and therefore provide
evidence supporting the dimensional view of behavioral
traits associated with eating disorders. Extending this
approach to genetic and neuroimaging genetics studies holds
promise to inform etiology.},
Doi = {10.1007/s11682-018-0007-x},
Key = {fds364147}
}
@article{fds364971,
Author = {Caspi, A and Houts, RM and Ambler, A and Danese, A and Elliott, ML and Hariri, A and Harrington, H and Hogan, S and Poulton, R and Ramrakha, S and Rasmussen, LJH and Reuben, A and Richmond-Rakerd, L and Sugden, K and Wertz, J and Williams, BS and Moffitt, TE},
Title = {Longitudinal Assessment of Mental Health Disorders and
Comorbidities Across 4 Decades Among Participants in the
Dunedin Birth Cohort Study.},
Journal = {JAMA network open},
Volume = {3},
Number = {4},
Pages = {e203221},
Year = {2020},
Month = {April},
Abstract = {<h4>Importance</h4>Mental health professionals typically
encounter patients at 1 point in patients' lives. This
cross-sectional window understandably fosters focus on the
current presenting diagnosis. Research programs, treatment
protocols, specialist clinics, and specialist journals are
oriented to presenting diagnoses, on the assumption that
diagnosis informs about causes and prognosis. This study
tests an alternative hypothesis: people with mental
disorders experience many different kinds of disorders
across diagnostic families, when followed for 4
decades.<h4>Objective</h4>To describe mental disorder life
histories across the first half of the life
course.<h4>Design, setting, and participants</h4>This cohort
study involved participants born in New Zealand from 1972 to
1973 who were enrolled in the population-representative
Dunedin Study. Participants were observed from birth to age
45 years (until April 2019). Data were analyzed from May
2019 to January 2020.<h4>Main outcomes and
measures</h4>Diagnosed impairing disorders were assessed 9
times from ages 11 to 45 years. Brain function was assessed
through neurocognitive examinations conducted at age 3
years, neuropsychological testing during childhood and
adulthood, and midlife neuroimaging-based brain
age.<h4>Results</h4>Of 1037 original participants (535 male
[51.6%]), 1013 had mental health data available. The
proportions of participants meeting the criteria for a
mental disorder were as follows: 35% (346 of 975) at ages 11
to 15 years, 50% (473 of 941) at age 18 years, 51% (489 of
961) at age 21 years, 48% (472 of 977) at age 26 years, 46%
(444 of 969) at age 32 years, 45% (429 of 955) at age 38
years, and 44% (407 of 927) at age 45 years. The onset of
the disorder occurred by adolescence for 59% of participants
(600 of 1013), eventually affecting 86% of the cohort (869
of 1013) by midlife. By age 45 years, 85% of participants
(737 of 869) with a disorder had accumulated comorbid
diagnoses. Participants with adolescent-onset disorders
subsequently presented with disorders at more past-year
assessments (r = 0.71; 95% CI, 0.68 to 0.74;
P < .001) and met the criteria for more diverse
disorders (r = 0.64; 95% CI, 0.60 to 0.67;
P < .001). Confirmatory factor analysis summarizing
mental disorder life histories across 4 decades identified a
general factor of psychopathology, the p-factor.
Longitudinal analyses showed that high p-factor scores
(indicating extensive mental disorder life histories) were
antedated by poor neurocognitive functioning at age 3 years
(r = -0.18; 95% CI, -0.24 to -0.12; P < .001), were
accompanied by childhood-to-adulthood cognitive decline
(r = -0.11; 95% CI, -0.17 to -0.04; P < .001), and
were associated with older brain age at midlife
(r = 0.14; 95% CI, 0.07 to 0.20; P < .001).<h4>Conclusions
and relevance</h4>These findings suggest that mental
disorder life histories shift among different successive
disorders. Data from the present study, alongside nationwide
data from Danish health registers, inform a life-course
perspective on mental disorders. This perspective cautions
against overreliance on diagnosis-specific research and
clinical protocols.},
Doi = {10.1001/jamanetworkopen.2020.3221},
Key = {fds364971}
}
@article{fds344832,
Author = {Avinun, R and Nevo, A and Radtke, SR and Brigidi, BD and Hariri,
AR},
Title = {Divergence of an association between depressive symptoms and
a dopamine polygenic score in Caucasians and
Asians.},
Journal = {European archives of psychiatry and clinical
neuroscience},
Volume = {270},
Number = {2},
Pages = {229-235},
Year = {2020},
Month = {March},
Abstract = {A recent study reported a negative association between a
putatively functional dopamine (DA) polygenic score,
indexing higher levels of DA signaling, and depressive
symptoms. We attempted to replicate this association using
data from the Duke Neurogenetics Study. Our replication
attempt was made in a subsample of 520 non-Hispanic
Caucasian volunteers (277 women, mean age
19.78 ± 1.24 years). The DA polygenic score was based
on the following five loci: rs27072 (SLC6A3/DAT1), rs4532
(DRD1), rs1800497 (DRD2/ANKK1), rs6280 (DRD3), and rs4680
(COMT). Because the discovery sample in the original study
consisted mostly of Asian participants, we also conducted a
post hoc analysis in a smaller subsample of Asian volunteers
(N = 316, 179 women, mean age 19.61 ± 1.32 years).
In the primary sample of non-Hispanic Caucasians, a linear
regression analysis controlling for sex, age, socioeconomic
status (SES), body mass index, genetic ancestry, and both
early and recent life stress, revealed that higher DA
polygenic scores were associated with higher self-reported
symptoms of depression. This was in contrast to the original
association of higher DA polygenic scores and lower
depressive symptoms. However, the direction of the
association in our Asian subsample was consistent with this
original finding. Our results also suggested that compared
to the Asian subsample, the non-Hispanic Caucasian subsample
was characterized by higher SES, lower early and recent life
stress, and lower depressive symptoms. These differences may
have contributed to the observed divergence in associations.
Collectively, the current findings add to evidence that
specific genetic associations may differ between populations
and further encourage explicit modeling of race/ethnicity in
examining the polygenic nature of depressive symptoms and
depression.},
Doi = {10.1007/s00406-019-01040-x},
Key = {fds344832}
}
@article{fds364972,
Author = {Carlisi, CO and Moffitt, TE and Knodt, AR and Harrington, H and Ireland,
D and Melzer, TR and Poulton, R and Ramrakha, S and Caspi, A and Hariri,
AR and Viding, E},
Title = {Associations between life-course-persistent antisocial
behaviour and brain structure in a population-representative
longitudinal birth cohort.},
Journal = {The lancet. Psychiatry},
Volume = {7},
Number = {3},
Pages = {245-253},
Year = {2020},
Month = {March},
Abstract = {<h4>Background</h4>Studies with behavioural and
neuropsychological tests have supported the developmental
taxonomy theory of antisocial behaviour, which specifies
abnormal brain development as a fundamental aspect of
life-course-persistent antisocial behaviour, but no study
has characterised features of brain structure associated
with life-course-persistent versus adolescence-limited
trajectories, as defined by prospective data. We aimed to
determine whether life-course-persistent antisocial
behaviour is associated with neurocognitive abnormalities by
testing the hypothesis that it is also associated with brain
structure abnormalities.<h4>Methods</h4>We used structural
MRI data collected at 45 years of age from participants in
the Dunedin Study, a population-representative longitudinal
birth cohort of 1037 individuals born between April 1, 1972,
and March 31, 1973, in Dunedin, New Zealand, who were
resident in the province and who participated in the first
assessment at 3 years of age. Participants underwent MRI,
and mean global cortical surface area and cortical thickness
were extracted for each participant. Participants had been
previously subtyped as exhibiting life-course-persistent,
adolescence-limited, or no history of persistent antisocial
behaviour (ie, a low trajectory group) based on
informant-reported and self-reported conduct problems from
the ages of 7 years to 26 years. Study personnel who
processed the MRI images were masked to antisocial group
membership. We used linear estimated ordinary least squares
regressions to compare each antisocial trajectory group
(life-course persistent and adolescence limited) with the
low trajectory group to examine whether antisocial behaviour
was related to abnormalities in mean global surface area and
mean cortical thickness. Next, we used parcel-wise linear
regressions to identify antisocial trajectory group
differences in surface area and cortical thickness. All
results were controlled for sex and false discovery rate
corrected.<h4>Findings</h4>Data from 672 participants were
analysed, and 80 (12%) were classified as having
life-course-persistent antisocial behaviour, 151 (23%) as
having adolescence-limited antisocial behaviour, and 441
(66%) as having low antisocial behaviour. Individuals on the
life-course-persistent trajectory had a smaller mean surface
area (standardised β=-0·18 [95% CI -0·24 to -0·11];
p<0·0001) and lower mean cortical thickness (standardised
β=-0·10 [95% CI -0·19 to -0·02]; p=0·020) than did
those in the low group. Compared with the low group, the
life-course-persistent group had reduced surface area in 282
of 360 anatomically defined parcels and thinner cortex in 11
of 360 parcels encompassing circumscribed frontal and
temporal regions associated with executive function, affect
regulation, and motivation. Widespread differences in brain
surface morphometry were not observed for the
adolescence-limited group compared with either
non-antisocial behaviour or life-course-persistent
groups.<h4>Interpretation</h4>These analyses provide initial
evidence that differences in brain surface morphometry are
associated with life-course-persistent, but not
adolescence-limited, antisocial behaviour. As such, the
analyses are consistent with the developmental taxonomy
theory of antisocial behaviour and highlight the importance
of using prospective longitudinal data to define different
patterns of antisocial behaviour development.<h4>Funding</h4>US
National Institute on Aging, Health Research Council of New
Zealand, New Zealand Ministry of Business, Innovation and
Employment, UK Medical Research Council, Avielle Foundation,
and Wellcome Trust.},
Doi = {10.1016/s2215-0366(20)30002-x},
Key = {fds364972}
}
@article{fds364172,
Author = {Burr, DA and d'Arbeloff, T and Elliott, ML and Knodt, AR and Brigidi,
BD and Hariri, AR},
Title = {Functional connectivity predicts the dispositional use of
expressive suppression but not cognitive
reappraisal.},
Journal = {Brain and behavior},
Volume = {10},
Number = {2},
Pages = {e01493},
Year = {2020},
Month = {February},
Abstract = {<h4>Introduction</h4>Previous research has identified
specific brain regions associated with regulating emotion
using common strategies such as expressive suppression and
cognitive reappraisal. However, most research focuses on a
priori regions and directs participants how to regulate,
which may not reflect how people naturally regulate outside
the laboratory.<h4>Method</h4>Here, we used a data-driven
approach to investigate how individual differences in
distributed intrinsic functional brain connectivity predict
emotion regulation tendency outside the laboratory.
Specifically, we used connectome-based predictive modeling
to extract functional connections in the brain significantly
related to the dispositional use of suppression and
reappraisal. These edges were then used in a predictive
model and cross-validated in novel participants to identify
a neural signature that reflects individual differences in
the tendency to suppress and reappraise emotion.<h4>Results</h4>We
found a significant neural signature for the dispositional
use of suppression, but not reappraisal. Within this
whole-brain signature, the intrinsic connectivity of the
default mode network was most informative of suppression
tendency. In addition, the predictive performance of this
model was significant in males, but not females.<h4>Conclusion</h4>These
findings help inform how whole-brain networks of functional
connectivity characterize how people tend to regulate
emotion outside the laboratory.},
Doi = {10.1002/brb3.1493},
Key = {fds364172}
}
@article{fds364142,
Author = {Detloff, AM and Hariri, AR and Strauman, TJ},
Title = {Neural signatures of promotion versus prevention goal
priming: fMRI evidence for distinct cognitive-motivational
systems.},
Journal = {Personality neuroscience},
Volume = {3},
Pages = {e1},
Year = {2020},
Month = {February},
Abstract = {Regulatory focus theory (RFT) postulates two
cognitive-motivational systems for personal goal pursuit:
the promotion system, which is associated with ideal goals
(an individual's hopes, dreams, and aspirations), and the
prevention system, which is associated with ought goals (an
individual's duties, responsibilities, and obligations). The
two systems have been studied extensively in behavioral
research with reference to differences between promotion and
prevention goal pursuit as well as the consequences of
perceived attainment versus nonattainment within each
system. However, no study has examined the neural correlates
of each combination of goal domain and goal attainment
status. We used a rapid masked idiographic goal priming
paradigm and functional magnetic resonance imaging to
present individually selected promotion and prevention
goals, which participants had reported previously that they
were close to attaining ("match") or far from attaining
("mismatch"). Across the four priming conditions,
significant activations were observed in bilateral insula
(Brodmann area (BA) 13) and visual association cortex (BA
18/19). Promotion priming discriminantly engaged left
prefrontal cortex (BA 9), whereas prevention priming
discriminantly engaged right prefrontal cortex (BA 8/9).
Activation in response to promotion goal priming was also
correlated with an individual difference measure of
perceived success in promotion goal attainment. Our findings
extend the construct validity of RFT by showing that the two
systems postulated by RFT, under conditions of both
attainment and nonattainment, have shared and distinct
neural correlates that interface logically with established
network models of self-regulatory cognition.},
Doi = {10.1017/pen.2019.13},
Key = {fds364142}
}
@article{fds364134,
Author = {Lee, MR and Shin, JH and Deschaine, S and Daurio, AM and Stangl, BL and Yan, J and Ramchandani, VA and Schwandt, ML and Grodin, EN and Momenan,
R and Corral-Frias, NS and Hariri, AR and Bogdan, R and Alvarez, VA and Leggio, L},
Title = {A role for the CD38 rs3796863 polymorphism in alcohol
and monetary reward: evidence from CD38 knockout mice and
alcohol self-administration, [11C]-raclopride binding, and
functional MRI in humans.},
Journal = {The American journal of drug and alcohol
abuse},
Volume = {46},
Number = {2},
Pages = {167-179},
Year = {2020},
Month = {January},
Abstract = {<i>Background</i>: Cluster of differentiation 38 (CD38) is a
transmembrane protein expressed in dopaminergic reward
pathways in the brain, including the nucleus accumbens
(NAc). The GG genotype of a common single nucleotide
polymorphism (SNP) within <i>CD38</i>, rs3796863, is
associated with increased social reward.<i>Objective</i>:
Examine whether <i>CD38</i> rs3796863 and <i>Cd38</i>
knockout (KO) are associated with reward-related neural and
behavioral phenotypes.<i>Methods</i>: Data from four
independent human studies were used to test whether
rs3796863 genotype is associated with: (1) intravenous
alcohol self-administration (n = 64, 30 females), (2)
alcohol-stimulated dopamine (DA) release measured using
<sup>11</sup>C-raclopride positron emission tomography
(n = 22 men), (3) ventral striatum (VS) response to
positive feedback measured using a card guessing functional
magnetic resonance imaging (fMRI) paradigm (n = 531, 276
females), and (4) resting state functional connectivity
(rsfc) of the VS (n = 51, 26 females). In a fifth study,
we used a mouse model to examine whether <i>cd38</i>
knockout influences stimulated DA release in the NAc core
and dorsal striatum using fast-scanning cyclic
voltammetry.<i>Results</i>: Relative to T allele carriers, G
homozygotes at rs3796863 within <i>CD38</i> were
characterized by greater alcohol self-administration,
alcohol-stimulated dopamine release, VS response to positive
feedback, and rsfc between the VS and anterior cingulate
cortex. High-frequency stimulation reduced DA release among
<i>Cd38</i> KO mice had reduced dopamine release in the
NAc.<i>Conclusion</i>: Converging evidence suggests that
<i>CD38</i> rs3796863 genotype may increase DA-related
reward response and alcohol consumption.},
Doi = {10.1080/00952990.2019.1638928},
Key = {fds364134}
}
@article{fds346711,
Author = {Farber, MJ and Kim, MJ and Knodt, AR and Hariri, AR},
Title = {Maternal overprotection in childhood is associated with
amygdala reactivity and structural connectivity in
adulthood.},
Journal = {Developmental cognitive neuroscience},
Volume = {40},
Pages = {100711},
Year = {2019},
Month = {December},
Abstract = {Recently, we reported that variability in early-life
caregiving experiences maps onto individual differences in
threat-related brain function. Here, we extend this work to
provide further evidence that subtle variability in specific
features of early caregiving shapes structural and
functional connectivity between the amygdala and medial
prefrontal cortex (mPFC) in a cohort of 312 young adult
volunteers. Multiple regression analyses revealed that
participants who reported higher maternal overprotection
exhibited increased amygdala reactivity to explicit signals
of interpersonal threat but not implicit signals of broad
environmental threat. While amygdala functional connectivity
with regulatory regions of the mPFC was not significantly
associated with maternal overprotection, participants who
reported higher maternal overprotection exhibited relatively
decreased structural integrity of the uncinate fasciculus
(UF), a white matter tract connecting these same brain
regions. There were no significant associations between
structural or functional brain measures and either maternal
or paternal care ratings. These findings suggest that an
overprotective maternal parenting style during childhood is
associated with later functional and structural alterations
of brain regions involved in generating and regulating
responses to threat.},
Doi = {10.1016/j.dcn.2019.100711},
Key = {fds346711}
}
@article{fds346872,
Author = {Wetherill, L and Lai, D and Johnson, EC and Anokhin, A and Bauer, L and Bucholz, KK and Dick, DM and Hariri, AR and Hesselbrock, V and Kamarajan, C and Kramer, J and Kuperman, S and Meyers, JL and Nurnberger, JI and Schuckit, M and Scott, DM and Taylor, RE and Tischfield, J and Porjesz, B and Goate, AM and Edenberg, HJ and Foroud,
T and Bogdan, R and Agrawal, A},
Title = {ERRATUM: Genome-wide association study identifies loci
associated with liability to alcohol and drug dependence
that is associated with variability in reward-related
ventral striatum activity in African- and
European-Americans.},
Journal = {Genes, brain, and behavior},
Volume = {18},
Number = {8},
Pages = {e12608},
Year = {2019},
Month = {November},
Doi = {10.1111/gbb.12608},
Key = {fds346872}
}
@article{fds364148,
Author = {Avinun, R and Hariri, AR},
Title = {A polygenic score for body mass index is associated with
depressive symptoms via early life stress: Evidence for
gene-environment correlation.},
Journal = {Journal of psychiatric research},
Volume = {118},
Pages = {9-13},
Year = {2019},
Month = {November},
Abstract = {Increasing childhood obesity rates are associated with not
only adverse physical, but also mental health outcomes,
including depression. These negative outcomes may be caused
and/or exacerbated by the bullying and shaming overweight
individuals experience. As body mass index (BMI) can be
highly heritable, we hypothesized that a genetic risk for
higher BMI, will predict higher early life stress (ELS),
which in turn will predict higher depressive symptoms in
adulthood. Such a process will reflect an evocative
gene-environment correlation (rGE) wherein an individual's
genetically influenced phenotype evokes a reaction from the
environment that subsequently shapes the individual's
health. We modeled genetic risk using a polygenic score of
BMI derived from a recent large GWAS meta-analysis.
Self-reports were used for the assessment of ELS and
depressive symptoms in adulthood. The discovery sample
consisted of 524 non-Hispanic Caucasian university students
from the Duke Neurogenetics Study (DNS; 278 women, mean age
19.78 ± 1.23 years) and the independent replication
sample consisted of 5930 white British individuals from the
UK biobank (UKB; 3128 women, mean age 62.66 ± 7.38
years). A significant mediation effect was found in the DNS
(indirect effect = 0.207, bootstrapped SE = .10,
bootstrapped 95% CI: 0.014 to 0.421), and then replicated in
the UKB (indirect effect = 0.04, bootstrapped
SE = .01, bootstrapped 95% CI: 0.018 to 0.066). Higher
BMI polygenic scores predicted higher ELS, which in turn
predicted higher depressive symptoms. Our findings suggest
that evocative rGE may contribute to weight-related mental
health problems and stress the need for interventions that
aim to reduce weight bias, specifically during
childhood.},
Doi = {10.1016/j.jpsychires.2019.08.008},
Key = {fds364148}
}
@article{fds364973,
Author = {Rasmussen, LJH and Caspi, A and Ambler, A and Broadbent, JM and Cohen,
HJ and d'Arbeloff, T and Elliott, M and Hancox, RJ and Harrington, H and Hogan, S and Houts, R and Ireland, D and Knodt, AR and Meredith-Jones,
K and Morey, MC and Morrison, L and Poulton, R and Ramrakha, S and Richmond-Rakerd, L and Sison, ML and Sneddon, K and Thomson, WM and Hariri, AR and Moffitt, TE},
Title = {Association of Neurocognitive and Physical Function With
Gait Speed in Midlife.},
Journal = {JAMA Netw Open},
Volume = {2},
Number = {10},
Pages = {e1913123},
Year = {2019},
Month = {October},
Abstract = {IMPORTANCE: Gait speed is a well-known indicator of risk of
functional decline and mortality in older adults, but little
is known about the factors associated with gait speed
earlier in life. OBJECTIVES: To test the hypothesis that
slow gait speed reflects accelerated biological aging at
midlife, as well as poor neurocognitive functioning in
childhood and cognitive decline from childhood to midlife.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study uses
data from the Dunedin Multidisciplinary Health and
Development Study, a population-based study of a
representative 1972 to 1973 birth cohort in New Zealand that
observed participants to age 45 years (until April 2019).
Data analysis was performed from April to June 2019.
EXPOSURES: Childhood neurocognitive functions and
accelerated aging, brain structure, and concurrent physical
and cognitive functions in adulthood. MAIN OUTCOMES AND
MEASURES: Gait speed at age 45 years, measured under 3
walking conditions: usual, dual task, and maximum gait
speeds. RESULTS: Of the 1037 original participants (91% of
eligible births; 535 [51.6%] male), 997 were alive at age 45
years, of whom 904 (90.7%) had gait speed measured (455
[50.3%] male; 93% white). The mean (SD) gait speeds were
1.30 (0.17) m/s for usual gait, 1.16 (0.23) m/s for dual
task gait, and 1.99 (0.29) m/s for maximum gait. Adults with
more physical limitations (standardized regression
coefficient [β], -0.27; 95% CI, -0.34 to -0.21;
P < .001), poorer physical functions (ie, weak grip
strength [β, 0.36; 95% CI, 0.25 to 0.46], poor balance [β,
0.28; 95% CI, 0.21 to 0.34], poor visual-motor coordination
[β, 0.24; 95% CI, 0.17 to 0.30], and poor performance on
the chair-stand [β, 0.34; 95% CI, 0.27 to 0.40] or 2-minute
step tests [β, 0.33; 95% CI, 0.27 to 0.39]; all
P < .001), accelerated biological aging across multiple
organ systems (β, -0.33; 95% CI, -0.40 to -0.27;
P < .001), older facial appearance (β, -0.25; 95% CI,
-0.31 to -0.18; P < .001), smaller brain volume (β,
0.15; 95% CI, 0.06 to 0.23; P < .001), more cortical
thinning (β, 0.09; 95% CI, 0.02 to 0.16; P = .01),
smaller cortical surface area (β, 0.13; 95% CI, 0.04 to
0.21; P = .003), and more white matter hyperintensities
(β, -0.09; 95% CI, -0.15 to -0.02; P = .01) had slower
gait speed. Participants with lower IQ in midlife (β, 0.38;
95% CI, 0.32 to 0.44; P < .001) and participants who
exhibited cognitive decline from childhood to adulthood (β,
0.10; 95% CI, 0.04 to 0.17; P < .001) had slower gait at
age 45 years. Those with poor neurocognitive functioning as
early as age 3 years had slower gait in midlife (β, 0.26;
95% CI, 0.20 to 0.32; P < .001). CONCLUSIONS AND
RELEVANCE: Adults' gait speed is associated with more than
geriatric functional status; it is also associated with
midlife aging and lifelong brain health.},
Doi = {10.1001/jamanetworkopen.2019.13123},
Key = {fds364973}
}
@article{fds364149,
Author = {Avinun, R and Nevo, A and Knodt, AR and Elliott, ML and Hariri,
AR},
Title = {A genome-wide association study-derived polygenic score for
interleukin-1β is associated with hippocampal volume in two
samples.},
Journal = {Human brain mapping},
Volume = {40},
Number = {13},
Pages = {3910-3917},
Year = {2019},
Month = {September},
Abstract = {Accumulating research suggests that the pro-inflammatory
cytokine interleukin-1β (IL-1β) has a modulatory effect on
the hippocampus, a brain structure important for learning
and memory as well as linked with both psychiatric and
neurodegenerative disorders. Here, we used an imaging
genetics strategy to test an association between an IL-1β
polygenic score and hippocampal volume in two independent
samples. Our polygenic score was derived using summary
statistics from a recent genome-wide association study of
circulating cytokines that included IL-1β (N = 3,309). In
the first sample of 512 non-Hispanic Caucasian university
students (274 women, mean age 19.78 ± 1.24 years) from
the Duke Neurogenetics Study, we identified a significant
positive correlation between IL-1β polygenic scores and
hippocampal volume. This positive association was
successfully replicated in a second sample of 7,960 white
British volunteers (4,158 women, mean age 62.63 ± 7.45
years) from the UK Biobank. Our results lend further support
in humans, to the link between IL-1β and the structure of
the hippocampus.},
Doi = {10.1002/hbm.24639},
Key = {fds364149}
}
@article{fds345489,
Author = {Lam, M and Hill, WD and Trampush, JW and Yu, J and Knowles, E and Davies,
G and Stahl, E and Huckins, L and Liewald, DC and Djurovic, S and Melle, I and Sundet, K and Christoforou, A and Reinvang, I and DeRosse, P and Lundervold, AJ and Steen, VM and Espeseth, T and Räikkönen, K and Widen, E and Palotie, A and Eriksson, JG and Giegling, I and Konte, B and Hartmann, AM and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier, W and Chiba-Falek, O and Attix, DK and Need, AC and Cirulli, ET and Voineskos, AN and Stefanis, NC and Avramopoulos, D and Hatzimanolis, A and Arking, DE and Smyrnis, N and Bilder, RM and Freimer, NA and Cannon, TD and London, E and Poldrack, RA and Sabb, FW and Congdon, E and Conley, ED and Scult, MA and Dickinson, D and Straub, RE and Donohoe, G and Morris, D and Corvin, A and Gill, M and Hariri, AR and Weinberger, DR and Pendleton, N and Bitsios, P and Rujescu, D and Lahti,
J and Le Hellard and S and Keller, MC and Andreassen, OA and Deary, IJ and Glahn, DC and Malhotra, AK and Lencz, T},
Title = {Pleiotropic Meta-Analysis of Cognition, Education, and
Schizophrenia Differentiates Roles of Early
Neurodevelopmental and Adult Synaptic Pathways.},
Journal = {Am J Hum Genet},
Volume = {105},
Number = {2},
Pages = {334-350},
Year = {2019},
Month = {August},
Abstract = {Susceptibility to schizophrenia is inversely correlated with
general cognitive ability at both the phenotypic and the
genetic level. Paradoxically, a modest but consistent
positive genetic correlation has been reported between
schizophrenia and educational attainment, despite the strong
positive genetic correlation between cognitive ability and
educational attainment. Here we leverage published
genome-wide association studies (GWASs) in cognitive
ability, education, and schizophrenia to parse biological
mechanisms underlying these results. Association analysis
based on subsets (ASSET), a pleiotropic meta-analytic
technique, allowed jointly associated loci to be identified
and characterized. Specifically, we identified subsets of
variants associated in the expected ("concordant") direction
across all three phenotypes (i.e., greater risk for
schizophrenia, lower cognitive ability, and lower
educational attainment); these were contrasted with variants
that demonstrated the counterintuitive ("discordant")
relationship between education and schizophrenia (i.e.,
greater risk for schizophrenia and higher educational
attainment). ASSET analysis revealed 235 independent loci
associated with cognitive ability, education, and/or
schizophrenia at p < 5 × 10-8. Pleiotropic analysis
successfully identified more than 100 loci that were not
significant in the input GWASs. Many of these have been
validated by larger, more recent single-phenotype GWASs.
Leveraging the joint genetic correlations of cognitive
ability, education, and schizophrenia, we were able to
dissociate two distinct biological mechanisms-early
neurodevelopmental pathways that characterize concordant
allelic variation and adulthood synaptic pruning
pathways-that were linked to the paradoxical positive
genetic association between education and schizophrenia.
Furthermore, genetic correlation analyses revealed that
these mechanisms contribute not only to the etiopathogenesis
of schizophrenia but also to the broader biological
dimensions implicated in both general health outcomes and
psychiatric illness.},
Doi = {10.1016/j.ajhg.2019.06.012},
Key = {fds345489}
}
@article{fds343721,
Author = {Lai, D and Wetherill, L and Bertelsen, S and Carey, CE and Kamarajan, C and Kapoor, M and Meyers, JL and Anokhin, AP and Bennett, DA and Bucholz,
KK and Chang, KK and De Jager and PL and Dick, DM and Hesselbrock, V and Kramer, J and Kuperman, S and Nurnberger, JI and Raj, T and Schuckit, M and Scott, DM and Taylor, RE and Tischfield, J and Hariri, AR and Edenberg,
HJ and Agrawal, A and Bogdan, R and Porjesz, B and Goate, AM and Foroud,
T},
Title = {Genome-wide association studies of alcohol dependence,
DSM-IV criterion count and individual criteria.},
Journal = {Genes, brain, and behavior},
Volume = {18},
Number = {6},
Pages = {e12579},
Year = {2019},
Month = {July},
Abstract = {Genome-wide association studies (GWAS) of alcohol dependence
(AD) have reliably identified variation within alcohol
metabolizing genes (eg, ADH1B) but have inconsistently
located other signals, which may be partially attributable
to symptom heterogeneity underlying the disorder. We
conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD
criterion count (secondary analysis), and individual
dependence criteria (tertiary analysis) among 7418 (1121
families) European American (EA) individuals from the
Collaborative Study on the Genetics of Alcoholism (COGA).
Trans-ancestral meta-analyses combined these results with
data from 3175 (585 families) African-American (AA)
individuals from COGA. In the EA GWAS, three loci were
genome-wide significant: rs1229984 in ADH1B for AD criterion
count (P = 4.16E-11) and Desire to cut drinking (P =
1.21E-11); rs188227250 (chromosome 8, Drinking more than
intended, P = 6.72E-09); rs1912461 (chromosome 15, Time
spent drinking, P = 1.77E-08). In the trans-ancestral
meta-analysis, rs1229984 was associated with multiple
phenotypes and two additional loci were genome-wide
significant: rs61826952 (chromosome 1, DSM-IV AD, P =
8.42E-11); rs7597960 (chromosome 2, Time spent drinking, P =
1.22E-08). Associations with rs1229984 and rs18822750 were
replicated in independent datasets. Polygenic risk scores
derived from the EA GWAS of AD predicted AD in two EA
datasets (P < .01; 0.61%-1.82% of variance). Identified
novel variants (ie, rs1912461, rs61826952) were associated
with differential central evoked theta power (loss - gain; P
= .0037) and reward-related ventral striatum reactivity (P =
.008), respectively. This study suggests that studying
individual criteria may unveil new insights into the genetic
etiology of AD liability.},
Doi = {10.1111/gbb.12579},
Key = {fds343721}
}
@article{fds348913,
Author = {Elliott, ML and Belsky, DW and Anderson, K and Corcoran, DL and Ge, T and Knodt, A and Prinz, JA and Sugden, K and Williams, B and Ireland, D and Poulton, R and Caspi, A and Holmes, A and Moffitt, T and Hariri,
AR},
Title = {A Polygenic Score for Higher Educational Attainment is
Associated with Larger Brains.},
Journal = {Cerebral cortex (New York, N.Y. : 1991)},
Volume = {29},
Number = {8},
Pages = {3496-3504},
Year = {2019},
Month = {July},
Abstract = {People who score higher on intelligence tests tend to have
larger brains. Twin studies suggest the same genetic factors
influence both brain size and intelligence. This has led to
the hypothesis that genetics influence intelligence partly
by contributing to the development of larger brains. We
tested this hypothesis using four large imaging genetics
studies (combined N = 7965) with polygenic scores derived
from a genome-wide association study (GWAS) of educational
attainment, a correlate of intelligence. We conducted
meta-analysis to test associations among participants'
genetics, total brain volume (i.e., brain size), and
cognitive test performance. Consistent with previous
findings, participants with higher polygenic scores achieved
higher scores on cognitive tests, as did participants with
larger brains. Participants with higher polygenic scores
also had larger brains. We found some evidence that brain
size partly mediated associations between participants'
education polygenic scores and their cognitive test
performance. Effect sizes were larger in the
population-based samples than in the convenience-based
samples. Recruitment and retention of population-representative
samples should be a priority for neuroscience research.
Findings suggest promise for studies integrating GWAS
discoveries with brain imaging to understand neurobiology
linking genetics with cognitive performance.},
Doi = {10.1093/cercor/bhy219},
Key = {fds348913}
}
@article{fds364150,
Author = {Avinun, R and Nevo, A and Hariri, AR},
Title = {Genetic Risk for Rheumatoid Arthritis is Associated with
Increased Striatal Volume in Healthy Young
Adults.},
Journal = {Scientific reports},
Volume = {9},
Number = {1},
Pages = {10994},
Year = {2019},
Month = {July},
Abstract = {Rheumatoid arthritis (RA), an autoimmune disease, has
recently been associated with increased striatal volume and
decreased intracranial volume (ICV) in longstanding
patients. As inflammation has been shown to precede the
clinical diagnosis of RA and it is a known moderator of
neuro- and gliogenesis, we were interested in testing
whether these brain morphological changes appear before the
clinical onset of disease in healthy young adult volunteers,
as a function of relative genetic risk for RA. Genetic and
structural MRI data were available for 516 healthy
non-Hispanic Caucasian university students (275 women, mean
age 19.78 ± 1.24 years). Polygenic risk scores were
computed for each individual based on a genome-wide
association study of RA, so that higher scores indicated
higher risk. Striatal volume (sum of caudate, putamen, and
nucleus accumbens volumes) and ICV were derived for each
individual from high-resolution T1-weighted images. After
controlling for sex, age, genetic components of ethnicity,
socioeconomic status, and depressive symptoms, we found that
higher RA polygenic risk scores were associated with
increased striatal volume, but not decreased ICV. Our
findings suggest that increased striatal volume may be
linked to processes that precede disease onset, such as
inflammation, while decreased ICV may relate to disease
progression.},
Doi = {10.1038/s41598-019-47505-w},
Key = {fds364150}
}
@article{fds364135,
Author = {Wetherill, L and Lai, D and Johnson, EC and Anokhin, A and Bauer, L and Bucholz, KK and Dick, DM and Hariri, AR and Hesselbrock, V and Kamarajan, C and Kramer, J and Kuperman, S and Meyers, JL and Nurnberger, JI and Schuckit, M and Scott, DM and Taylor, RE and Tischfield, J and Porjesz, B and Goate, AM and Edenberg, HJ and Foroud,
T and Bogdan, R and Agrawal, A},
Title = {Genome-wide association study identifies loci associated
with liability to alcohol and drug dependence that is
associated with variability in reward-related ventral
striatum activity in African- and European-Americans.},
Journal = {Genes, brain, and behavior},
Volume = {18},
Number = {6},
Pages = {e12580},
Year = {2019},
Month = {July},
Abstract = {Genetic influences on alcohol and drug dependence partially
overlap, however, specific loci underlying this overlap
remain unclear. We conducted a genome-wide association study
(GWAS) of a phenotype representing alcohol or illicit drug
dependence (ANYDEP) among 7291 European-Americans (EA; 2927
cases) and 3132 African-Americans (AA: 1315 cases)
participating in the family-based Collaborative Study on the
Genetics of Alcoholism. ANYDEP was heritable (h <sup>2</sup>
in EA = 0.60, AA = 0.37). The AA GWAS identified three
regions with genome-wide significant (GWS; P < 5E-08)
single nucleotide polymorphisms (SNPs) on chromosomes 3
(rs34066662, rs58801820) and 13 (rs75168521, rs78886294),
and an insertion-deletion on chromosome 5 (chr5:141988181).
No polymorphisms reached GWS in the EA. One GWS region
(chromosome 1: rs1890881) emerged from a trans-ancestral
meta-analysis (EA + AA) of ANYDEP, and was attributable
to alcohol dependence in both samples. Four genes (AA: CRKL,
DZIP3, SBK3; EA: P2RX6) and four sets of genes were
significantly enriched within biological pathways for
hemostasis and signal transduction. GWS signals did not
replicate in two independent samples but there was weak
evidence for association between rs1890881 and alcohol
intake in the UK Biobank. Among 118 AA and 481 EA
individuals from the Duke Neurogenetics Study, rs75168521
and rs1890881 genotypes were associated with variability in
reward-related ventral striatum activation. This study
identified novel loci for substance dependence and provides
preliminary evidence that these variants are also associated
with individual differences in neural reward reactivity.
Gene discovery efforts in non-European samples with distinct
patterns of substance use may lead to the identification of
novel ancestry-specific genetic markers of
risk.},
Doi = {10.1111/gbb.12580},
Key = {fds364135}
}
@article{fds364151,
Author = {Gerin, MI and Viding, E and Pingault, J-B and Puetz, VB and Knodt, AR and Radtke, SR and Brigidi, BD and Swartz, JR and Hariri, AR and McCrory,
EJ},
Title = {Heightened amygdala reactivity and increased stress
generation predict internalizing symptoms in adults
following childhood maltreatment.},
Journal = {Journal of child psychology and psychiatry, and allied
disciplines},
Volume = {60},
Number = {7},
Pages = {752-761},
Year = {2019},
Month = {July},
Abstract = {<h4>Background</h4>Childhood maltreatment is one of the most
potent predictors of future psychopathology, including
internalizing disorders. It remains unclear whether
heightened amygdala reactivity to threat and elevated stress
exposure may be implicated in the pathogenesis and
maintenance of internalizing disorders among individuals
with a history of childhood maltreatment.<h4>Methods</h4>Using
data from a sample of 1,144 young adults, we investigated
the contribution of baseline threat-related amygdala
reactivity and prospective major stressful life events to
internalizing symptoms severity 1 year later (on average)
in individuals with a history of maltreatment (n = 100)
and propensity score matched nonmaltreated peers
(n = 96).<h4>Results</h4>Even after stringently matching
for several potentially confounding variables - including
baseline internalizing symptoms, socioeconomic status and IQ
- childhood maltreatment status predicted increased amygdala
reactivity at baseline, elevated post-baseline exposure to
major stressful life events and internalizing symptoms at
follow-up. We also showed, for the first time, that amygdala
reactivity at baseline and also post-baseline exposure to
major stressful life events mediated the association between
a history of maltreatment and future internalizing
symptoms.<h4>Conclusions</h4>These findings provide support
for the view that maltreatment is a potent developmental
insult leading to long-lasting neurocognitive recalibrations
of the threat processing system. It is possible that such
alterations, over time, may impact mental health functioning
by compromising the ability to effectively negotiate
everyday challenges (stress susceptibility). These
alterations were not, however, found to sensitize an
individual to the impact of major stressful life events. The
results of this study also lend compelling support to the
view that increased psychiatric risk, in the context of
childhood maltreatment, follows from an increased propensity
to experience major stressful life events (stress
generation).},
Doi = {10.1111/jcpp.13041},
Key = {fds364151}
}
@article{fds364152,
Author = {Farber, MJ and Romer, AL and Kim, MJ and Knodt, AR and Elsayed, NM and Williamson, DE and Hariri, AR},
Title = {Paradoxical associations between familial affective
responsiveness, stress, and amygdala reactivity.},
Journal = {Emotion (Washington, D.C.)},
Volume = {19},
Number = {4},
Pages = {645-654},
Year = {2019},
Month = {June},
Abstract = {Studies of early life extremes such as trauma, abuse, and
neglect highlight the critical importance of quality
caregiving in the development of brain circuits supporting
emotional behavior and mental health. The impact of
normative variability in caregiving on such biobehavioral
processes, however, is poorly understood. Here, we provide
initial evidence that even subtle variability in normative
caregiving maps onto individual differences in
threat-related brain function and, potentially, associated
psychopathology in adolescence. Specifically, we report that
greater familial affective responsiveness is associated with
heightened amygdala reactivity to interpersonal threat,
particularly in adolescents having experienced relatively
low recent stress. These findings extend the literature on
the effects of caregiving extremes on brain function to
subtle, normative variability but suggest that presumably
protective factors may be associated with increased
risk-related amygdala reactivity. We consider these
paradoxical associations with regard to studies of basic
associative threat learning and further consider their
relevance for understanding potential effects of caregiving
on psychological development. (PsycINFO Database Record (c)
2019 APA, all rights reserved).},
Doi = {10.1037/emo0000467},
Key = {fds364152}
}
@article{fds364153,
Author = {Kim, MJ and Elliott, ML and d'Arbeloff, TC and Knodt, AR and Radtke, SR and Brigidi, BD and Hariri, AR},
Title = {Microstructural integrity of white matter moderates an
association between childhood adversity and adult trait
anger.},
Journal = {Aggressive behavior},
Volume = {45},
Number = {3},
Pages = {310-318},
Year = {2019},
Month = {May},
Abstract = {Amongst a number of negative life sequelae associated with
childhood adversity is the later expression of a higher
dispositional tendency to experience anger and frustration
to a wide range of situations (i.e., trait anger). We
recently reported that an association between childhood
adversity and trait anger is moderated by individual
differences in both threat-related amygdala activity and
executive control-related dorsolateral prefrontal cortex
(dlPFC) activity, wherein individuals with relatively low
amygdala and high dlPFC activity do not express higher trait
anger even when having experienced childhood adversity.
Here, we examine possible structural correlates of this
functional dynamic using diffusion magnetic resonance
imaging data from 647 young adult men and women volunteers.
Specifically, we tested whether the degree of white matter
microstructural integrity as indexed by fractional
anisotropy modulated the association between childhood
adversity and trait anger. Our analyses revealed that higher
microstructural integrity of multiple pathways was
associated with an attenuated link between childhood
adversity and adult trait anger. Amongst these pathways was
the uncinate fasciculus (UF; ΔR <sup>2</sup> = 0.01),
which not only provides a major anatomical link between the
amygdala and prefrontal cortex but also is associated with
individual differences in regulating negative emotion
through top-down cognitive reappraisal. These findings
suggest that higher microstructural integrity of distributed
white matter pathways including but not limited to the UF
may represent an anatomical foundation serving to buffer
against the expression of childhood adversity as later trait
anger, which is itself associated with multiple negative
health outcomes.},
Doi = {10.1002/ab.21820},
Key = {fds364153}
}
@article{fds342490,
Author = {Hariri, AR},
Title = {The Emerging Importance of the Cerebellum in Broad Risk for
Psychopathology.},
Journal = {Neuron},
Volume = {102},
Number = {1},
Pages = {17-20},
Year = {2019},
Month = {April},
Abstract = {Recent research has identified a single factor accounting
for broad risk to experience common forms of
psychopathology. Structural alterations of cerebellar
circuitry have emerged as a neural nexus of this broad risk,
highlighting the cerebellum's importance for executive
control.},
Doi = {10.1016/j.neuron.2019.02.031},
Key = {fds342490}
}
@article{fds364182,
Author = {Elliott, ML and Knodt, AR and Cooke, M and Kim, MJ and Melzer, TR and Keenan, R and Ireland, D and Ramrakha, S and Poulton, R and Caspi, A and Moffitt, TE and Hariri, AR},
Title = {General functional connectivity: Shared features of
resting-state and task fMRI drive reliable and heritable
individual differences in functional brain
networks.},
Journal = {NeuroImage},
Volume = {189},
Pages = {516-532},
Year = {2019},
Month = {April},
Abstract = {Intrinsic connectivity, measured using resting-state fMRI,
has emerged as a fundamental tool in the study of the human
brain. However, due to practical limitations, many studies
do not collect enough resting-state data to generate
reliable measures of intrinsic connectivity necessary for
studying individual differences. Here we present general
functional connectivity (GFC) as a method for leveraging
shared features across resting-state and task fMRI and
demonstrate in the Human Connectome Project and the Dunedin
Study that GFC offers better test-retest reliability than
intrinsic connectivity estimated from the same amount of
resting-state data alone. Furthermore, at equivalent scan
lengths, GFC displayed higher estimates of heritability than
resting-state functional connectivity. We also found that
predictions of cognitive ability from GFC generalized across
datasets, performing as well or better than resting-state or
task data alone. Collectively, our work suggests that GFC
can improve the reliability of intrinsic connectivity
estimates in existing datasets and, subsequently, the
opportunity to identify meaningful correlates of individual
differences in behavior. Given that task and resting-state
data are often collected together, many researchers can
immediately derive more reliable measures of intrinsic
connectivity through the adoption of GFC rather than solely
using resting-state data. Moreover, by better capturing
heritable variation in intrinsic connectivity, GFC
represents a novel endophenotype with broad applications in
clinical neuroscience and biomarker discovery.},
Doi = {10.1016/j.neuroimage.2019.01.068},
Key = {fds364182}
}
@article{fds364154,
Author = {Romer, AL and Su Kang and M and Nikolova, YS and Gearhardt, AN and Hariri,
AR},
Title = {Dopamine genetic risk is related to food addiction and body
mass through reduced reward-related ventral striatum
activity.},
Journal = {Appetite},
Volume = {133},
Pages = {24-31},
Year = {2019},
Month = {February},
Abstract = {The prevalence rate of obesity continues to rise in the
U.S., but effective treatment options remain elusive
resulting in increased emphasis on prevention. One such area
of prevention research capitalizes on the relatively novel
behavioral construct of food addiction, which has been
implicated in obesity. Food addiction reflects an
individual's propensity for compulsive eating despite
negative consequences, and shares not only symptoms with
both eating and substance use disorders but also genetic and
neural correlates within neural reward-circuitry modulated
by dopamine. Here, we examined associations between food
addiction scores, body mass index (BMI), reward-related
ventral striatum activity, and a polygenic score
approximating dopamine signaling in 115 non-Hispanic
Caucasian young adult university students. As predicted,
polygenic dopamine scores were related to ventral striatum
activity, which in turn was associated with higher food
addiction scores. In addition, food addiction was related to
BMI. An exploratory post-hoc path analysis further indicated
that polygenic scores were indirectly related to both food
addiction and BMI, in part, through ventral striatum
activity. Collectively, our results provide evidence
supporting the utility of food addiction in weight gain
prevention research by establishing links with known
risk-related neural and genetic biomarkers.},
Doi = {10.1016/j.appet.2018.09.010},
Key = {fds364154}
}
@article{fds346873,
Author = {Kim, MJ and Farber, MJ and Knodt, AR and Hariri, AR},
Title = {Corticolimbic circuit structure moderates an association
between early life stress and later trait
anxiety.},
Journal = {NeuroImage. Clinical},
Volume = {24},
Pages = {102050},
Year = {2019},
Month = {January},
Abstract = {Childhood adversity is associated with a wide range of
negative behavioral and neurodevelopmental consequences.
However, individuals vary substantially in their sensitivity
to such adversity. Here, we examined how individual
variability in structural features of the corticolimbic
circuit, which plays a key role in emotional reactivity,
moderates the association between childhood adversity and
later trait anxiety in 798 young adult university students.
Consistent with prior research, higher self-reported
childhood adversity was significantly associated with higher
self-reported trait anxiety. However, this association was
attenuated in participants with higher microstructural
integrity of the uncinate fasciculus and greater thickness
of the orbitofrontal cortex. These structural properties of
the corticolimbic circuit may capture a neural profile of
relative resiliency to early life stress, especially against
the negative effects of childhood adversity on later trait
anxiety.},
Doi = {10.1016/j.nicl.2019.102050},
Key = {fds346873}
}
@article{fds366148,
Author = {d'Arbeloff, T and Elliott, ML and Knodt, AR and Melzer, TR and Keenan,
R and Ireland, D and Ramrakha, S and Poulton, R and Anderson, T and Caspi,
A and Moffitt, TE and Hariri, AR},
Title = {White matter hyperintensities are common in midlife and
already associated with cognitive decline.},
Journal = {Brain communications},
Volume = {1},
Number = {1},
Pages = {fcz041},
Year = {2019},
Month = {January},
Abstract = {White matter hyperintensities proliferate as the brain ages
and are associated with increased risk for cognitive decline
as well as Alzheimer's disease and related dementias. As
such, white matter hyperintensities have been targeted as a
surrogate biomarker in intervention trials with older
adults. However, it is unclear at what stage of aging white
matter hyperintensities begin to relate to cognition and if
they may be a viable target for early prevention. In the
Dunedin Study, a population-representative cohort followed
since birth, we measured white matter hyperintensities in
843 45-year-old participants using T<sub>2</sub>-weighted
magnetic resonance imaging and we assessed cognitive decline
from childhood to midlife. We found that white matter
hyperintensities were common at age 45 and that white matter
hyperintensity volume was modestly associated with both
lower childhood (<i>ß</i> = -0.08, <i>P </i>=<i> </i>0.013)
and adult IQ (<i>ß</i>=-0.15, <i>P </i><<i> </i>0.001).
Moreover, white matter hyperintensity volume was associated
with greater cognitive decline from childhood to midlife
(<i>ß</i>=-0.09, <i>P </i><<i> </i>0.001). Our results
demonstrate that a link between white matter
hyperintensities and early signs of cognitive decline is
detectable decades before clinical symptoms of dementia
emerge. Thus, white matter hyperintensities may be a useful
surrogate biomarker for identifying individuals in midlife
at risk for future accelerated cognitive decline and
selecting participants for dementia prevention
trials.},
Doi = {10.1093/braincomms/fcz041},
Key = {fds366148}
}
@article{fds364132,
Author = {Knodt, AR and Burke, JR and Welsh-Bohmer, KA and Plassman, BL and Burns,
DK and Brannan, SK and Kukulka, M and Wu, J and Hariri,
AR},
Title = {Effects of pioglitazone on mnemonic hippocampal function: A
blood oxygen level-dependent functional magnetic resonance
imaging study in elderly adults.},
Journal = {Alzheimers Dement (N Y)},
Volume = {5},
Pages = {254-263},
Year = {2019},
Abstract = {INTRODUCTION: Mitochondrial dysfunction is implicated in the
pathophysiology of Alzheimer's disease (AD). Accordingly,
drugs that positively influence mitochondrial function are
being evaluated in delay-of-onset clinical trials with
at-risk individuals. Such ongoing clinical research can be
advanced by developing a better understanding of how these
drugs affect intermediate brain phenotypes associated with
both AD risk and pathophysiology. METHODS: Using a
randomized, parallel-group, placebo-controlled design in 55
healthy elderly volunteers, we explored the effects of oral,
low-dose pioglitazone, a thiazolidinedione with
promitochondrial effects, on hippocampal activity measured
with functional magnetic resonance imaging during the
encoding of novel face-name pairs. RESULTS: Compared with
placebo, 0.6 mg of pioglitazone (but not 2.1 mg, 3.9 mg,
or 6.0 mg) administered daily for 14 days was associated
with significant increases in right hippocampal activation
during encoding of novel face-name pairs at day 7 and day
14, relative to baseline. DISCUSSION: Our exploratory
analyses suggest that low-dose pioglitazone has measurable
effects on mnemonic brain function associated with AD risk
and pathophysiology.},
Doi = {10.1016/j.trci.2019.05.004},
Key = {fds364132}
}
@article{fds335689,
Author = {Sethi, A and McCrory, E and Puetz, V and Hoffmann, F and Knodt, AR and Radtke, SR and Brigidi, BD and Hariri, AR and Viding,
E},
Title = {Primary and Secondary Variants of Psychopathy in a Volunteer
Sample Are Associated With Different Neurocognitive
Mechanisms.},
Journal = {Biological psychiatry. Cognitive neuroscience and
neuroimaging},
Volume = {3},
Number = {12},
Pages = {1013-1021},
Publisher = {Elsevier BV},
Year = {2018},
Month = {December},
Abstract = {<h4>Background</h4>Recent work has indicated that there at
least two distinct subtypes of psychopathy. Primary
psychopathy is characterized by low anxiety and thought to
result from a genetic predisposition, whereas secondary
psychopathy is characterized by high anxiety and thought to
develop in response to environmental adversity. Primary
psychopathy is robustly associated with reduced neural
activation to others' emotions and, in particular, distress.
However, it has been proposed that the secondary
presentation has different neurocognitive
correlates.<h4>Methods</h4>Primary (n = 50), secondary
(n = 100), and comparison (n = 82) groups were drawn from
a large volunteer sample (N = 1444) using a quartile-split
approach across psychopathic trait (affective-interpersonal)
and anxiety measures. Participants performed a widely
utilized emotional face processing task during functional
magnetic resonance imaging.<h4>Results</h4>The primary group
showed reduced amygdala and insula activity in response to
fear. The secondary group did not differ from the comparison
group in these regions. Instead, the secondary group showed
reduced activity compared with the comparison group in other
areas, including the superior temporal sulcus/inferior
parietal lobe, thalamus, pallidum, and substantia nigra.
Both psychopathy groups also showed reduced activity in
response to fear in the anterior cingulate cortex. During
anger processing, the secondary group exhibited reduced
activity in the anterior cingulate cortex compared with the
primary group.<h4>Conclusions</h4>Distinct neural correlates
of fear processing characterize individuals with primary and
secondary psychopathy. The reduced neural response to fear
that characterizes individuals with the primary variant of
psychopathic traits is not observed in individuals with the
secondary presentation. The neurocognitive mechanisms
underpinning secondary psychopathy warrant further
systematic investigation.},
Doi = {10.1016/j.bpsc.2018.04.002},
Key = {fds335689}
}
@article{fds335682,
Author = {Lam, M and Trampush, JW and Yu, J and Knowles, E and Djurovic, S and Melle,
I and Sundet, K and Christoforou, A and Reinvang, I and DeRosse, P and Lundervold, AJ and Steen, VM and Espeseth, T and Räikkönen, K and Widen, E and Palotie, A and Eriksson, JG and Giegling, I and Konte, B and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier,
W and Chiba-Falek, O and Attix, DK and Need, AC and Cirulli, ET and Voineskos, AN and Stefanis, NC and Avramopoulos, D and Hatzimanolis,
A and Arking, DE and Smyrnis, N and Bilder, RM and Freimer, NA and Cannon,
TD and London, E and Poldrack, RA and Sabb, FW and Congdon, E and Conley,
ED and Scult, MA and Dickinson, D and Straub, RE and Donohoe, G and Morris,
D and Corvin, A and Gill, M and Hariri, AR and Weinberger, DR and Pendleton, N and Bitsios, P and Rujescu, D and Lahti, J and Hellard, SL and Keller, MC and Andreassen, OA and Glahn, DC and Malhotra, AK and Lencz,
T},
Title = {Multi-Trait Analysis of GWAS and Biological Insights Into
Cognition: A Response to Hill (2018).},
Journal = {Twin Res Hum Genet},
Volume = {21},
Number = {5},
Pages = {394-397},
Year = {2018},
Month = {October},
Abstract = {Hill (Twin Research and Human Genetics, Vol. 21, 2018,
84-88) presented a critique of our recently published paper
in Cell Reports entitled 'Large-Scale Cognitive GWAS
Meta-Analysis Reveals Tissue-Specific Neural Expression and
Potential Nootropic Drug Targets' (Lam et al., Cell Reports,
Vol. 21, 2017, 2597-2613). Specifically, Hill offered
several interrelated comments suggesting potential problems
with our use of a new analytic method called Multi-Trait
Analysis of GWAS (MTAG) (Turley et al., Nature Genetics,
Vol. 50, 2018, 229-237). In this brief article, we respond
to each of these concerns. Using empirical data, we conclude
that our MTAG results do not suffer from 'inflation in the
FDR [false discovery rate]', as suggested by Hill (Twin
Research and Human Genetics, Vol. 21, 2018, 84-88), and are
not 'more relevant to the genetic contributions to education
than they are to the genetic contributions to
intelligence'.},
Doi = {10.1017/thg.2018.46},
Key = {fds335682}
}
@article{fds335686,
Author = {d'Arbeloff, TC and Kim, MJ and Knodt, AR and Radtke, SR and Brigidi, BD and Hariri, AR},
Title = {Microstructural integrity of a pathway connecting the
prefrontal cortex and amygdala moderates the association
between cognitive reappraisal and negative
emotions.},
Journal = {Emotion (Washington, D.C.)},
Volume = {18},
Number = {6},
Pages = {912-915},
Year = {2018},
Month = {September},
Abstract = {Cognitive reappraisal is a commonly used form of emotion
regulation that utilizes frontal-executive control to
reframe an approaching emotional event to moderate its
potential psychological impact. Use of cognitive reappraisal
has been associated with diminished experience of anxiety
and depressive symptoms, as well as greater overall
well-being. Using data from a study of 647 healthy young
adults, we provide initial evidence that an association
between typical use of cognitive reappraisal in daily life
and the experience of anxiety and depressive symptoms is
moderated by the microstructural integrity of the uncinate
fasciculus, which provides a major anatomical link between
the amygdala and prefrontal cortex. Our findings are
consistent with the nature of top-down regulation of
bottom-up negative emotions and suggest the uncinate
fasciculus may be a useful target in the search for
biomarkers predicting not only disorder risk but also
response to psychotherapy utilizing cognitive reappraisal.
(PsycINFO Database Record},
Doi = {10.1037/emo0000447},
Key = {fds335686}
}
@article{fds332980,
Author = {Hanson, JL and Knodt, AR and Brigidi, BD and Hariri,
AR},
Title = {Heightened connectivity between the ventral striatum and
medial prefrontal cortex as a biomarker for stress-related
psychopathology: understanding interactive effects of early
and more recent stress.},
Journal = {Psychological medicine},
Volume = {48},
Number = {11},
Pages = {1835-1843},
Year = {2018},
Month = {August},
Abstract = {<h4>Background</h4>The experience of childhood maltreatment
is a significant risk factor for the development of
depression. This risk is particularly heightened after
exposure to additional, more contemporaneous stress. While
behavioral evidence exists for this relation, little is
known about biological correlates of these stress
interactions. Identifying such correlates may provide
biomarkers of risk for later depression.<h4>Methods</h4>Here,
we leverage behavioral, experiential, and neuroimaging data
from the Duke Neurogenetics Study to identify potential
biomarkers of stress exposure. Based on the past research,
we were specifically interested in reward-related
connectivity and the interaction of early and more recent
stress. We examined psychophysiological interactions between
the ventral striatum and other brain regions in relation to
these stress variables, as well as measures of internalizing
symptomatology (n = 926, participant age range = 18-22 years
of age).<h4>Results</h4>We found relatively increased
reward-related functional connectivity between the left
ventral striatum and the medial prefrontal cortex in
individuals exposed to greater levels of childhood
maltreatment who also experienced greater levels of recent
life stress (β = 0.199, p < 0.005). This pattern of
functional connectivity was further associated with elevated
symptoms of depression (β = 0.089, p = 0.006). Furthermore,
using a moderated mediation framework, we demonstrate that
this functional connectivity provides a biological link
between cumulative stress exposure and internalizing
symptomatology.<h4>Conclusions</h4>These findings suggest a
novel biomarker linking cumulative stress exposure with the
later experience of depressive symptoms. Our results are
discussed in the context of past research examining stress
exposure in relation to depression.},
Doi = {10.1017/s0033291717003348},
Key = {fds332980}
}
@article{fds364155,
Author = {Elsayed, NM and Kim, MJ and Fields, KM and Olvera, RL and Hariri, AR and Williamson, DE},
Title = {Trajectories of Alcohol Initiation and Use During
Adolescence: The Role of Stress and Amygdala
Reactivity.},
Journal = {Journal of the American Academy of Child and Adolescent
Psychiatry},
Volume = {57},
Number = {8},
Pages = {550-560},
Year = {2018},
Month = {August},
Abstract = {<h4>Objective</h4>Early alcohol use initiation predicts
onset of alcohol use disorders in adulthood. However, little
is known about developmental trajectories of alcohol use
initiation and their putative biological and environmental
correlates.<h4>Method</h4>Adolescents (N = 330) with high
or low familial loading for depression were assessed
annually for up to 6 years. Data were collected assessing
affective symptoms, alcohol use, and stress at each
assessment. Adolescents also participated in a functional
magnetic resonance imaging protocol that included
measurement of threat-related amygdala and reward-related
ventral striatum activity.<h4>Results</h4>Latent class
analyses identified 2 trajectories of alcohol use
initiation. Early initiators (n = 32) reported greater
baseline alcohol use and rate of change of use compared with
late initiators and/or current abstainers (n = 298). Early
initiators reported higher baseline levels of stressful life
events (p = .001) and exhibited higher amygdala (p = .001)
but not ventral striatum activity compared with late
initiators. Early initiators were 15.3 times more likely to
have a full drink (p < .0001), 9.1 times more likely to
experience intoxication (p < .0001), and 6.7 times more
likely to develop an alcohol use disorder by 19 years of age
compared with late initiators (p = .003).<h4>Conclusion</h4>Adolescents
on a trajectory of early alcohol use initiation have higher
levels of stress, have increased threat-related amygdala
activity, are more likely to consume a full standard
alcoholic drink, are more likely to experience early
intoxication, and are at a heightened risk for the onset of
an alcohol use disorder.},
Doi = {10.1016/j.jaac.2018.05.011},
Key = {fds364155}
}
@article{fds335683,
Author = {Kim, MJ and Scult, MA and Knodt, AR and Radtke, SR and d'Arbeloff, TC and Brigidi, BD and Hariri, AR},
Title = {A Link Between Childhood Adversity and Trait Anger Reflects
Relative Activity of the Amygdala and Dorsolateral
Prefrontal Cortex.},
Journal = {Biological psychiatry. Cognitive neuroscience and
neuroimaging},
Volume = {3},
Number = {7},
Pages = {644-649},
Year = {2018},
Month = {July},
Abstract = {<h4>Background</h4>Trait anger, or the dispositional
tendency to experience a wide range of situations as
annoying or frustrating, is associated with negative mental
and physical health outcomes. The experience of adversity
during childhood is one risk factor for the later emergence
of high trait anger. This association has been hypothesized
to reflect alterations in neural circuits supporting
bottom-up threat processing and top-down executive
control.<h4>Methods</h4>Here, using functional magnetic
resonance imaging and self-report questionnaire data from
220 volunteers, we examined how individual differences in
top-down prefrontal executive control and bottom-up amygdala
threat activity modulate the association between childhood
adversity and trait anger during young adulthood.<h4>Results</h4>We
report that the association between childhood adversity and
trait anger is attenuated specifically in young adults who
have both relatively low threat-related amygdala activity
and high executive control-related dorsolateral prefrontal
cortex activity.<h4>Conclusions</h4>These brain activity
patterns suggest that simultaneous consideration of their
underlying cognitive processes-namely, threat processing and
executive control-may be useful in strategies designed to
mitigate the negative mental health consequences of
childhood adversity.},
Doi = {10.1016/j.bpsc.2018.03.006},
Key = {fds335683}
}
@article{fds335684,
Author = {Savage, JE and Jansen, PR and Stringer, S and Watanabe, K and Bryois, J and de Leeuw, CA and Nagel, M and Awasthi, S and Barr, PB and Coleman, JRI and Grasby, KL and Hammerschlag, AR and Kaminski, JA and Karlsson, R and Krapohl, E and Lam, M and Nygaard, M and Reynolds, CA and Trampush, JW and Young, H and Zabaneh, D and Hägg, S and Hansell, NK and Karlsson, IK and Linnarsson, S and Montgomery, GW and Muñoz-Manchado, AB and Quinlan,
EB and Schumann, G and Skene, NG and Webb, BT and White, T and Arking, DE and Avramopoulos, D and Bilder, RM and Bitsios, P and Burdick, KE and Cannon, TD and Chiba-Falek, O and Christoforou, A and Cirulli, ET and Congdon, E and Corvin, A and Davies, G and Deary, IJ and DeRosse, P and Dickinson, D and Djurovic, S and Donohoe, G and Conley, ED and Eriksson,
JG and Espeseth, T and Freimer, NA and Giakoumaki, S and Giegling, I and Gill, M and Glahn, DC and Hariri, AR and Hatzimanolis, A and Keller, MC and Knowles, E and Koltai, D and Konte, B and Lahti, J and Le Hellard and S and Lencz, T and Liewald, DC and London, E and Lundervold, AJ and Malhotra,
AK and Melle, I and Morris, D and Need, AC and Ollier, W and Palotie, A and Payton, A and Pendleton, N and Poldrack, RA and Räikkönen, K and Reinvang, I and Roussos, P and Rujescu, D and Sabb, FW and Scult, MA and Smeland, OB and Smyrnis, N and Starr, JM and Steen, VM and Stefanis, NC and Straub, RE and Sundet, K and Tiemeier, H and Voineskos, AN and Weinberger, DR and Widen, E and Yu, J and Abecasis, G and Andreassen,
OA and Breen, G and Christiansen, L and Debrabant, B and Dick, DM and Heinz, A and Hjerling-Leffler, J and Ikram, MA and Kendler, KS and Martin, NG and Medland, SE and Pedersen, NL and Plomin, R and Polderman,
TJC and Ripke, S and van der Sluis, S and Sullivan, PF and Vrieze, SI and Wright, MJ and Posthuma, D},
Title = {Genome-wide association meta-analysis in 269,867 individuals
identifies new genetic and functional links to
intelligence.},
Journal = {Nat Genet},
Volume = {50},
Number = {7},
Pages = {912-919},
Year = {2018},
Month = {July},
Abstract = {Intelligence is highly heritable1 and a major determinant of
human health and well-being2. Recent genome-wide
meta-analyses have identified 24 genomic loci linked to
variation in intelligence3-7, but much about its genetic
underpinnings remains to be discovered. Here, we present a
large-scale genetic association study of intelligence
(n = 269,867), identifying 205 associated genomic loci
(190 new) and 1,016 genes (939 new) via positional mapping,
expression quantitative trait locus (eQTL) mapping,
chromatin interaction mapping, and gene-based association
analysis. We find enrichment of genetic effects in conserved
and coding regions and associations with 146 nonsynonymous
exonic variants. Associated genes are strongly expressed in
the brain, specifically in striatal medium spiny neurons and
hippocampal pyramidal neurons. Gene set analyses implicate
pathways related to nervous system development and synaptic
structure. We confirm previous strong genetic correlations
with multiple health-related outcomes, and Mendelian
randomization analysis results suggest protective effects of
intelligence for Alzheimer's disease and ADHD and
bidirectional causation with pleiotropic effects for
schizophrenia. These results are a major step forward in
understanding the neurobiology of cognitive function as well
as genetically related neurological and psychiatric
disorders.},
Doi = {10.1038/s41588-018-0152-6},
Key = {fds335684}
}
@article{fds331566,
Author = {Avinun, R and Nevo, A and Knodt, AR and Elliott, ML and Hariri,
AR},
Title = {Replication in Imaging Genetics: The Case of Threat-Related
Amygdala Reactivity.},
Journal = {Biological psychiatry},
Volume = {84},
Number = {2},
Pages = {148-159},
Year = {2018},
Month = {July},
Abstract = {<h4>Background</h4>Low replication rates are a concern in
most, if not all, scientific disciplines. In psychiatric
genetics specifically, targeting intermediate brain
phenotypes, which are more closely associated with putative
genetic effects, was touted as a strategy leading to
increased power and replicability. In the current study, we
attempted to replicate previously published associations
between single nucleotide polymorphisms and threat-related
amygdala reactivity, which represents a robust brain
phenotype not only implicated in the pathophysiology of
multiple disorders, but also used as a biomarker of future
risk.<h4>Methods</h4>We conducted a literature search for
published associations between single nucleotide
polymorphisms and threat-related amygdala reactivity and
found 37 unique findings. Our replication sample consisted
of 1117 young adult volunteers (629 women, mean age 19.72 ±
1.25 years) for whom both genetic and functional magnetic
resonance imaging data were available.<h4>Results</h4>Of the
37 unique associations identified, only three replicated as
previously reported. When exploratory analyses were
conducted with different model parameters compared to the
original findings, significant associations were identified
for 28 additional studies: eight of these were for a
different contrast/laterality; five for a different gender
and/or race/ethnicity; and 15 in the opposite direction and
for a different contrast, laterality, gender, and/or
race/ethnicity. No significant associations, regardless of
model parameters, were detected for six studies. Notably,
none of the significant associations survived correction for
multiple comparisons.<h4>Conclusions</h4>We discuss these
patterns of poor replication with regard to the general
strategy of targeting intermediate brain phenotypes in
genetic association studies and the growing importance of
advancing the replicability of imaging genetics
findings.},
Doi = {10.1016/j.biopsych.2017.11.010},
Key = {fds331566}
}
@article{fds335691,
Author = {Miller, JA and Scult, MA and Conley, ED and Chen, Q and Weinberger, DR and Hariri, AR},
Title = {Effects of Schizophrenia Polygenic Risk Scores on Brain
Activity and Performance During Working Memory Subprocesses
in Healthy Young Adults.},
Journal = {Schizophrenia bulletin},
Volume = {44},
Number = {4},
Pages = {844-853},
Year = {2018},
Month = {June},
Abstract = {Recent work has begun to shed light on the neural correlates
and possible mechanisms of polygenic risk for schizophrenia.
Here, we map a schizophrenia polygenic risk profile score
(PRS) based on genome-wide association study significant
loci onto variability in the activity and functional
connectivity of a frontoparietal network supporting the
manipulation versus maintenance of information during a
numerical working memory (WM) task in healthy young adults
(n = 99, mean age = 19.8). Our analyses revealed that higher
PRS was associated with hypoactivity of the dorsolateral
prefrontal cortex (dlPFC) during the manipulation but not
maintenance of information in WM (r2 = .0576, P = .018).
Post hoc analyses revealed that PRS-modulated dlPFC
hypoactivity correlated with faster reaction times during WM
manipulation (r2 = .0967, P = .002), and faster processing
speed (r2 = .0967, P = .003) on a separate behavioral task.
These PRS-associated patterns recapitulate dlPFC
hypoactivity observed in patients with schizophrenia during
central executive manipulation of information in WM on this
task.},
Doi = {10.1093/schbul/sbx140},
Key = {fds335691}
}
@article{fds335685,
Author = {Davies, G and Lam, M and Harris, SE and Trampush, JW and Luciano, M and Hill, WD and Hagenaars, SP and Ritchie, SJ and Marioni, RE and Fawns-Ritchie, C and Liewald, DCM and Okely, JA and Ahola-Olli, AV and Barnes, CLK and Bertram, L and Bis, JC and Burdick, KE and Christoforou,
A and DeRosse, P and Djurovic, S and Espeseth, T and Giakoumaki, S and Giddaluru, S and Gustavson, DE and Hayward, C and Hofer, E and Ikram,
MA and Karlsson, R and Knowles, E and Lahti, J and Leber, M and Li, S and Mather, KA and Melle, I and Morris, D and Oldmeadow, C and Palviainen,
T and Payton, A and Pazoki, R and Petrovic, K and Reynolds, CA and Sargurupremraj, M and Scholz, M and Smith, JA and Smith, AV and Terzikhan, N and Thalamuthu, A and Trompet, S and van der Lee, SJ and Ware, EB and Windham, BG and Wright, MJ and Yang, J and Yu, J and Ames, D and Amin, N and Amouyel, P and Andreassen, OA and Armstrong, NJ and Assareh,
AA and Attia, JR and Attix, D and Avramopoulos, D and Bennett, DA and Böhmer, AC and Boyle, PA and Brodaty, H and Campbell, H and Cannon, TD and Cirulli, ET and Congdon, E and Conley, ED and Corley, J and Cox, SR and Dale, AM and Dehghan, A and Dick, D and Dickinson, D and Eriksson, JG and Evangelou, E and Faul, JD and Ford, I and Freimer, NA and Gao, H and Giegling, I and Gillespie, NA and Gordon, SD and Gottesman, RF and Griswold, ME and Gudnason, V and Harris, TB and Hartmann, AM and Hatzimanolis, A and Heiss, G and Holliday, EG and Joshi, PK and Kähönen, M and Kardia, SLR and Karlsson, I and Kleineidam, L and Knopman, DS and Kochan, NA and Konte, B and Kwok, JB and Le Hellard and S and Lee, T and Lehtimäki, T and Li, S-C and Lill, CM and Liu, T and Koini, M and London, E and Longstreth, WT and Lopez, OL and Loukola, A and Luck, T and Lundervold, AJ and Lundquist, A and Lyytikäinen, L-P and Martin, NG and Montgomery, GW and Murray, AD and Need, AC and Noordam, R and Nyberg, L and Ollier, W and Papenberg, G and Pattie, A and Polasek, O and Poldrack,
RA and Psaty, BM and Reppermund, S and Riedel-Heller, SG and Rose, RJ and Rotter, JI and Roussos, P and Rovio, SP and Saba, Y and Sabb, FW and Sachdev, PS and Satizabal, CL and Schmid, M and Scott, RJ and Scult, MA and Simino, J and Slagboom, PE and Smyrnis, N and Soumaré, A and Stefanis,
NC and Stott, DJ and Straub, RE and Sundet, K and Taylor, AM and Taylor,
KD and Tzoulaki, I and Tzourio, C and Uitterlinden, A and Vitart, V and Voineskos, AN and Kaprio, J and Wagner, M and Wagner, H and Weinhold, L and Wen, KH and Widen, E and Yang, Q and Zhao, W and Adams, HHH and Arking, DE and Bilder, RM and Bitsios, P and Boerwinkle, E and Chiba-Falek, O and Corvin, A and De Jager and PL and Debette, S and Donohoe, G and Elliott, P and Fitzpatrick, AL and Gill, M and Glahn, DC and Hägg, S and Hansell, NK and Hariri, AR and Ikram, MK and Jukema, JW and Vuoksimaa, E and Keller, MC and Kremen, WS and Launer, L and Lindenberger, U and Palotie, A and Pedersen, NL and Pendleton, N and Porteous, DJ and Räikkönen, K and Raitakari, OT and Ramirez, A and Reinvang, I and Rudan, I and Dan
Rujescu, and Schmidt, R and Schmidt, H and Schofield, PW and Schofield,
PR and Starr, JM and Steen, VM and Trollor, JN and Turner, ST and Van
Duijn, CM and Villringer, A and Weinberger, DR and Weir, DR and Wilson,
JF and Malhotra, A and McIntosh, AM and Gale, CR and Seshadri, S and Mosley, TH and Bressler, J and Lencz, T and Deary,
IJ},
Title = {Study of 300,486 individuals identifies 148 independent
genetic loci influencing general cognitive
function.},
Journal = {Nat Commun},
Volume = {9},
Number = {1},
Pages = {2098},
Year = {2018},
Month = {May},
Abstract = {General cognitive function is a prominent and relatively
stable human trait that is associated with many important
life outcomes. We combine cognitive and genetic data from
the CHARGE and COGENT consortia, and UK Biobank (total
N = 300,486; age 16-102) and find 148 genome-wide
significant independent loci (P < 5 × 10-8)
associated with general cognitive function. Within the novel
genetic loci are variants associated with neurodegenerative
and neurodevelopmental disorders, physical and psychiatric
illnesses, and brain structure. Gene-based analyses find 709
genes associated with general cognitive function. Expression
levels across the cortex are associated with general
cognitive function. Using polygenic scores, up to 4.3% of
variance in general cognitive function is predicted in
independent samples. We detect significant genetic overlap
between general cognitive function, reaction time, and many
health variables including eyesight, hypertension, and
longevity. In conclusion we identify novel genetic loci and
pathways contributing to the heritability of general
cognitive function.},
Doi = {10.1038/s41467-018-04362-x},
Key = {fds335685}
}
@article{fds335687,
Author = {Agrawal, A and Chou, Y-L and Carey, CE and Baranger, DAA and Zhang, B and Sherva, R and Wetherill, L and Kapoor, M and Wang, J-C and Bertelsen, S and Anokhin, AP and Hesselbrock, V and Kramer, J and Lynskey, MT and Meyers,
JL and Nurnberger, JI and Rice, JP and Tischfield, J and Bierut, LJ and Degenhardt, L and Farrer, LA and Gelernter, J and Hariri, AR and Heath,
AC and Kranzler, HR and Madden, PAF and Martin, NG and Montgomery, GW and Porjesz, B and Wang, T and Whitfield, JB and Edenberg, HJ and Foroud, T and Goate, AM and Bogdan, R and Nelson, EC},
Title = {Genome-wide association study identifies a novel locus for
cannabis dependence.},
Journal = {Molecular psychiatry},
Volume = {23},
Number = {5},
Pages = {1293-1302},
Year = {2018},
Month = {May},
Abstract = {Despite moderate heritability, only one study has identified
genome-wide significant loci for cannabis-related
phenotypes. We conducted meta-analyses of genome-wide
association study data on 2080 cannabis-dependent cases and
6435 cannabis-exposed controls of European descent. A
cluster of correlated single-nucleotide polymorphisms (SNPs)
in a novel region on chromosome 10 was genome-wide
significant (lowest P=1.3E-8). Among the SNPs, rs1409568
showed enrichment for H3K4me1 and H3K427ac marks, suggesting
its role as an enhancer in addiction-relevant brain regions,
such as the dorsolateral prefrontal cortex and the angular
and cingulate gyri. This SNP is also predicted to modify
binding scores for several transcription factors. We found
modest evidence for replication for rs1409568 in an
independent cohort of African American (896 cases and 1591
controls; P=0.03) but not European American (EA; 781 cases
and 1905 controls) participants. The combined meta-analysis
(3757 cases and 9931 controls) indicated trend-level
significance for rs1409568 (P=2.85E-7). No genome-wide
significant loci emerged for cannabis dependence criterion
count (n=8050). There was also evidence that the minor
allele of rs1409568 was associated with a 2.1% increase in
right hippocampal volume in an independent sample of 430 EA
college students (fwe-P=0.008). The identification and
characterization of genome-wide significant loci for
cannabis dependence is among the first steps toward
understanding the biological contributions to the etiology
of this psychiatric disorder, which appears to be rising in
some developed nations.},
Doi = {10.1038/mp.2017.200},
Key = {fds335687}
}
@article{fds335690,
Author = {Elliott, ML and Romer, A and Knodt, AR and Hariri,
AR},
Title = {A Connectome Wide Functional Signature of Transdiagnostic
Risk for Mental Illness},
Journal = {Biological Psychiatry},
Volume = {84},
Number = {6},
Pages = {452-459},
Year = {2018},
Month = {April},
Abstract = {Background High rates of comorbidity, shared risk, and
overlapping therapeutic mechanisms have led psychopathology
research towards transdiagnostic dimensional investigations
of clustered symptoms. One influential framework accounts
for these transdiagnostic phenomena through a single general
factor, sometimes referred to as the ‘p’ factor,
associated with risk for all common forms of mental illness.
Methods Here we build on past research identifying unique
structural neural correlates of the p factor by conducting a
data-driven analysis of connectome wide intrinsic functional
connectivity (n = 605). Results We demonstrate that higher p
factor scores and associated risk for common mental illness
maps onto hyper-connectivity between visual association
cortex and both frontoparietal and default mode networks.
Conclusions These results provide initial evidence that the
transdiagnostic risk for common forms of mental illness is
associated with patterns of inefficient connectome wide
intrinsic connectivity between visual association cortex and
networks supporting executive control and self-referential
processes, networks which are often impaired across
categorical disorders.},
Doi = {10.1016/j.biopsych.2018.03.012},
Key = {fds335690}
}
@article{fds335688,
Author = {Chen, Q and Ursini, G and Romer, AL and Knodt, AR and Mezeivtch, K and Xiao, E and Pergola, G and Blasi, G and Straub, RE and Callicott, JH and Berman, KF and Hariri, AR and Bertolino, A and Mattay, VS and Weinberger, DR},
Title = {Schizophrenia polygenic risk score predicts mnemonic
hippocampal activity.},
Journal = {Brain : a journal of neurology},
Volume = {141},
Number = {4},
Pages = {1218-1228},
Year = {2018},
Month = {April},
Abstract = {The use of polygenic risk scores has become a practical
translational approach to investigating the complex genetic
architecture of schizophrenia, but the link between
polygenic risk scores and pathophysiological components of
this disorder has been the subject of limited research. We
investigated in healthy volunteers whether schizophrenia
polygenic risk score predicts hippocampal activity during
simple memory encoding, which has been proposed as a
risk-associated intermediate phenotype of schizophrenia. We
analysed the relationship between polygenic risk scores and
hippocampal activity in a discovery sample of 191 unrelated
healthy volunteers from the USA and in two independent
replication samples of 76 and 137 healthy unrelated
participants from Europe and the USA, respectively.
Polygenic risk scores for each individual were calculated as
the sum of the imputation probability of reference alleles
weighted by the natural log of odds ratio from the recent
schizophrenia genome-wide association study. We examined
hippocampal activity during simple memory encoding of novel
visual stimuli assessed using blood oxygen level-dependent
functional MRI. Polygenic risk scores were significantly
associated with hippocampal activity in the discovery sample
[P = 0.016, family-wise error (FWE) corrected within
Anatomical Automatic Labeling (AAL) bilateral
hippocampal-parahippocampal mask] and in both replication
samples (P = 0.033, FWE corrected within AAL right posterior
hippocampal-parahippocampal mask in Bari sample, and P =
0.002 uncorrected in the Duke Neurogenetics Study sample).
The relationship between polygenic risk scores and
hippocampal activity was consistently negative, i.e. lower
hippocampal activity in individuals with higher polygenic
risk scores, consistent with previous studies reporting
decreased hippocampal-parahippocampal activity during
declarative memory tasks in patients with schizophrenia and
in their healthy siblings. Polygenic risk scores accounted
for more than 8% of variance in hippocampal activity during
memory encoding in discovery sample. We conclude that
polygenic risk scores derived from the most recent
schizophrenia genome-wide association study predict
significant variability in hippocampal activity during
memory encoding in healthy participants. Our findings
validate mnemonic hippocampal activity as a genetic risk
associated intermediate phenotype of schizophrenia,
indicating that the aggregate neurobiological effect of
schizophrenia risk alleles converges on this pattern of
neural activity.awy004media15749593779001.},
Doi = {10.1093/brain/awy004},
Key = {fds335688}
}
@article{fds326208,
Author = {Romer, AL and Knodt, AR and Houts, R and Brigidi, BD and Moffitt, TE and Caspi, A and Hariri, AR},
Title = {Structural alterations within cerebellar circuitry are
associated with general liability for common mental
disorders.},
Journal = {Molecular psychiatry},
Volume = {23},
Number = {4},
Pages = {1084-1090},
Year = {2018},
Month = {April},
Abstract = {Accumulating mental-health research encourages a shift in
focus toward transdiagnostic dimensional features that are
shared across categorical disorders. In support of this
shift, recent studies have identified a general liability
factor for psychopathology-sometimes called the 'p factor'-
that underlies shared risk for a wide range of mental
disorders. Identifying neural correlates of this general
liability would substantiate its importance in
characterizing the shared origins of mental disorders and
help us begin to understand the mechanisms through which the
'p factor' contributes to risk. Here we believe we first
replicate the 'p factor' using cross-sectional data from a
volunteer sample of 1246 university students, and then using
high-resolution multimodal structural neuroimaging, we
demonstrate that individuals with higher 'p factor' scores
show reduced structural integrity of white matter pathways,
as indexed by lower fractional anisotropy values, uniquely
within the pons. Whole-brain analyses further revealed that
higher 'p factor' scores are associated with reduced gray
matter volume in the occipital lobe and left cerebellar
lobule VIIb, which is functionally connected with prefrontal
regions supporting cognitive control. Consistent with the
preponderance of cerebellar afferents within the pons, we
observed a significant positive correlation between the
white matter integrity of the pons and cerebellar gray
matter volume associated with higher 'p factor' scores. The
results of our analyses provide initial evidence that
structural alterations in corticocerebellar circuitry
supporting core functions related to the basic integration,
coordination and monitoring of information may contribute to
a general liability for common mental disorders.},
Doi = {10.1038/mp.2017.57},
Key = {fds326208}
}
@article{fds332044,
Author = {Scult, MA and Hariri, AR},
Title = {A BRIEF INTRODUCTION TO THE NEUROGENETICS OF
COGNITION-EMOTION INTERACTIONS.},
Journal = {Current opinion in behavioral sciences},
Volume = {19},
Pages = {50-54},
Year = {2018},
Month = {February},
Abstract = {Neuroscience research has demonstrated that cognition,
emotion, and their dynamic interactions emerge from complex
and flexible patterns of activity across distributed neural
circuits. A parallel branch of research in genetics has
begun to identify common variation in the human DNA sequence
(i.e., genome) that may shape individual differences in
cognition-emotion interactions by altering molecular and
cellular pathways that modulate the activity of these neural
circuits. Here we provide a brief introduction to such
neurogenetics research and how it may usefully inform our
understanding of the biological mechanisms through which
dynamic cognition-emotion interactions emerge and,
subsequently, help shape normal and abnormal
behavior.},
Doi = {10.1016/j.cobeha.2017.09.014},
Key = {fds332044}
}
@article{fds331564,
Author = {Swartz, JR and Knodt, AR and Radtke, SR and Hariri,
AR},
Title = {Post-secondary maternal education buffers against neural
risk for psychological vulnerability to future life
stress.},
Journal = {Neuropsychologia},
Volume = {109},
Pages = {134-139},
Publisher = {Elsevier BV},
Year = {2018},
Month = {January},
Abstract = {We have previously reported that threat-related amygdala
activity measured during a baseline fMRI scan predicts the
experience of depression and anxiety associated with
stressful life events years later. Here, we examine whether
two broad measures of childhood environmental enrichment,
namely parental educational achievement and subjective
parental socioeconomic status, buffer against the effects of
amygdala activity on future vulnerability to stress.
Analyses of data available from 579 young adults revealed
that maternal, but not paternal, educational achievement
moderates the association between amygdala activity, recent
life stress, and changes in mood and anxiety symptoms, even
when controlling for participants' current subjective
socioeconomic status. Specifically, only participants
reporting lower maternal educational achievement exhibited
our previously observed interaction between amygdala
activity and future life stress predicting increases in
depression and anxiety. These results suggest that higher
maternal educational achievement may help buffer stress
sensitivity associated with heightened threat-related
amygdala activity.},
Doi = {10.1016/j.neuropsychologia.2017.12.019},
Key = {fds331564}
}
@article{fds332756,
Author = {Nikolova, YS and Misquitta, KA and Rocco, BR and Prevot, TD and Knodt,
AR and Ellegood, J and Voineskos, AN and Lerch, JP and Hariri, AR and Sibille, E and Banasr, M},
Title = {Shifting priorities: highly conserved behavioral and brain
network adaptations to chronic stress across
species.},
Journal = {Translational psychiatry},
Volume = {8},
Number = {1},
Pages = {26},
Year = {2018},
Month = {January},
Abstract = {Parallel clinical and preclinical research have begun to
illuminate the biological basis of stress-related disorders,
including major depression, but translational bridges
informing discrete mechanistic targets for intervention are
missing. To address this critical need, we used structural
MRI in a mouse model and in a large human sample to examine
stress effects on brain structure that may be conserved
across species. Specifically, we focused on a previously
unexplored approach, whole-brain structural covariance, as
it reflects synchronized changes in neuroanatomy,
potentially due to mutual trophic influences or shared
plasticity across regions. Using the unpredictable chronic
mild stress (UCMS) paradigm in mouse we first demonstrate
that UCMS-induced elevated behavioral emotionality
correlates with increased size of the amygdala and other
corticolimbic regions. We further identify focal increases
in the amygdala's 'hubness' (degree and strength) set
against the background of a global stress-related loss of
network clustering and modularity. These macroscopic changes
are supported on the molecular level by increased
postsynaptic density-95 protein in the amygdala, consistent
with stress-induced plastic changes and synaptic
strengthening. Finally, we provide clinical evidence that
strikingly similar structural network reorganization
patterns exist in young adults reporting high childhood
trauma and increased mood symptoms. Collectively, we provide
initial translational evidence for a conserved
stress-related increase in amygdala-centered structural
synchrony, as measured by enhanced structural covariance,
which is paralleled by a decrease in global structural
synchrony. This putative trade-off reflected in increased
amygdala-centered plastic changes at the expense of global
structural dedifferentiation may represent a mechanistic
pathway for depression and related psychopathology.},
Doi = {10.1038/s41398-017-0083-5},
Key = {fds332756}
}
@article{fds364156,
Author = {d'Arbeloff, TC and Freedy, KR and Knodt, AR and Radtke, SR and Brigidi,
BD and Hariri, AR},
Title = {Emotion Regulation and the Experience of Future Negative
Mood: The Importance of Assessing Social
Support.},
Journal = {Frontiers in psychology},
Volume = {9},
Pages = {2287},
Year = {2018},
Month = {January},
Abstract = {Emotion regulation refers to the use of various strategies,
such as cognitive reappraisal and expressive suppression, to
help manage our negative experiences, emotions, and
thoughts. Although such emotion regulation often occurs
within broader social dynamics and interactions, little is
known about how social contexts interact with specific
regulation strategies to shape the experience of negative
emotions. Using data from 544 young adult university
students, we provide initial evidence that habitual use of
cognitive reappraisal is associated with lower future
experience of depression and anxiety primarily through
higher perceived social support (PSS). In contrast,
expressive suppression is associated with higher future
depression and anxiety primarily through lower PSS. These
patterns are consistent with the importance of interpersonal
influences on emotion regulation and suggest that assessment
of social support can help elucidate the mechanisms of
successfully regulating negative mood.},
Doi = {10.3389/fpsyg.2018.02287},
Key = {fds364156}
}
@article{fds329769,
Author = {Dotterer, HL and Waller, R and Neumann, CS and Shaw, DS and Forbes, EE and Hariri, AR and Hyde, LW},
Title = {Examining the Factor Structure of the Self-Report of
Psychopathy Short-Form Across Four Young Adult
Samples.},
Journal = {Assessment},
Volume = {24},
Number = {8},
Pages = {1062-1079},
Year = {2017},
Month = {December},
Abstract = {Psychopathy refers to a range of complex behaviors and
personality traits, including callousness and antisocial
behavior, typically studied in criminal populations. Recent
studies have used self-reports to examine psychopathic
traits among noncriminal samples. The goal of the current
study was to examine the underlying factor structure of the
Self-Report of Psychopathy Scale-Short Form (SRP-SF) across
complementary samples and examine the impact of gender on
factor structure. We examined the structure of the SRP-SF
among 2,554 young adults from three undergraduate samples
and a high-risk young adult sample. Using confirmatory
factor analysis, a four-correlated factor model and a
four-bifactor model showed good fit to the data. Evidence of
weak invariance was found for both models across gender.
These findings highlight that the SRP-SF is a useful measure
of low-level psychopathic traits in noncriminal samples,
although the underlying factor structure may not fully
translate across men and women.},
Doi = {10.1177/1073191116640355},
Key = {fds329769}
}
@article{fds330405,
Author = {Lam, M and Trampush, JW and Yu, J and Knowles, E and Davies, G and Liewald,
DC and Starr, JM and Djurovic, S and Melle, I and Sundet, K and Christoforou, A and Reinvang, I and DeRosse, P and Lundervold, AJ and Steen, VM and Espeseth, T and Räikkönen, K and Widen, E and Palotie,
A and Eriksson, JG and Giegling, I and Konte, B and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier, W and Chiba-Falek, O and Attix, DK and Need, AC and Cirulli, ET and Voineskos,
AN and Stefanis, NC and Avramopoulos, D and Hatzimanolis, A and Arking,
DE and Smyrnis, N and Bilder, RM and Freimer, NA and Cannon, TD and London,
E and Poldrack, RA and Sabb, FW and Congdon, E and Conley, ED and Scult,
MA and Dickinson, D and Straub, RE and Donohoe, G and Morris, D and Corvin,
A and Gill, M and Hariri, AR and Weinberger, DR and Pendleton, N and Bitsios, P and Rujescu, D and Lahti, J and Le Hellard and S and Keller, MC and Andreassen, OA and Deary, IJ and Glahn, DC and Malhotra, AK and Lencz,
T},
Title = {Large-Scale Cognitive GWAS Meta-Analysis Reveals
Tissue-Specific Neural Expression and Potential Nootropic
Drug Targets.},
Journal = {Cell Rep},
Volume = {21},
Number = {9},
Pages = {2597-2613},
Year = {2017},
Month = {November},
Abstract = {Here, we present a large (n = 107,207) genome-wide
association study (GWAS) of general cognitive ability ("g"),
further enhanced by combining results with a large-scale
GWAS of educational attainment. We identified 70 independent
genomic loci associated with general cognitive ability.
Results showed significant enrichment for genes causing
Mendelian disorders with an intellectual disability
phenotype. Competitive pathway analysis implicated the
biological processes of neurogenesis and synaptic
regulation, as well as the gene targets of two pharmacologic
agents: cinnarizine, a T-type calcium channel blocker, and
LY97241, a potassium channel inhibitor. Transcriptome-wide
and epigenome-wide analysis revealed that the implicated
loci were enriched for genes expressed across all brain
regions (most strongly in the cerebellum). Enrichment was
exclusive to genes expressed in neurons but not
oligodendrocytes or astrocytes. Finally, we report genetic
correlations between cognitive ability and disparate
phenotypes including psychiatric disorders, several
autoimmune disorders, longevity, and maternal age at first
birth.},
Doi = {10.1016/j.celrep.2017.11.028},
Key = {fds330405}
}
@article{fds343723,
Author = {Scult, MA and Knodt, AR and Radtke, SR and Brigidi, BD and Hariri,
AR},
Title = {Prefrontal Executive Control Rescues Risk for Anxiety
Associated with High Threat and Low Reward Brain
Function},
Journal = {Cerebral Cortex},
Volume = {29},
Number = {1},
Pages = {70-76},
Year = {2017},
Month = {November},
Abstract = {Compared with neural biomarkers of risk for mental illness,
little is known about biomarkers of resilience. We explore
if greater executive control-related prefrontal activity may
function as a resilience biomarker by “rescuing” risk
associated with higher threat-related amygdala and lower
reward-related ventral striatum activity. Functional MRI was
used to assay baseline threat-related amygdala,
reward-related ventral striatum, and executive
control-related prefrontal activity in 120 young adult
volunteers. Participants provided self-reported mood and
anxiety ratings at baseline and follow-up. A moderation
model revealed a significant three-way interaction wherein
higher amygdala and lower ventral striatum activity
predicted increases in anxiety in those with average or low
but not high prefrontal activity. This effect was specific
to anxiety, with the neural biomarkers explaining ~10% of
the variance in change over time, above and beyond baseline
symptoms, sex, age, IQ, presence or absence of DMS-IV
diagnosis, and both early and recent stress. Our findings
are consistent with the importance of top-down executive
control in adaptive regulation of negative emotions, and
highlight a unique combination of neural biomarkers that may
identify at-risk individuals for whom the adoption of
strategies to improve executive control of negative emotions
may prove particularly beneficial.},
Doi = {10.1093/cercor/bhx304},
Key = {fds343723}
}
@article{fds332981,
Author = {Lissek, T and Adams, M and Adelman, J and Ahissar, E and Akaaboune, M and Akil, H and al'Absi, M and Arain, F and Arango-Lasprilla, JC and Atasoy,
D and Avila, J and Badawi, A and Bading, H and Baig, AM and Baleriola, J and Belmonte, C and Bertocchi, I and Betz, H and Blakemore, C and Blanke, O and Boehm-Sturm, P and Bonhoeffer, T and Bonifazi, P and Brose, N and Campolongo, P and Celikel, T and Chang, CC and Chang, T-Y and Citri, A and Cline, HT and Cortes, JM and Cullen, K and Dean, K and Delgado-Garcia,
JM and Desroches, M and Disterhoft, JF and Dowling, JE and Draguhn, A and El-Khamisy, SF and El Manira and A and Enam, SA and Encinas, JM and Erramuzpe, A and Esteban, JA and Fariñas, I and Fischer, E and Fukunaga, I and Gabilondo, I and Ganten, D and Gidon, A and Gomez-Esteban, JC and Greengard, P and Grinevich, V and Gruart, A and Guillemin, R and Hariri, AR and Hassan, B and Häusser, M and Hayashi,
Y and Hussain, NK and Jabbar, AA and Jaber, M and Jahn, R and Janahi, EM and Kabbaj, M and Kettenmann, H and Kindt, M and Knafo, S and Köhr, G and Komai, S and Krugers, H and Kuhn, B and Ghazal, NL and Larkum, ME and London, M and Lutz, B and Matute, C and Martinez-Millan, L and Maroun,
M and McGaugh, J and Moustafa, AA and Nasim, A and Nave, K-A and Neher, E and Nikolich, K and Outeiro, T and Palmer, LM and Penagarikano, O and Perez-Otano, I and Pfaff, DW and Poucet, B and Rahman, A-U and Ramos-Cabrer, P and Rashidy-Pour, A and Roberts, RJ and Rodrigues, S and Sanes, JR and Schaefer, AT and Segal, M and Segev, I and Shafqat, S and Siddiqui, NA and Soreq, H and Soriano-García, E and Spanagel, R and Sprengel, R and Stuart, G and Südhof, TC and Tønnesen, J and Treviño,
M and Uthman, BM and Venter, JC and Verkhratsky, A and Weiss, C and Wiesel,
TN and Yaksi, E and Yizhar, O and Young, LJ and Young, P and Zawia, NH and Zugaza, JL and Hasan, MT},
Title = {Building Bridges through Science.},
Journal = {Neuron},
Volume = {96},
Number = {4},
Pages = {730-735},
Year = {2017},
Month = {November},
Abstract = {Science is ideally suited to connect people from different
cultures and thereby foster mutual understanding. To promote
international life science collaboration, we have launched
"The Science Bridge" initiative. Our current project focuses
on partnership between Western and Middle Eastern
neuroscience communities.},
Doi = {10.1016/j.neuron.2017.09.028},
Key = {fds332981}
}
@article{fds330404,
Author = {Schaefer, JD and Scult, MA and Caspi, A and Arseneault, L and Belsky,
DW and Hariri, AR and Harrington, H and Houts, R and Ramrakha, S and Poulton, R and Moffitt, TE},
Title = {Is low cognitive functioning a predictor or consequence of
major depressive disorder? A test in two longitudinal birth
cohorts.},
Journal = {Development and psychopathology},
Pages = {1-15},
Year = {2017},
Month = {November},
Abstract = {Cognitive impairment has been identified as an important
aspect of major depressive disorder (MDD). We tested two
theories regarding the association between MDD and cognitive
functioning using data from longitudinal cohort studies. One
theory, the cognitive reserve hypothesis, suggests that
higher cognitive ability in childhood decreases risk of
later MDD. The second, the scarring hypothesis, instead
suggests that MDD leads to persistent cognitive deficits
following disorder onset. We tested both theories in the
Dunedin Study, a population-representative cohort followed
from birth to midlife and assessed repeatedly for both
cognitive functioning and psychopathology. We also used data
from the Environmental Risk Longitudinal Twin Study to test
whether childhood cognitive functioning predicts future MDD
risk independent of family-wide and genetic risk using a
discordant twin design. Contrary to both hypotheses, we
found that childhood cognitive functioning did not predict
future risk of MDD, nor did study members with a past
history of MDD show evidence of greater cognitive decline
unless MDD was accompanied by other comorbid psychiatric
conditions. Our results thus suggest that low cognitive
functioning is related to comorbidity, but is neither an
antecedent nor an enduring consequence of MDD. Future
research may benefit from considering cognitive deficits
that occur during depressive episodes from a transdiagnostic
perspective.},
Doi = {10.1017/s095457941700164x},
Key = {fds330404}
}
@article{fds328846,
Author = {Gard, AM and Waller, R and Shaw, DS and Forbes, EE and Hariri, AR and Hyde,
LW},
Title = {The long reach of early adversity: Parenting, stress, and
neural pathways to antisocial behavior in
adulthood.},
Journal = {Biological psychiatry. Cognitive neuroscience and
neuroimaging},
Volume = {2},
Number = {7},
Pages = {582-590},
Publisher = {Elsevier BV},
Year = {2017},
Month = {October},
Abstract = {<h4>Background</h4>Early life adversities including harsh
parenting, maternal depression, neighborhood deprivation,
and low family economic resources are more prevalent in
low-income urban environments and are potent predictors of
psychopathology, including, for boys, antisocial behavior
(AB). However, little research has examined how these
stressful experiences alter later neural function. Moreover,
identifying genetic markers of greater susceptibility to
adversity is critical to understanding biopsychosocial
pathways from early adversity to later psychopathology.<h4>Methods</h4>Within
a sample of 310 low-income boys followed from age 1.5 to 20,
multimethod assessments of adversities were examined at age
2 and age 12. At age 20, amygdala reactivity to emotional
facial expressions was assessed using fMRI, and symptoms of
Antisocial Personality Disorder were assessed via structured
clinical interview. Genetic variability in cortisol
signaling (<i>CRHR1</i>) was examined as a moderator of
pathways to amygdala reactivity.<h4>Results</h4>Observed
parenting and neighborhood deprivation at age 2 each
uniquely predicted amygdala reactivity to emotional faces at
age 20 over and above other adversities measured at multiple
developmental periods. Harsher parenting and greater
neighborhood deprivation in toddlerhood predicted
clinically-significant symptoms of AB via less amygdala
reactivity to fearful facial expressions and this pathway
was moderated by genetic variation in <i>CRHR1</i>.<h4>Conclusions</h4>These
results elucidate a pathway linking early adversity to less
amygdala reactivity to social signals of interpersonal
distress 18 years later, which in turn increased risk for
serious AB. Moreover, these findings suggest a genetic
marker of youth more susceptible to adversity.},
Doi = {10.1016/j.bpsc.2017.06.005},
Key = {fds328846}
}
@article{fds329468,
Author = {Avinun, R and Nevo, A and Knodt, AR and Elliott, ML and Radtke, SR and Brigidi, BD and Hariri, AR},
Title = {Reward-Related Ventral Striatum Activity Buffers against the
Experience of Depressive Symptoms Associated with Sleep
Disturbances.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {37},
Number = {40},
Pages = {9724-9729},
Year = {2017},
Month = {October},
Abstract = {Sleep disturbances represent one risk factor for depression.
Reward-related brain function, particularly the activity of
the ventral striatum (VS), has been identified as a
potential buffer against stress-related depression. We were
therefore interested in testing whether reward-related VS
activity would moderate the effect of sleep disturbances on
depression in a large cohort of young adults. Data were
available from 1129 university students (mean age 19.71 ±
1.25 years; 637 women) who completed a reward-related
functional MRI task to assay VS activity and provided
self-reports of sleep using the Pittsburgh Sleep Quality
Index and symptoms of depression using a summation of the
General Distress/Depression and Anhedonic Depression
subscales of the Mood and Anxiety Symptoms
Questionnaire-short form. Analyses revealed that as VS
activity increased the association between sleep
disturbances and depressive symptoms decreased. The
interaction between sleep disturbances and VS activity was
robust to the inclusion of sex, age, race/ethnicity, past or
present clinical disorder, early and recent life stress, and
anxiety symptoms, as well as the interactions between VS
activity and early or recent life stress as covariates. We
provide initial evidence that high reward-related VS
activity may buffer against depressive symptoms associated
with poor sleep. Our analyses help advance an emerging
literature supporting the importance of individual
differences in reward-related brain function as a potential
biomarker of relative risk for depression.<b>SIGNIFICANCE
STATEMENT</b> Sleep disturbances are a common risk factor
for depression. An emerging literature suggests that
reward-related activity of the ventral striatum (VS), a
brain region critical for motivation and goal-directed
behavior, may buffer against the effect of negative
experiences on the development of depression. Using data
from a large sample of 1129 university students we
demonstrate that as reward-related VS activity increases,
the link between sleep disturbances and depression
decreases. This finding contributes to accumulating research
demonstrating that reward-related brain function may be a
useful biomarker of relative risk for depression in the
context of negative experiences.},
Doi = {10.1523/jneurosci.1734-17.2017},
Key = {fds329468}
}
@article{fds329035,
Author = {Kim, MJ and Avinun, R and Knodt, AR and Radtke, SR and Hariri,
AR},
Title = {Neurogenetic plasticity and sex influence the link between
corticolimbic structural connectivity and trait
anxiety.},
Journal = {Scientific reports},
Volume = {7},
Number = {1},
Pages = {10959},
Year = {2017},
Month = {September},
Abstract = {Corticolimbic pathways connecting the amygdala and ventral
prefrontal cortex (vPFC) are linked with trait anxiety, but
it remains unclear what potential genetic moderators
contribute to this association. We sought to address this by
examining the inter-individual variability in
neuroplasticity as modeled by a functional polymorphism
(rs6265) in the human gene for brain derived neurotrophic
factor (BDNF). Amygdala-vPFC pathway fractional anisotropy
(FA) from 669 diffusion magnetic resonance images was used
to examine associations with trait anxiety as a function of
rs6265 genotype. We first replicated the inverse correlation
between trait anxiety and amygdala-vPFC pathway FA in women.
Furthermore, we found a moderating influence of rs6265
genotype such that the association between trait anxiety and
right amygdala-vPFC pathway FA was strongest in women
carrying the Met allele, which is linked with decreased
activity-dependent neuroplasticity. Results indicate that
the microstructural integrity of pathways supporting
communication between the amygdala and vPFC help shape the
expression of trait anxiety in women, and that this
association is further modulated by genetically driven
variability in neuroplasticity.},
Doi = {10.1038/s41598-017-11497-2},
Key = {fds329035}
}
@article{fds331565,
Author = {Baranger, DAA and Margolis, S and Hariri, AR and Bogdan,
R},
Title = {An earlier time of scan is associated with greater
threat-related amygdala reactivity.},
Journal = {Social cognitive and affective neuroscience},
Volume = {12},
Number = {8},
Pages = {1272-1283},
Year = {2017},
Month = {August},
Abstract = {Time-dependent variability in mood and anxiety suggest that
related neural phenotypes, such as threat-related amygdala
reactivity, may also follow a diurnal pattern. Here, using
data from 1,043 young adult volunteers, we found that
threat-related amygdala reactivity was negatively coupled
with time of day, an effect which was stronger in the left
hemisphere (β = -0.1083, p-fdr = 0.0012). This
effect was moderated by subjective sleep quality
(β = -0.0715, p-fdr = 0.0387); participants who
reported average and poor sleep quality had relatively
increased left amygdala reactivity in the morning.
Bootstrapped simulations suggest that similar
cross-sectional samples with at least 300 participants would
be able to detect associations between amygdala reactivity
and time of scan. In control analyses, we found no
associations between time and V1 activation. Our results
provide initial evidence that threat-related amygdala
reactivity may vary diurnally, and that this effect is
potentiated among individuals with average to low sleep
quality. More broadly, our results suggest that considering
time of scan in study design or modeling time of scan in
analyses, as well as collecting additional measures of
circadian variation, may be useful for understanding
threat-related neural phenotypes and their associations with
behavior, such as fear conditioning, mood and anxiety
symptoms, and related phenotypes.},
Doi = {10.1093/scan/nsx057},
Key = {fds331565}
}
@article{fds325037,
Author = {Bogdan, R and Salmeron, BJ and Carey, CE and Agrawal, A and Calhoun, VD and Garavan, H and Hariri, AR and Heinz, A and Hill, MN and Holmes, A and Kalin, NH and Goldman, D},
Title = {Imaging Genetics and Genomics in Psychiatry: A Critical
Review of Progress and Potential.},
Journal = {Biological psychiatry},
Volume = {82},
Number = {3},
Pages = {165-175},
Year = {2017},
Month = {August},
Abstract = {Imaging genetics and genomics research has begun to provide
insight into the molecular and genetic architecture of
neural phenotypes and the neural mechanisms through which
genetic risk for psychopathology may emerge. As it
approaches its third decade, imaging genetics is confronted
by many challenges, including the proliferation of studies
using small sample sizes and diverse designs, limited
replication, problems with harmonization of neural
phenotypes for meta-analysis, unclear mechanisms, and
evidence that effect sizes may be more modest than
originally posited, with increasing evidence of
polygenicity. These concerns have encouraged the field to
grow in many new directions, including the development of
consortia and large-scale data collection projects and the
use of novel methods (e.g., polygenic approaches, machine
learning) that enhance the quality of imaging genetic
studies but also introduce new challenges. We critically
review progress in imaging genetics and offer suggestions
and highlight potential pitfalls of novel approaches.
Ultimately, the strength of imaging genetics and genomics
lies in their translational and integrative potential with
other research approaches (e.g., nonhuman animal models,
psychiatric genetics, pharmacologic challenge) to elucidate
brain-based pathways that give rise to the vast individual
differences in behavior as well as risk for
psychopathology.},
Doi = {10.1016/j.biopsych.2016.12.030},
Key = {fds325037}
}
@article{fds315805,
Author = {Scult, MA and Knodt, AR and Hanson, JL and Ryoo, M and Adcock, RA and Hariri, AR and Strauman, TJ},
Title = {Individual differences in regulatory focus predict neural
response to reward.},
Journal = {Soc Neurosci},
Volume = {12},
Number = {4},
Pages = {419-429},
Year = {2017},
Month = {August},
ISSN = {1747-0919},
Abstract = {Although goal pursuit is related to both functioning of the
brain's reward circuits and psychological factors, the
literatures surrounding these concepts have often been
separate. Here, we use the psychological construct of
regulatory focus to investigate individual differences in
neural response to reward. Regulatory focus theory proposes
two motivational orientations for personal goal pursuit: (1)
promotion, associated with sensitivity to potential gain,
and (2) prevention, associated with sensitivity to potential
loss. The monetary incentive delay task was used to
manipulate reward circuit function, along with instructional
framing corresponding to promotion and prevention in a
within-subject design. We observed that the more promotion
oriented an individual was, the lower their ventral striatum
response to gain cues. Follow-up analyses revealed that
greater promotion orientation was associated with decreased
ventral striatum response even to no-value cues, suggesting
that promotion orientation may be associated with relatively
hypoactive reward system function. The findings are also
likely to represent an interaction between the cognitive and
motivational characteristics of the promotion system with
the task demands. Prevention orientation did not correlate
with ventral striatum response to gain cues, supporting the
discriminant validity of regulatory focus theory. The
results highlight a dynamic association between individual
differences in self-regulation and reward system
function.},
Doi = {10.1080/17470919.2016.1178170},
Key = {fds315805}
}
@article{fds325971,
Author = {Di Iorio and CR and Carey, CE and Michalski, LJ and Corral-Frias, NS and Conley, ED and Hariri, AR and Bogdan, R},
Title = {Hypothalamic-pituitary-adrenal axis genetic variation and
early stress moderates amygdala function.},
Journal = {Psychoneuroendocrinology},
Volume = {80},
Pages = {170-178},
Year = {2017},
Month = {June},
Abstract = {Early life stress may precipitate psychopathology, at least
in part, by influencing amygdala function. Converging
evidence across species suggests that links between
childhood stress and amygdala function may be dependent upon
hypothalamic-pituitary-adrenal (HPA) axis function. Using
data from college-attending non-Hispanic European-Americans
(n=308) who completed the Duke Neurogenetics Study, we
examined whether early life stress (ELS) and HPA axis
genetic variation interact to predict threat-related
amygdala function as well as psychopathology symptoms. A
biologically-informed multilocus profile score (BIMPS)
captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1
rs110402; NR3C2 rs5522/rs4635799) previously associated with
its function (higher BIMPS are reflective of higher HPA axis
activity). BOLD fMRI data were acquired while participants
completed an emotional face matching task. ELS and
depression and anxiety symptoms were measured using the
childhood trauma questionnaire and the mood and anxiety
symptom questionnaire, respectively. The interaction between
HPA axis BIMPS and ELS was associated with right amygdala
reactivity to threat-related stimuli, after accounting for
multiple testing (empirical-p=0.016). Among individuals with
higher BIMPS (i.e., the upper 21.4%), ELS was positively
coupled with threat-related amygdala reactivity, which was
absent among those with average or low BIMPS. Further,
higher BIMPS were associated with greater self-reported
anxious arousal, though there was no evidence that amygdala
function mediated this relationship. Polygenic variation
linked to HPA axis function may moderate the effects of
early life stress on threat-related amygdala function and
confer risk for anxiety symptomatology. However, what, if
any, neural mechanisms may mediate the relationship between
HPA axis BIMPS and anxiety symptomatology remains
unclear.},
Doi = {10.1016/j.psyneuen.2017.03.016},
Key = {fds325971}
}
@article{fds325036,
Author = {Dotterer, HL and Hyde, LW and Swartz, JR and Hariri, AR and Williamson,
DE},
Title = {Amygdala reactivity predicts adolescent antisocial behavior
but not callous-unemotional traits.},
Journal = {Developmental cognitive neuroscience},
Volume = {24},
Pages = {84-92},
Year = {2017},
Month = {April},
Abstract = {Recent neuroimaging studies have suggested divergent
relationships between antisocial behavior (AB) and
callous-unemotional (CU) traits and amygdala reactivity to
fearful and angry facial expressions in adolescents.
However, little work has examined if these findings extend
to dimensional measures of behavior in ethnically diverse,
non-clinical samples, or if participant sex, ethnicity,
pubertal stage, and age moderate associations. We examined
links between amygdala reactivity and dimensions of AB and
CU traits in 220 Hispanic and non-Hispanic Caucasian
adolescents (age 11-15; 49.5% female; 38.2% Hispanic), half
of whom had a family history for depression and thus were at
relatively elevated risk for late starting, emotionally
dysregulated AB. We found that AB was significantly related
to increased right amygdala reactivity to angry facial
expressions independent of sex, ethnicity, pubertal stage,
age, and familial risk status for depression. CU traits were
not related to fear- or anger-related amygdala reactivity.
The present study further demonstrates that AB is related to
increased amygdala reactivity to interpersonal threat cues
in adolescents, and that this relationship generalizes
across sex, ethnicity, pubertal stage, age, and familial
risk status for depression.},
Doi = {10.1016/j.dcn.2017.02.008},
Key = {fds325036}
}
@article{fds325035,
Author = {Swartz, JR and Prather, AA and Hariri, AR},
Title = {Threat-related amygdala activity is associated with
peripheral CRP concentrations in men but not
women.},
Journal = {Psychoneuroendocrinology},
Volume = {78},
Pages = {93-96},
Year = {2017},
Month = {April},
Abstract = {Increased levels of peripheral inflammatory markers,
including C-Reactive Protein (CRP), are associated with
increased risk for depression, anxiety, and suicidality. The
brain mechanisms that may underlie the association between
peripheral inflammation and internalizing problems remain to
be determined. The present study examines associations
between peripheral CRP concentrations and threat-related
amygdala activity, a neural biomarker of depression and
anxiety risk, in a sample of 172 young adult undergraduate
students. Participants underwent functional MRI scanning
while performing an emotional face matching task to obtain a
measure of threat-related amygdala activity to angry and
fearful faces; CRP concentrations were assayed from dried
blood spots. Results indicated a significant interaction
between CRP and sex: in men, but not women, higher CRP was
associated with higher threat-related amygdala activity.
These results add to the literature finding associations
between systemic levels of inflammation and brain function
and suggest that threat-related amygdala activity may serve
as a potential pathway through which heightened chronic
inflammation may increase risk for mood and anxiety
problems.},
Doi = {10.1016/j.psyneuen.2017.01.024},
Key = {fds325035}
}
@article{fds323253,
Author = {Carey, CE and Knodt, AR and Conley, ED and Hariri, AR and Bogdan,
R},
Title = {Reward-related ventral striatum activity links polygenic
risk for attention-deficit/hyperactivity disorder to
problematic alcohol use in young adulthood.},
Journal = {Biological psychiatry. Cognitive neuroscience and
neuroimaging},
Volume = {2},
Number = {2},
Pages = {180-187},
Publisher = {Elsevier BV},
Year = {2017},
Month = {March},
Abstract = {<h4>Background</h4>Problematic alcohol use in adolescence
and adulthood is a common and often debilitating correlate
of childhood attention-deficit/hyperactivity disorder
(ADHD). Converging evidence suggests that ADHD and
problematic alcohol use share a common additive genetic
basis, which may be mechanistically related to
reward-related brain function. In the current study, we
examined whether polygenic risk for childhood ADHD is linked
to problematic alcohol use in young adulthood through
alterations in reward-related activity of the ventral
striatum, a neural hub supporting appetitive behaviors and
reinforcement learning.<h4>Methods</h4>Genomic,
neuroimaging, and self-report data were available for 404
non-Hispanic European-American participants who completed
the ongoing Duke Neurogenetics Study. Polygenic risk scores
for childhood ADHD were calculated based on a genome-wide
association study meta-analysis conducted by the Psychiatric
Genomics Consortium and tested for association with
reward-related ventral striatum activity, measured using a
number-guessing functional magnetic resonance imaging
paradigm, and self-reported problematic alcohol use. A
mediational model tested whether ventral striatum activity
indirectly links polygenic risk for ADHD to problematic
alcohol use.<h4>Results</h4>Despite having no main effect on
problematic alcohol use, polygenic risk for childhood ADHD
was indirectly associated with problematic alcohol use
through increased reward-related ventral striatum
activity.<h4>Conclusions</h4>Individual differences in
reward-related brain function may, at least in part,
mechanistically link polygenic risk for childhood ADHD to
problematic alcohol use.},
Doi = {10.1016/j.bpsc.2016.10.003},
Key = {fds323253}
}
@article{fds323689,
Author = {Trampush, JW and Yang, MLZ and Yu, J and Knowles, E and Davies, G and Liewald, DC and Starr, JM and Djurovic, S and Melle, I and Sundet, K and Christoforou, A and Reinvang, I and DeRosse, P and Lundervold, AJ and Steen, VM and Espeseth, T and Räikkönen, K and Widen, E and Palotie,
A and Eriksson, JG and Giegling, I and Konte, B and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier, W and Horan, M and Chiba-Falek, O and Attix, DK and Need, AC and Cirulli, ET and Voineskos,
AN and Stefanis, NC and Avramopoulos, D and Hatzimanolis, A and Arking,
DE and Smyrnis, N and Bilder, RM and Freimer, NA and Cannon, TD and London,
E and Poldrack, RA and Sabb, FW and Congdon, E and Conley, ED and Scult,
MA and Dickinson, D and Straub, RE and Donohoe, G and Morris, D and Corvin,
A and Gill, M and Hariri, AR and Weinberger, DR and Pendleton, N and Bitsios, P and Rujescu, D and Lahti, J and Le Hellard and S and Keller, MC and Andreassen, OA and Deary, IJ and Glahn, DC and Malhotra, AK and Lencz,
T},
Title = {GWAS meta-analysis reveals novel loci and genetic correlates
for general cognitive function: a report from the COGENT
consortium.},
Journal = {Mol Psychiatry},
Volume = {22},
Number = {3},
Pages = {336-345},
Year = {2017},
Month = {March},
Abstract = {The complex nature of human cognition has resulted in
cognitive genomics lagging behind many other fields in terms
of gene discovery using genome-wide association study (GWAS)
methods. In an attempt to overcome these barriers, the
current study utilized GWAS meta-analysis to examine the
association of common genetic variation (~8M
single-nucleotide polymorphisms (SNP) with minor allele
frequency ⩾1%) to general cognitive function in a sample
of 35 298 healthy individuals of European ancestry across
24 cohorts in the Cognitive Genomics Consortium (COGENT). In
addition, we utilized individual SNP lookups and polygenic
score analyses to identify genetic overlap with other
relevant neurobehavioral phenotypes. Our primary GWAS
meta-analysis identified two novel SNP loci (top SNPs:
rs76114856 in the CENPO gene on chromosome 2 and rs6669072
near LOC105378853 on chromosome 1) associated with cognitive
performance at the genome-wide significance level (P<5 ×
10-8). Gene-based analysis identified an additional three
Bonferroni-corrected significant loci at chromosomes
17q21.31, 17p13.1 and 1p13.3. Altogether, common variation
across the genome resulted in a conservatively estimated SNP
heritability of 21.5% (s.e.=0.01%) for general cognitive
function. Integration with prior GWAS of cognitive
performance and educational attainment yielded several
additional significant loci. Finally, we found robust
polygenic correlations between cognitive performance and
educational attainment, several psychiatric disorders, birth
length/weight and smoking behavior, as well as a novel
genetic association to the personality trait of openness.
These data provide new insight into the genetics of
neurocognitive function with relevance to understanding the
pathophysiology of neuropsychiatric illness.},
Doi = {10.1038/mp.2016.244},
Key = {fds323689}
}
@article{fds330406,
Author = {Swartz, JR and Waller, R and Bogdan, R and Knodt, AR and Sabhlok, A and Hyde, LW and Hariri, AR},
Title = {A Common Polymorphism in a Williams Syndrome Gene Predicts
Amygdala Reactivity and Extraversion in Healthy
Adults.},
Journal = {Biological psychiatry},
Volume = {81},
Number = {3},
Pages = {203-210},
Year = {2017},
Month = {February},
Abstract = {<h4>Background</h4>Williams syndrome (WS), a genetic
disorder resulting from hemizygous microdeletion of
chromosome 7q11.23, has emerged as a model for identifying
the genetic architecture of socioemotional behavior. Common
polymorphisms in GTF2I, which is found within the WS
microdeletion, have been associated with reduced social
anxiety in the general population. Identifying neural
phenotypes affected by these polymorphisms would help
advance our understanding not only of this specific genetic
association but also of the broader neurogenetic mechanisms
of variability in socioemotional behavior.<h4>Methods</h4>Through
an ongoing parent protocol, the Duke Neurogenetics Study, we
measured threat-related amygdala reactivity to fearful and
angry facial expressions using functional magnetic resonance
imaging, assessed trait personality using the Revised NEO
Personality Inventory, and imputed GTF2I rs13227433 from
saliva-derived DNA using custom Illumina arrays.
Participants included 808 non-Hispanic Caucasian, African
American, and Asian university students.<h4>Results</h4>The
GTF2I rs13227433 AA genotype, previously associated with
lower social anxiety, predicted decreased threat-related
amygdala reactivity. An indirect effect of GTF2I genotype on
the warmth facet of extraversion was mediated by decreased
threat-related amygdala reactivity in women but not
men.<h4>Conclusions</h4>A common polymorphism in the WS gene
GTF2I associated with reduced social anxiety predicts
decreased threat-related amygdala reactivity, which mediates
an association between genotype and increased warmth in
women. These results are consistent with reduced
threat-related amygdala reactivity in WS and suggest that
common variation in GTF2I contributes to broader variability
in socioemotional brain function and behavior, with
implications for understanding the neurogenetic bases of WS
as well as social anxiety.},
Doi = {10.1016/j.biopsych.2015.12.007},
Key = {fds330406}
}
@article{fds322497,
Author = {Swartz, JR and Knodt, AR and Radtke, SR and Hariri,
AR},
Title = {Peering into the brain to predict behavior: Peer-reported,
but not self-reported, conscientiousness links
threat-related amygdala activity to future problem
drinking.},
Journal = {NeuroImage},
Volume = {146},
Pages = {894-903},
Year = {2017},
Month = {February},
Abstract = {Personality traits such as conscientiousness as
self-reported by individuals can help predict a range of
outcomes, from job performance to longevity. Asking others
to rate the personality of their acquaintances often
provides even better predictive power than using
self-report. Here, we examine whether peer-reported
personality can provide a better link between brain
function, namely threat-related amygdala activity, and
future health-related behavior, namely problem drinking,
than self-reported personality. Using data from a sample of
377 young adult university students who were rated on five
personality traits by peers, we find that higher
threat-related amygdala activity to fearful facial
expressions is associated with higher peer-reported, but not
self-reported, conscientiousness. Moreover, higher
peer-reported, but not self-reported, conscientiousness
predicts lower future problem drinking more than one year
later, an effect specific to men. Remarkably, relatively
higher amygdala activity has an indirect effect on future
drinking behavior in men, linked by peer-reported
conscientiousness to lower future problem drinking. Our
results provide initial evidence that the perceived
conscientiousness of an individual by their peers uniquely
reflects variability in a core neural mechanism supporting
threat responsiveness. These novel patterns further suggest
that incorporating peer-reported measures of personality
into individual differences research can reveal novel
predictive pathways of risk and protection for problem
behaviors.},
Doi = {10.1016/j.neuroimage.2016.10.003},
Key = {fds322497}
}
@article{fds316880,
Author = {Swartz, JR and Hariri, AR and Williamson, DE},
Title = {An epigenetic mechanism links socioeconomic status to
changes in depression-related brain function in high-risk
adolescents.},
Journal = {Molecular psychiatry},
Volume = {22},
Number = {2},
Pages = {209-214},
Year = {2017},
Month = {February},
ISSN = {1359-4184},
Abstract = {Identifying biological mechanisms through which the
experience of adversity emerges as individual risk for
mental illness is an important step toward developing
strategies for personalized treatment and, ultimately,
prevention. Preclinical studies have identified epigenetic
modification of gene expression as one such mechanism.
Recent clinical studies have suggested that epigenetic
modification, particularly methylation of gene regulatory
regions, also acts to shape human brain function associated
with risk for mental illness. However, it is not yet clear
whether differential gene methylation as a function of
adversity contributes to the emergence of individual risk
for mental illness. Using prospective longitudinal
epigenetic, neuroimaging and behavioral data from 132
adolescents, we demonstrate that changes in gene methylation
associated with lower socioeconomic status (SES) predict
changes in risk-related brain function. Specifically, we
find that lower SES during adolescence is associated with an
increase in methylation of the proximal promoter of the
serotonin transporter gene, which predicts greater increases
in threat-related amygdala reactivity. We subsequently
demonstrate that greater increases in amygdala reactivity
moderate the association between a positive family history
for depression and the later manifestation of depressive
symptoms. These initial results suggest a specific
biological mechanism through which adversity contributes to
altered brain function, which in turn moderates the
emergence of general liability as individual risk for mental
illness. If replicated, this prospective pathway may
represent a novel target biomarker for intervention and
prevention among high-risk individuals.},
Doi = {10.1038/mp.2016.82},
Key = {fds316880}
}
@article{fds318715,
Author = {Swartz, JR and Prather, AA and Di Iorio and CR and Bogdan, R and Hariri,
AR},
Title = {A Functional Interleukin-18 Haplotype Predicts Depression
and Anxiety through Increased Threat-Related Amygdala
Reactivity in Women but Not Men.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {42},
Number = {2},
Pages = {419-426},
Year = {2017},
Month = {January},
Abstract = {Common functional polymorphisms in the gene encoding
interleukin-18 (IL18), a cytokine belonging to the IL-1
superfamily that can induce synthesis of several other
cytokines, have been associated with major depressive
episodes following the experience of stressful life events.
The neural mechanisms underlying these associations remain
unexamined. Here we use an imaging genetics strategy to
examine the effects of risk-related IL18 haplotypes
comprising rs187238 and rs1946518 on threat-related amygdala
reactivity and, through an indirect effect, stress-related
symptoms of depression and anxiety in 448 non-Hispanic
Caucasian university students. Analyses indicated that women
but not men possessing an IL18 haplotype comprising both
risk-related alleles evidenced increased threat-related left
centromedial amygdala reactivity relative to other haplotype
groups. Moreover, in women only, increased threat-related
left centromedial amygdala reactivity predicted increased
symptoms of depression and anxiety in individuals also
reporting higher levels of life stress. Path analyses
revealed a significant indirect effect of IL18 risk
haplotype on symptoms of depression and anxiety through
increased threat-related amygdala reactivity. These results
suggest that a common functional IL18 haplotype associated
with heightened proinflammatory responses confers
susceptibility to stress-related depression and anxiety
through effects on threat-related amygdala function, a risk
pathway specific to women. If replicated, these patterns can
inform the search for personalized interventions targeting
neurobiological pathways of risk associated with
inflammation.},
Doi = {10.1038/npp.2016.129},
Key = {fds318715}
}
@article{fds323776,
Author = {Scult, MA and Knodt, AR and Swartz, JR and Brigidi, BD and Hariri,
AR},
Title = {Thinking and Feeling: Individual Differences in Habitual
Emotion Regulation and Stress-Related Mood are Associated
with Prefrontal Executive Control.},
Journal = {Clinical psychological science : a journal of the
Association for Psychological Science},
Volume = {5},
Number = {1},
Pages = {150-157},
Year = {2017},
Month = {January},
Abstract = {Calculating math problems from memory may seem unrelated to
everyday processing of emotions, but they have more in
common than one might think. Prior research highlights the
importance of the dorsolateral prefrontal cortex (dlPFC) in
executive control, intentional emotion regulation, and
experience of dysfunctional mood and anxiety. While it has
been hypothesized that emotion regulation may be related to
'cold' (ie. not emotion-related) executive control, this
assertion has not been tested. We address this gap by
providing evidence that greater dlPFC activity during 'cold'
executive control is associated with increased use of
cognitive reappraisal to regulate emotions in everyday life.
We then demonstrate that in the presence of increased life
stress, increased dlPFC activity is associated with lower
mood and anxiety symptoms and clinical diagnoses.
Collectively, our results encourage ongoing efforts to
understand prefrontal executive control as a possible
intervention target for improving emotion regulation in mood
and anxiety disorders.},
Doi = {10.1177/2167702616654688},
Key = {fds323776}
}
@article{fds318712,
Author = {Scult, MA and Paulli, AR and Mazure, ES and Moffitt, TE and Hariri, AR and Strauman, TJ},
Title = {The association between cognitive function and subsequent
depression: a systematic review and meta-analysis.},
Journal = {Psychol Med},
Volume = {47},
Number = {1},
Pages = {1-17},
Year = {2017},
Month = {January},
Abstract = {Despite a growing interest in understanding the cognitive
deficits associated with major depressive disorder (MDD), it
is largely unknown whether such deficits exist before
disorder onset or how they might influence the severity of
subsequent illness. The purpose of the present study was to
conduct a systematic review and meta-analysis of
longitudinal datasets to determine whether cognitive
function acts as a predictor of later MDD diagnosis or
change in depression symptoms. Eligible studies included
longitudinal designs with baseline measures of cognitive
functioning, and later unipolar MDD diagnosis or symptom
assessment. The systematic review identified 29
publications, representing 34 unique samples, and 121 749
participants, that met the inclusion/exclusion criteria.
Quantitative meta-analysis demonstrated that higher
cognitive function was associated with decreased levels of
subsequent depression (r = -0.088, 95% confidence interval.
-0.121 to -0.054, p < 0.001). However, sensitivity analyses
revealed that this association is likely driven by
concurrent depression symptoms at the time of cognitive
assessment. Our review and meta-analysis indicate that the
association between lower cognitive function and later
depression is confounded by the presence of contemporaneous
depression symptoms at the time of cognitive assessment.
Thus, cognitive deficits predicting MDD likely represent
deleterious effects of subclinical depression symptoms on
performance rather than premorbid risk factors for
disorder.},
Doi = {10.1017/S0033291716002075},
Key = {fds318712}
}
@article{fds318709,
Author = {Pornpattananangkul, N and Hariri, AR and Harada, T and Mano, Y and Komeda, H and Parrish, TB and Sadato, N and Iidaka, T and Chiao,
JY},
Title = {Cultural influences on neural basis of inhibitory
control.},
Journal = {NeuroImage},
Volume = {139},
Pages = {114-126},
Year = {2016},
Month = {October},
Abstract = {Research on neural basis of inhibitory control has been
extensively conducted in various parts of the world. It is
often implicitly assumed that neural basis of inhibitory
control is universally similar across cultures. Here, we
investigated the extent to which culture modulated
inhibitory-control brain activity at both cultural-group and
cultural-value levels of analysis. During fMRI scanning,
participants from different cultural groups (including
Caucasian-Americans and Japanese-Americans living in the
United States and native Japanese living in Japan) performed
a Go/No-Go task. They also completed behavioral surveys
assessing cultural values of behavioral consistency, or the
extent to which one's behaviors in daily life are consistent
across situations. Across participants, the Go/No-Go task
elicited stronger neural activity in several
inhibitory-control areas, such as the inferior frontal gyrus
(IFG) and anterior cingulate cortex (ACC). Importantly, at
the cultural-group level, we found variation in left IFG
(L-IFG) activity that was explained by a cultural region
where participants lived in (as opposed to race).
Specifically, L-IFG activity was stronger for native
Japanese compared to Caucasian- and Japanese-Americans,
while there was no systematic difference in L-IFG activity
between Japanese- and Caucasian-Americans. At the
cultural-value level, we found that participants who valued
being "themselves" across situations (i.e., having high
endorsement of behavioral consistency) elicited stronger
rostral ACC activity during the Go/No-Go task. Altogether,
our findings provide novel insight into how culture
modulates the neural basis of inhibitory
control.},
Doi = {10.1016/j.neuroimage.2016.05.061},
Key = {fds318709}
}
@article{fds318710,
Author = {Nikolova, YS and Swartz, JR and Hariri, AR},
Title = {Can we identify meaningful epigenetic effects on human brain
function and related risk for mental illness?},
Journal = {Epigenomics},
Volume = {8},
Number = {10},
Pages = {1307-1310},
Year = {2016},
Month = {October},
Doi = {10.2217/epi-2016-0099},
Key = {fds318710}
}
@article{fds318711,
Author = {Kragel, PA and Knodt, AR and Hariri, AR and LaBar,
KS},
Title = {Decoding Spontaneous Emotional States in the Human
Brain},
Journal = {PLoS Biol},
Volume = {14},
Number = {9},
Pages = {e2000106},
Publisher = {Public Library of Science},
Year = {2016},
Month = {September},
Abstract = {<title>Author Summary</title> <p>Functional brain imaging
techniques provide a window into neural activity
underpinning diverse cognitive processes, including visual
perception, decision-making, and memory, among many others.
By treating functional imaging data as a pattern-recognition
problem, similar to face- or character-recognition,
researchers have successfully identified patterns of brain
activity that predict specific mental states; for example,
the kind of an object being viewed. Moreover, these methods
are capable of predicting mental states in the absence of
external stimulation. For example, pattern-classifiers
trained on brain responses to visual stimuli can
successfully predict the contents of imagery during sleep.
This research shows that internally mediated brain activity
can be used to infer subjective mental states; however, it
is not known whether more complex emotional mental states
can be decoded from neuroimaging data in the absence of
experimental manipulations. Here we show that brain-based
models of specific emotions can detect individual
differences in mood and emotional traits and are consistent
with self-reports of emotional experience during
intermittent periods of wakeful rest. These findings show
that the brain dynamically fluctuates among multiple
distinct emotional states at rest. More practically, the
results suggest that brain-based models of emotion may help
assess emotional status in clinical settings, particularly
in individuals incapable of providing self-report of their
own emotional experience.</p>},
Doi = {10.1371/journal.pbio.2000106},
Key = {fds318711}
}
@article{fds318713,
Author = {Demers, CH and Drabant Conley and E and Bogdan, R and Hariri,
AR},
Title = {Interactions Between Anandamide and Corticotropin-Releasing
Factor Signaling Modulate Human Amygdala Function and Risk
for Anxiety Disorders: An Imaging Genetics Strategy for
Modeling Molecular Interactions.},
Journal = {Biological psychiatry},
Volume = {80},
Number = {5},
Pages = {356-362},
Year = {2016},
Month = {September},
Abstract = {<h4>Background</h4>Preclinical models reveal that
stress-induced amygdala activity and impairment in fear
extinction reflect reductions in anandamide driven by
corticotropin-releasing factor receptor type 1 (CRF1)
potentiation of the anandamide catabolic enzyme fatty acid
amide hydrolase.<h4>Methods</h4>Here, we provide clinical
translation for the importance of these molecular
interactions using an imaging genetics strategy to examine
whether interactions between genetic polymorphisms
associated with differential anandamide (FAAH rs324420) and
CRF1 (CRHR1 rs110402) signaling modulate amygdala function
and anxiety disorder diagnosis.<h4>Results</h4>Analyses
revealed that individuals with a genetic background
predicting relatively high anandamide and CRF1 signaling
exhibited blunted basolateral amygdala habituation, which
further mediated increased risk for anxiety disorders among
these same individuals.<h4>Conclusions</h4>The convergence
of preclinical and clinical data suggests that interactions
between anandamide and CRF1 represent a fundamental
molecular mechanism regulating amygdala function and
anxiety. Our results further highlight the potential of
imaging genetics to powerfully translate complex preclinical
findings to clinically meaningful human phenotypes.},
Doi = {10.1016/j.biopsych.2015.12.021},
Key = {fds318713}
}
@article{fds318714,
Author = {Waller, R and Corral-Frías, NS and Vannucci, B and Bogdan, R and Knodt,
AR and Hariri, AR and Hyde, LW},
Title = {An oxytocin receptor polymorphism predicts amygdala
reactivity and antisocial behavior in men.},
Journal = {Social cognitive and affective neuroscience},
Volume = {11},
Number = {8},
Pages = {1218-1226},
Year = {2016},
Month = {August},
Abstract = {Variability in oxytocin (OXT) signaling is associated with
individual differences in sex-specific social behavior
across species. The effects of OXT signaling on social
behavior are, in part, mediated through its modulation of
amygdala function. Here, we use imaging genetics to examine
sex-specific effects of three single-nucleotide
polymorphisms in the human oxytocin receptor gene (OXTR;
rs1042778, rs53576 and rs2254298) on threat-related amygdala
reactivity and social behavior in 406 Caucasians. Analyses
revealed that among men but not women, OXTR rs1042778 TT
genotype was associated with increased right amygdala
reactivity to angry facial expressions, which was uniquely
related to higher levels of antisocial behavior among men.
Moderated meditation analysis suggested a trending indirect
effect of OXTR rs1042778 TT genotype on higher antisocial
behavior via increased right amygdala reactivity to angry
facial expressions in men. Our results provide evidence
linking genetic variation in OXT signaling to individual
differences in amygdala function. The results further
suggest that these pathways may be uniquely important in
shaping antisocial behavior in men.},
Doi = {10.1093/scan/nsw042},
Key = {fds318714}
}
@article{fds318716,
Author = {Krystal, JH and Abi-Dargham, A and Akbarian, S and Arnsten, AFT and Barch, DM and Bearden, CE and Braff, DL and Brown, ES and Bullmore, ET and Carlezon, WA and Carter, CS and Cook, EH and Daskalakis, ZJ and DiLeone,
RJ and Duman, RS and Grace, AA and Hariri, AR and Harrison, PJ and Hiroi,
N and Kenny, PJ and Kleinman, JE and Krystal, AD and Lewis, DA and Lipska,
BK and Marder, SR and Mason, GF and Mathalon, DH and McClung, CA and McDougle, CJ and McIntosh, AM and McMahon, FJ and Mirnics, K and Monteggia, LM and Narendran, R and Nestler, EJ and Neumeister, A and O'Donovan, MC and Öngür, D and Pariante, CM and Paulus, MP and Pearlson, G and Phillips, ML and Pine, DS and Pizzagalli, DA and Pletnikov, MV and Ragland, JD and Rapoport, JL and Ressler, KJ and Russo, SJ and Sanacora, G and Sawa, A and Schatzberg, AF and Shaham, Y and Shamay-Tsoory, SG and Sklar, P and State, MW and Stein, MB and Strakowski, SM and Taylor, SF and Turecki, G and Turetsky, BI and Weissman, MM and Zachariou, V and Zarate, CA and Zubieta,
J-K},
Title = {Constance E. Lieber, Theodore R. Stanley, and the Enduring
Impact of Philanthropy on Psychiatry Research.},
Journal = {Biol Psychiatry},
Volume = {80},
Number = {2},
Pages = {84-86},
Year = {2016},
Month = {July},
Doi = {10.1016/j.biopsych.2016.05.004},
Key = {fds318716}
}
@article{fds316881,
Author = {Corral-Frías, NS and Pizzagalli, DA and Carré, JM and Michalski,
LJ and Nikolova, YS and Perlis, RH and Fagerness, J and Lee, MR and Conley,
ED and Lancaster, TM and Haddad, S and Wolf, A and Smoller, JW and Hariri,
AR and Bogdan, R},
Title = {COMT Val(158) Met genotype is associated with reward
learning: a replication study and meta-analysis.},
Journal = {Genes, brain, and behavior},
Volume = {15},
Number = {5},
Pages = {503-513},
Year = {2016},
Month = {June},
ISSN = {1601-1848},
Abstract = {Identifying mechanisms through which individual differences
in reward learning emerge offers an opportunity to
understand both a fundamental form of adaptive responding as
well as etiological pathways through which aberrant reward
learning may contribute to maladaptive behaviors and
psychopathology. One candidate mechanism through which
individual differences in reward learning may emerge is
variability in dopaminergic reinforcement signaling. A
common functional polymorphism within the catechol-O-methyl
transferase gene (COMT; rs4680, Val(158) Met) has been
linked to reward learning, where homozygosity for the Met
allele (linked to heightened prefrontal dopamine function
and decreased dopamine synthesis in the midbrain) has been
associated with relatively increased reward learning. Here,
we used a probabilistic reward learning task to asses
response bias, a behavioral form of reward learning, across
three separate samples that were combined for analyses (age:
21.80 ± 3.95; n = 392; 268 female; European-American: n =
208). We replicate prior reports that COMT rs4680 Met allele
homozygosity is associated with increased reward learning in
European-American participants (β = 0.20, t = 2.75, P <
0.01; ΔR(2) = 0.04). Moreover, a meta-analysis of 4
studies, including the current one, confirmed the
association between COMT rs4680 genotype and reward learning
(95% CI -0.11 to -0.03; z = 3.2; P < 0.01). These results
suggest that variability in dopamine signaling associated
with COMT rs4680 influences individual differences in reward
which may potentially contribute to psychopathology
characterized by reward dysfunction.},
Doi = {10.1111/gbb.12296},
Key = {fds316881}
}
@article{fds251943,
Author = {Nelson, EC and Agrawal, A and Heath, AC and Bogdan, R and Sherva, R and Zhang, B and Al-Hasani, R and Bruchas, MR and Chou, Y-L and Demers, CH and Carey, CE and Conley, ED and Fakira, AK and Farrer, LA and Goate, A and Gordon, S and Henders, AK and Hesselbrock, V and Kapoor, M and Lynskey,
MT and Madden, PAF and Moron, JA and Rice, JP and Saccone, NL and Schwab,
SG and Shand, FL and Todorov, AA and Wallace, L and Wang, T and Wray, NR and Zhou, X and Degenhardt, L and Martin, NG and Hariri, AR and Kranzler,
HR and Gelernter, J and Bierut, LJ and Clark, DJ and Montgomery,
GW},
Title = {Evidence of CNIH3 involvement in opioid dependence.},
Journal = {Molecular psychiatry},
Volume = {21},
Number = {5},
Pages = {608-614},
Year = {2016},
Month = {May},
ISSN = {1359-4184},
Abstract = {Opioid dependence, a severe addictive disorder and major
societal problem, has been demonstrated to be moderately
heritable. We conducted a genome-wide association study in
Comorbidity and Trauma Study data comparing opioid-dependent
daily injectors (N=1167) with opioid misusers who never
progressed to daily injection (N=161). The strongest
associations, observed for CNIH3 single-nucleotide
polymorphisms (SNPs), were confirmed in two independent
samples, the Yale-Penn genetic studies of opioid, cocaine
and alcohol dependence and the Study of Addiction: Genetics
and Environment, which both contain non-dependent opioid
misusers and opioid-dependent individuals. Meta-analyses
found five genome-wide significant CNIH3 SNPs. The A allele
of rs10799590, the most highly associated SNP, was robustly
protective (P=4.30E-9; odds ratio 0.64 (95% confidence
interval 0.55-0.74)). Epigenetic annotation predicts that
this SNP is functional in fetal brain. Neuroimaging data
from the Duke Neurogenetics Study (N=312) provide evidence
of this SNP's in vivo functionality; rs10799590 A allele
carriers displayed significantly greater right amygdala
habituation to threat-related facial expressions, a
phenotype associated with resilience to psychopathology.
Computational genetic analyses of physical dependence on
morphine across 23 mouse strains yielded significant
correlations for haplotypes in CNIH3 and functionally
related genes. These convergent findings support CNIH3
involvement in the pathophysiology of opioid dependence,
complementing prior studies implicating the
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
glutamate system.},
Doi = {10.1038/mp.2015.102},
Key = {fds251943}
}
@article{fds330407,
Author = {Victor, EC and Hariri, AR},
Title = {A neuroscience perspective on sexual risk behavior in
adolescence and emerging adulthood.},
Journal = {Development and psychopathology},
Volume = {28},
Number = {2},
Pages = {471-487},
Year = {2016},
Month = {May},
Abstract = {Late adolescence and emerging adulthood (specifically ages
15-24) represent a period of heightened sexual risk taking
resulting in the greatest annual rates of sexually
transmitted infections and unplanned pregnancies in the US
population. Ongoing efforts to prevent such negative
consequences are likely to benefit from a deepening of our
understanding of biological mechanisms through which sexual
risk taking emerges and biases decision making during this
critical window. Here we present a neuroscience framework
from which a mechanistic examination of sexual risk taking
can be advanced. Specifically, we adapt the
neurodevelopmental triadic model, which outlines how
motivated behavior is governed by three systems: approach,
avoidance, and regulation, to sexual decision making and
subsequent risk behavior. We further propose a testable
hypothesis of the triadic model, wherein relatively
decreased threat-related amygdala reactivity and increased
reward-related ventral striatum reactivity leads to sexual
risk taking, which is particularly exaggerated during
adolescence and young adulthood when there is an
overexpression of dopaminergic neurons coupled with immature
top-down prefrontal cortex regulation. We conclude by
discussing how future research based on our adapted triadic
model can inform ongoing efforts to improve intervention and
prevention efforts.},
Doi = {10.1017/s0954579415001042},
Key = {fds330407}
}
@article{fds313398,
Author = {Gorka, AX and LaBar, KS and Hariri, AR},
Title = {Variability in emotional responsiveness and coping style
during active avoidance as a window onto psychological
vulnerability to stress.},
Journal = {Physiology & behavior},
Volume = {158},
Pages = {90-99},
Year = {2016},
Month = {May},
ISSN = {0031-9384},
Abstract = {Individual differences in coping styles are associated with
psychological vulnerability to stress. Recent animal
research suggests that coping styles reflect trade-offs
between proactive and reactive threat responses during
active avoidance paradigms, with proactive responses
associated with better stress tolerance. Based on these
preclinical findings, we developed a novel instructed active
avoidance paradigm to characterize patterns of proactive and
reactive responses using behavioral, motoric, and autonomic
measures in humans. Analyses revealed significant
inter-individual variability not only in the magnitude of
general emotional responsiveness but also the likelihood to
specifically express proactive or reactive responses. In men
but not women, individual differences in general emotional
responsiveness were linked to increased trait anxiety while
proactive coping style was linked to increased trait
aggression. These patterns are consistent with preclinical
findings and suggest that instructed active avoidance
paradigms may be useful in assessing psychological
vulnerability to stress using objective behavioral
measures.},
Doi = {10.1016/j.physbeh.2016.02.036},
Key = {fds313398}
}
@article{fds251941,
Author = {Nikolova, YS and Knodt, AR and Radtke, SR and Hariri,
AR},
Title = {Divergent responses of the amygdala and ventral striatum
predict stress-related problem drinking in young adults:
possible differential markers of affective and impulsive
pathways of risk for alcohol use disorder.},
Journal = {Molecular psychiatry},
Volume = {21},
Number = {3},
Pages = {348-356},
Year = {2016},
Month = {March},
ISSN = {1359-4184},
Abstract = {Prior work suggests that there may be two distinct pathways
of alcohol use disorder (AUD) risk: one associated with
positive emotion enhancement and behavioral impulsivity, and
another associated with negative emotion relief and coping.
We sought to map these two pathways onto individual
differences in neural reward and threat processing assessed
using blood-oxygen-level-dependent functional magnetic
resonance imaging in a sample of 759 undergraduate students
(426 women, mean age 19.65±1.24 years) participating in the
Duke Neurogenetics Study. We demonstrate that problem
drinking is highest in the context of stress and in those
with one of two distinct neural phenotypes: (1) a
combination of relatively low reward-related activity of the
ventral striatum (VS) and high threat-related reactivity of
the amygdala; or (2) a combination of relatively high VS
activity and low amygdala reactivity. In addition, we
demonstrate that the relationship between stress and problem
alcohol use is mediated by impulsivity, as reflected in
monetary delay discounting rates, for those with high VS-low
amygdala reactivity, and by anxious/depressive
symptomatology for those with the opposite neural risk
phenotype. Across both neural phenotypes, we found that
greater divergence between VS and amygdala reactivity
predicted greater risk for problem drinking. Finally, for
those individuals with the low VS-high amygdala risk
phenotype we found that stress not only predicted the
presence of AUD diagnosis at the time of neuroimaging but
also subsequent problem drinking reported 3 months following
study completion. These results offer new insight into the
neural basis of AUD risk and suggest novel biological
targets for early individualized treatment or
prevention.},
Doi = {10.1038/mp.2015.85},
Key = {fds251941}
}
@article{fds314439,
Author = {Baranger, DAA and Ifrah, C and Prather, AA and Carey, CE and Corral-Frías, NS and Drabant Conley and E and Hariri, AR and Bogdan,
R},
Title = {PER1 rs3027172 Genotype Interacts with Early Life Stress to
Predict Problematic Alcohol Use, but Not Reward-Related
Ventral Striatum Activity.},
Journal = {Frontiers in psychology},
Volume = {7},
Pages = {464},
Year = {2016},
Month = {January},
Abstract = {Increasing evidence suggests that the circadian and stress
regulatory systems contribute to alcohol use disorder (AUD)
risk, which may partially arise through effects on
reward-related neural function. The C allele of the PER1
rs3027172 single nucleotide polymorphism (SNP) reduces PER1
expression in cells incubated with cortisol and has been
associated with increased risk for adult AUD and problematic
drinking among adolescents exposed to high levels of
familial psychosocial adversity. Using data from
undergraduate students who completed the ongoing Duke
Neurogenetics Study (DNS) (n = 665), we tested whether
exposure to early life stress (ELS; Childhood Trauma
Questionnaire) moderates the association between rs3027172
genotype and later problematic alcohol use (Alcohol Use
Disorders Identification Test) as well as ventral striatum
(VS) reactivity to reward (card-guessing task while
functional magnetic resonance imaging data were acquired).
Initial analyses found that PER1 rs3027172 genotype
interacted with ELS to predict both problematic drinking and
VS reactivity; minor C allele carriers, who were also
exposed to elevated ELS reported greater problematic
drinking and exhibited greater ventral striatum reactivity
to reward-related stimuli. When gene × covariate and
environment × covariate interactions were controlled for,
the interaction predicting problematic alcohol use remained
significant (p < 0.05, corrected) while the interaction
predicting VS reactivity was no longer significant. These
results extend our understanding of relationships between
PER1 genotype, ELS, and problematic alcohol use, and serve
as a cautionary tale on the importance of controlling for
potential confounders in studies of moderation including
gene × environment interactions.},
Doi = {10.3389/fpsyg.2016.00464},
Key = {fds314439}
}
@article{fds330408,
Author = {Bogdan, R and Pagliaccio, D and Baranger, DA and Hariri,
AR},
Title = {Genetic Moderation of Stress Effects on Corticolimbic
Circuitry.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {41},
Number = {1},
Pages = {275-296},
Year = {2016},
Month = {January},
Abstract = {Stress exposure is associated with individual differences in
corticolimbic structure and function that often mirror
patterns observed in psychopathology. Gene x environment
interaction research suggests that genetic variation
moderates the impact of stress on risk for psychopathology.
On the basis of these findings, imaging genetics, which
attempts to link variability in DNA sequence and structure
to neural phenotypes, has begun to incorporate measures of
the environment. This research paradigm, known as imaging
gene x environment interaction (iGxE), is beginning to
contribute to our understanding of the neural mechanisms
through which genetic variation and stress increase
psychopathology risk. Although awaiting replication,
evidence suggests that genetic variation within the
canonical neuroendocrine stress hormone system, the
hypothalamic-pituitary-adrenal axis, contributes to
variability in stress-related corticolimbic structure and
function, which, in turn, confers risk for psychopathology.
For iGxE research to reach its full potential it will have
to address many challenges, of which we discuss: (i) small
effects, (ii) measuring the environment and neural
phenotypes, (iii) the absence of detailed mechanisms, and
(iv) incorporating development. By actively addressing these
challenges, iGxE research is poised to help identify the
neural mechanisms underlying genetic and environmental
associations with psychopathology.},
Doi = {10.1038/npp.2015.216},
Key = {fds330408}
}
@article{fds365877,
Author = {Hyde, LW and Shaw, DS and Murray, L and Gard, A and Hariri, AR and Forbes,
EE},
Title = {Dissecting the Role of Amygdala Reactivity in Antisocial
Behavior in a Sample of Young, Low-Income, Urban
Men},
Journal = {Clinical Psychological Science},
Volume = {4},
Number = {3},
Pages = {527-544},
Year = {2016},
Month = {January},
Abstract = {Neuroimaging has suggested that amygdala reactivity to
emotional facial expressions is associated with antisocial
behavior (AB), particularly among those high on
callous–unemotional (CU) traits. To investigate this
association and potential moderators of this relationship,
including task/stimuli effects, subregional anatomy of the
amygdala, and participant race, we used fMRI in a sample of
167 racially diverse 20-year-old men from low-income
families. We found that AB, but not CU traits, was
negatively related to amygdala reactivity to fearful faces.
This result was specific to fearful faces and strongest in
the centromedial subregion of the amygdala. Arrest record
was positively related to basolateral amygdala reactivity to
fearful and angry faces. Results were strongest among those
identified as African American and not present in those
identified as European American. Our findings suggest
substantial complexity in the relationship between amygdala
function and AB reflecting moderating effects of task
stimulus, subregional anatomy, and race.},
Doi = {10.1177/2167702615614511},
Key = {fds365877}
}
@article{fds318717,
Author = {Carey, CE and Agrawal, A and Zhang, B and Conley, ED and Degenhardt, L and Heath, AC and Li, D and Lynskey, MT and Martin, NG and Montgomery, GW and Wang, T and Bierut, LJ and Hariri, AR and Nelson, EC and Bogdan,
R},
Title = {Monoacylglycerol lipase (MGLL) polymorphism rs604300
interacts with childhood adversity to predict cannabis
dependence symptoms and amygdala habituation: Evidence from
an endocannabinoid system-level analysis.},
Journal = {Journal of abnormal psychology},
Volume = {124},
Number = {4},
Pages = {860-877},
Year = {2015},
Month = {November},
Abstract = {Despite evidence for heritable variation in cannabis
involvement and the discovery of cannabinoid receptors and
their endogenous ligands, no consistent patterns have
emerged from candidate endocannabinoid (eCB) genetic
association studies of cannabis involvement. Given
interactions between eCB and stress systems and associations
between childhood stress and cannabis involvement, it may be
important to consider childhood adversity in the context of
eCB-related genetic variation. We employed a system-level
gene-based analysis of data from the Comorbidity and Trauma
Study (N = 1,558) to examine whether genetic variation in
six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism:
MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual
abuse (CSA) predict cannabis dependence symptoms.
Significant interactions with CSA emerged for MGLL at the
gene level (p = .009), and for rs604300 within MGLL (ΔR2 =
.007, p < .001), the latter of which survived SNP-level
Bonferroni correction and was significant in an additional
sample with similar directional effects (N = 859; ΔR2 =
.005, p = .026). Furthermore, in a third sample (N = 312),
there was evidence that rs604300 genotype interacts with
early life adversity to predict threat-related basolateral
amygdala habituation, a neural phenotype linked to the eCB
system and addiction (ΔR2 = .013, p = .047). Rs604300 may
be related to epigenetic modulation of MGLL expression.
These results are consistent with rodent models implicating
2-arachidonoylglycerol (2-AG), an endogenous cannabinoid
metabolized by the enzyme encoded by MGLL, in the etiology
of stress adaptation related to cannabis dependence, but
require further replication.},
Doi = {10.1037/abn0000079},
Key = {fds318717}
}
@article{fds251944,
Author = {Hanson, JL and Hariri, AR and Williamson, DE},
Title = {Blunted Ventral Striatum Development in Adolescence Reflects
Emotional Neglect and Predicts Depressive
Symptoms.},
Journal = {Biological psychiatry},
Volume = {78},
Number = {9},
Pages = {598-605},
Year = {2015},
Month = {November},
ISSN = {0006-3223},
Abstract = {<h4>Background</h4>Emotional neglect is associated with
multiple negative outcomes, particularly increased risk for
depression. Motivated by increasing evidence of
reward-related ventral striatum (VS) dysfunction in
depression, we investigated the role of developmental
changes in VS activity on the emergence of depressive
symptomatology as a function of emotional
neglect.<h4>Methods</h4>We examined relationships between
longitudinal neuroimaging of reward-related VS activity,
assessments of mood, and measures of emotional neglect in
106 participants first scanned between ages 11 to 15 and
then 2 years later.<h4>Results</h4>We found that greater
levels of emotional neglect were associated with blunted
development of reward-related VS activity between the first
and second assessments (as indexed by lower residualized
change scores). Additionally, we found that decreases in
this reward-related VS activity were related to greater
depressive symptomatology and partially mediated the
association between emotional neglect and subsequent
depressive symptomatology.<h4>Conclusions</h4>Our results
provide an important demonstration that blunted development
of reward-related VS activity as a function of emotional
neglect predicts the emergence of depressive symptoms in
adolescents. Further, our results are consistent with
emerging evidence for the importance of reward-related VS
dysfunction in the etiology and pathophysiology of
depression. These results are a first step toward developing
the ability to predict, prevent, and treat stress-related
psychopathology through the targeting of specific neural
phenotypes.},
Doi = {10.1016/j.biopsych.2015.05.010},
Key = {fds251944}
}
@article{fds330409,
Author = {Hanson, JL and Knodt, AR and Brigidi, BD and Hariri,
AR},
Title = {Lower structural integrity of the uncinate fasciculus is
associated with a history of child maltreatment and future
psychological vulnerability to stress.},
Journal = {Development and psychopathology},
Volume = {27},
Number = {4 Pt 2},
Pages = {1611-1619},
Year = {2015},
Month = {November},
Abstract = {The experience of child maltreatment is a significant risk
factor for the development of later internalizing disorders
such as depression and anxiety. This risk is particularly
heightened after exposure to additional, more
contemporaneous stress. While behavioral evidence exists for
such "stress sensitization," little is known about the
mechanisms mediating such relationships, particularly within
the brain. Here we report that the experience of child
maltreatment independent of recent life stress, gender, and
age is associated with reduced structural integrity of the
uncinate fasciculus, a major white matter pathway between
the amygdala and ventromedial prefrontal cortex, in young
adults. We further demonstrate that individuals with lower
uncinate fasciculus integrity at baseline who subsequently
experience stressful life events report higher levels of
internalizing symptomatology at follow-up. Our findings
suggest a novel neurobiological mechanism linking child
maltreatment with later internalizing symptoms, specifically
altered structural connectivity within the brain's
threat-detection and emotion-regulation circuitry.},
Doi = {10.1017/s0954579415000978},
Key = {fds330409}
}
@article{fds315132,
Author = {Hanson, JL and Albert, WD and Iselin, AR and Carré, JM and Dodge, KA and Hariri, AR},
Title = {Cumulative Stress In Childhood is Associated with Blunted
Reward-Related Brain Activity In Adulthood},
Journal = {Social Cognitive and Affective Neuroscience},
Volume = {11},
Number = {3},
Pages = {405-412},
Year = {2015},
Month = {October},
ISSN = {1749-5016},
url = {http://hdl.handle.net/10161/10777 Duke open access
repository},
Abstract = {Early life stress (ELS) is strongly associated with negative
outcomes in adulthood, including reduced motivation and
increased negative mood. The mechanisms mediating these
relations, however, are poorly understood. We examined the
relation between exposure to ELS and reward-related brain
activity, which is known to predict motivation and mood, at
age 26, in a sample followed since kindergarten with annual
assessments. Using functional neuroimaging, we assayed
individual differences in the activity of the ventral
striatum (VS) during the processing of monetary rewards
associated with a simple card-guessing task, in a sample of
72 male participants. We examined associations between a
cumulative measure of ELS exposure and VS activity in
adulthood. We found that greater levels of cumulative stress
during childhood and adolescence predicted lower
reward-related VS activity in adulthood. Extending this
general developmental pattern, we found that exposure to
stress early in development (between kindergarten and grade
3) was significantly associated with variability in adult VS
activity. Our results provide an important demonstration
that cumulative life stress, especially during this
childhood period, is associated with blunted reward-related
VS activity in adulthood. These differences suggest
neurobiological pathways through which a history of ELS may
contribute to reduced motivation and increased negative
mood.},
Doi = {10.1093/scan/nsv124},
Key = {fds315132}
}
@article{fds251937,
Author = {Hariri, AR and Holmes, A},
Title = {Finding translation in stress research.},
Journal = {Nature neuroscience},
Volume = {18},
Number = {10},
Pages = {1347-1352},
Year = {2015},
Month = {October},
ISSN = {1097-6256},
Abstract = {In our ongoing efforts to advance understanding of human
diseases, translational research across rodents and humans
on stress-related mental disorders stands out as a field
that is producing discoveries that illuminate mechanisms of
risk and pathophysiology at a brisk rate. Here we offer a
Perspective on how a productive translational research
dialog between preclinical models and clinical studies of
these disorders is being powered by an ever-developing
appreciation of the shared neural circuits and genetic
architecture that moderate the response to stress across
species. Working from these deep foundations, we discuss the
approaches, both traditional and innovative, that have the
potential to deliver a new generation of risk biomarkers and
therapeutic strategies for stress-related
disorders.},
Doi = {10.1038/nn.4111},
Key = {fds251937}
}
@article{fds291135,
Author = {Scult, MA and Trampush, JW and Zheng, F and Conley, ED and Lencz, T and Malhotra, AK and Dickinson, D and Weinberger, DR and Hariri,
AR},
Title = {A Common Polymorphism in SCN2A Predicts General Cognitive
Ability through Effects on PFC Physiology.},
Journal = {Journal of cognitive neuroscience},
Volume = {27},
Number = {9},
Pages = {1766-1774},
Year = {2015},
Month = {September},
ISSN = {0898-929X},
Abstract = {Here we provide novel convergent evidence across three
independent cohorts of healthy adults (n = 531),
demonstrating that a common polymorphism in the gene
encoding the α2 subunit of neuronal voltage-gated type II
sodium channels (SCN2A) predicts human general cognitive
ability or "g." Using meta-analysis, we demonstrate that the
minor T allele of a common polymorphism (rs10174400) in
SCN2A is associated with significantly higher "g"
independent of gender and age. We further demonstrate using
resting-state fMRI data from our discovery cohort (n = 236)
that this genetic advantage may be mediated by increased
capacity for information processing between the dorsolateral
PFC and dorsal ACC, which support higher cognitive
functions. Collectively, these findings fill a gap in our
understanding of the genetics of general cognitive ability
and highlight a specific neural mechanism through which a
common polymorphism shapes interindividual variation in
"g."},
Doi = {10.1162/jocn_a_00826},
Key = {fds291135}
}
@article{fds251948,
Author = {Nikolova, YS and Hariri, AR},
Title = {Can we observe epigenetic effects on human brain
function?},
Journal = {Trends in cognitive sciences},
Volume = {19},
Number = {7},
Pages = {366-373},
Year = {2015},
Month = {July},
ISSN = {1364-6613},
Abstract = {Imaging genetics has identified many contributions of DNA
sequence variation to individual differences in brain
function, behavior, and risk for psychopathology. Recent
studies have extended this work beyond the genome by mapping
epigenetic differences, specifically gene methylation in
peripherally assessed DNA, onto variability in behaviorally
and clinically relevant brain function. These data have
generated understandable enthusiasm for the potential of
such research to illuminate biological mechanisms of risk.
We use our research on the effects of genetic and epigenetic
variation in the human serotonin transporter on brain
function to generate a guardedly optimistic opinion that the
available data encourage continued research in this
direction, and suggest strategies to promote faster
progress.},
Doi = {10.1016/j.tics.2015.05.003},
Key = {fds251948}
}
@article{fds251949,
Author = {Trampush, JW and Lencz, T and Knowles, E and Davies, G and Guha, S and Pe'er, I and Liewald, DC and Starr, JM and Djurovic, S and Melle, I and Sundet, K and Christoforou, A and Reinvang, I and Mukherjee, S and DeRosse, P and Lundervold, A and Steen, VM and John, M and Espeseth, T and Räikkönen, K and Widen, E and Palotie, A and Eriksson, JG and Giegling, I and Konte, B and Ikeda, M and Roussos, P and Giakoumaki, S and Burdick, KE and Payton, A and Ollier, W and Horan, M and Scult, M and Dickinson, D and Straub, RE and Donohoe, G and Morris, D and Corvin, A and Gill, M and Hariri, A and Weinberger, DR and Pendleton, N and Iwata, N and Darvasi, A and Bitsios, P and Rujescu, D and Lahti, J and Le Hellard and S and Keller, MC and Andreassen, OA and Deary, IJ and Glahn, DC and Malhotra,
AK},
Title = {Independent evidence for an association between general
cognitive ability and a genetic locus for educational
attainment.},
Journal = {American journal of medical genetics. Part B,
Neuropsychiatric genetics : the official publication of the
International Society of Psychiatric Genetics},
Volume = {168B},
Number = {5},
Pages = {363-373},
Year = {2015},
Month = {July},
ISSN = {1552-4841},
Abstract = {Cognitive deficits and reduced educational achievement are
common in psychiatric illness; understanding the genetic
basis of cognitive and educational deficits may be
informative about the etiology of psychiatric disorders. A
recent, large genome-wide association study (GWAS) reported
a genome-wide significant locus for years of education,
which subsequently demonstrated association to general
cognitive ability ("g") in overlapping cohorts. The current
study was designed to test whether GWAS hits for educational
attainment are involved in general cognitive ability in an
independent, large-scale collection of cohorts. Using
cohorts in the Cognitive Genomics Consortium (COGENT; up to
20,495 healthy individuals), we examined the relationship
between g and variants associated with educational
attainment. We next conducted meta-analyses with 24,189
individuals with neurocognitive data from the educational
attainment studies, and then with 53,188 largely independent
individuals from a recent GWAS of cognition. A SNP
(rs1906252) located at chromosome 6q16.1, previously
associated with years of schooling, was significantly
associated with g (P = 1.47 × 10(-4) ) in COGENT.
The first joint analysis of 43,381 non-overlapping
individuals for this a priori-designated locus was strongly
significant (P = 4.94 × 10(-7) ), and the second
joint analysis of 68,159 non-overlapping individuals was
even more robust (P = 1.65 × 10(-9) ). These
results provide independent replication, in a large-scale
dataset, of a genetic locus associated with cognitive
function and education. As sample sizes grow, cognitive GWAS
will identify increasing numbers of associated loci, as has
been accomplished in other polygenic quantitative traits,
which may be relevant to psychiatric illness.},
Doi = {10.1002/ajmg.b.32319},
Key = {fds251949}
}
@article{fds251938,
Author = {Telch, MJ and Beevers, CG and Rosenfield, D and Lee, H-J and Reijntjes,
A and Ferrell, RE and Hariri, AR},
Title = {5-HTTLPR genotype potentiates the effects of war zone
stressors on the emergence of PTSD, depressive and anxiety
symptoms in soldiers deployed to iraq.},
Journal = {World psychiatry : official journal of the World Psychiatric
Association (WPA)},
Volume = {14},
Number = {2},
Pages = {198-206},
Year = {2015},
Month = {June},
ISSN = {1723-8617},
Abstract = {Exposure to war zone stressors is common, yet only a
minority of soldiers experience clinically meaningful
disturbance in psychological function. Identification of
biomarkers that predict vulnerability to war zone stressors
is critical for developing more effective treatment and
prevention strategies not only in soldiers but also in
civilians who are exposed to trauma. We investigated the
role of the serotonin transporter linked polymorphic region
(5-HTTLPR) genotype in predicting the emergence of
post-traumatic stress disorder (PTSD), depressive and
anxiety symptoms as a function of war zone stressors. A
prospective cohort of 133 U.S. Army soldiers with no prior
history of deployment to a war zone, who were scheduled to
deploy to Iraq, was recruited. Multilevel regression models
were used to investigate associations between 5-HTTLPR
genotype, level of war zone stressors, and reported symptoms
of PTSD, depression and anxiety while deployed to Iraq.
Level of war zone stressors was associated with symptoms of
PTSD, depression and anxiety. Consistent with its effects on
stress responsiveness, 5-HTTLPR genotype moderated the
relationship between level of war zone stressors and
symptoms of emotional disturbance. Specifically, soldiers
carrying one or two low functioning alleles (S or LG )
reported heightened symptoms of PTSD, depression and anxiety
in response to increased levels of exposure to war zone
stressors, relative to soldiers homozygous for the high
functioning allele (LA ). These data suggest that 5-HTTLPR
genotype moderates individual sensitivity to war zone
stressors and the expression of emotional disturbance
including PTSD symptoms. Replication of this association
along with identification of other genetic moderators of
risk can inform the development of biomarkers that can
predict relative resilience vs. vulnerability to
stress.},
Doi = {10.1002/wps.20215},
Key = {fds251938}
}
@article{fds251939,
Author = {Arloth, J and Bogdan, R and Weber, P and Frishman, G and Menke, A and Wagner, KV and Balsevich, G and Schmidt, MV and Karbalai, N and Czamara,
D and Altmann, A and Trümbach, D and Wurst, W and Mehta, D and Uhr, M and Klengel, T and Erhardt, A and Carey, CE and Conley, ED and Major
Depressive Disorder Working Group of the Psychiatric
Genomics Consortium (PGC), and Ruepp, A and Müller-Myhsok, B and Hariri, AR and Binder, EB and Major Depressive Disorder Working
Group of the Psychiatric Genomics Consortium
PGC},
Title = {Genetic Differences in the Immediate Transcriptome Response
to Stress Predict Risk-Related Brain Function and
Psychiatric Disorders.},
Journal = {Neuron},
Volume = {86},
Number = {5},
Pages = {1189-1202},
Year = {2015},
Month = {June},
ISSN = {0896-6273},
Abstract = {Depression risk is exacerbated by genetic factors and stress
exposure; however, the biological mechanisms through which
these factors interact to confer depression risk are poorly
understood. One putative biological mechanism implicates
variability in the ability of cortisol, released in response
to stress, to trigger a cascade of adaptive genomic and
non-genomic processes through glucocorticoid receptor (GR)
activation. Here, we demonstrate that common genetic
variants in long-range enhancer elements modulate the
immediate transcriptional response to GR activation in human
blood cells. These functional genetic variants increase risk
for depression and co-heritable psychiatric disorders.
Moreover, these risk variants are associated with
inappropriate amygdala reactivity, a transdiagnostic
psychiatric endophenotype and an important stress hormone
response trigger. Network modeling and animal experiments
suggest that these genetic differences in GR-induced
transcriptional activation may mediate the risk for
depression and other psychiatric disorders by altering a
network of functionally related stress-sensitive genes in
blood and brain.},
Doi = {10.1016/j.neuron.2015.05.034},
Key = {fds251939}
}
@article{fds251940,
Author = {Victor, EC and Sansosti, AA and Bowman, HC and Hariri,
AR},
Title = {Differential patterns of amygdala and ventral striatum
activation predict gender-specific changes in sexual risk
behavior.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {35},
Number = {23},
Pages = {8896-8900},
Year = {2015},
Month = {June},
ISSN = {0270-6474},
Abstract = {Although the initiation of sexual behavior is common among
adolescents and young adults, some individuals express this
behavior in a manner that significantly increases their risk
for negative outcomes including sexually transmitted
infections. Based on accumulating evidence, we have
hypothesized that increased sexual risk behavior reflects,
in part, an imbalance between neural circuits mediating
approach and avoidance in particular as manifest by
relatively increased ventral striatum (VS) activity and
relatively decreased amygdala activity. Here, we test our
hypothesis using data from seventy 18- to 22-year-old
university students participating in the Duke Neurogenetics
Study. We found a significant three-way interaction between
amygdala activation, VS activation, and gender predicting
changes in the number of sexual partners over time. Although
relatively increased VS activation predicted greater
increases in sexual partners for both men and women, the
effect in men was contingent on the presence of relatively
decreased amygdala activation and the effect in women was
contingent on the presence of relatively increased amygdala
activation. These findings suggest unique gender differences
in how complex interactions between neural circuit function
contributing to approach and avoidance may be expressed as
sexual risk behavior in young adults. As such, our findings
have the potential to inform the development of novel,
gender-specific strategies that may be more effective at
curtailing sexual risk behavior.},
Doi = {10.1523/jneurosci.0737-15.2015},
Key = {fds251940}
}
@article{fds251946,
Author = {Gorka, AX and Norman, RE and Radtke, SR and Carré, JM and Hariri,
AR},
Title = {Anterior cingulate cortex gray matter volume mediates an
association between 2D:4D ratio and trait aggression in
women but not men.},
Journal = {Psychoneuroendocrinology},
Volume = {56},
Pages = {148-156},
Year = {2015},
Month = {June},
ISSN = {0306-4530},
Abstract = {Previous research demonstrates that prenatal testosterone
exposure increases aggression, possibly through its effects
on the structure and function of neural circuits supporting
threat detection and emotion regulation. Here we examined
associations between regional gray matter volume, trait
aggression, and the ratio of the second and fourth digit of
the hand (2D:4D ratio) as a putative index of prenatal
testosterone exposure in 464 healthy young adult volunteers.
Our analyses revealed a significant positive correlation
between 2D:4D ratio and gray matter volume of the dorsal
anterior cingulate cortex (dACC), a brain region supporting
emotion regulation, conflict monitoring, and behavioral
inhibition. Subsequent analyses demonstrated that reduced
(i.e., masculinized) gray matter volume in the dACC mediated
the relationship between 2D:4D ratio and aggression in
women, but not men. Expanding on this gender-specific
mediation, additional analyses demonstrated that the shared
variance between 2D:4D ratio, dACC gray matter volume, and
aggression in women reflected the tendency to engage in
cognitive reappraisal of emotionally provocative stimuli.
Our results provide novel evidence that 2D:4D ratio is
associated with masculinization of dACC gray matter volume,
and that this neural phenotype mediates, in part, the
expression of trait aggression in women.},
Doi = {10.1016/j.psyneuen.2015.03.004},
Key = {fds251946}
}
@article{fds251953,
Author = {Kochunov, P and Jahanshad, N and Marcus, D and Winkler, A and Sprooten,
E and Nichols, TE and Wright, SN and Hong, LE and Patel, B and Behrens, T and Jbabdi, S and Andersson, J and Lenglet, C and Yacoub, E and Moeller, S and Auerbach, E and Ugurbil, K and Sotiropoulos, SN and Brouwer, RM and Landman, B and Lemaitre, H and den Braber, A and Zwiers, MP and Ritchie,
S and van Hulzen, K and Almasy, L and Curran, J and deZubicaray, GI and Duggirala, R and Fox, P and Martin, NG and McMahon, KL and Mitchell, B and Olvera, RL and Peterson, C and Starr, J and Sussmann, J and Wardlaw, J and Wright, M and Boomsma, DI and Kahn, R and de Geus, EJC and Williamson,
DE and Hariri, A and van 't Ent, D and Bastin, ME and McIntosh, A and Deary, IJ and Hulshoff Pol and HE and Blangero, J and Thompson, PM and Glahn, DC and Van Essen and DC},
Title = {Heritability of fractional anisotropy in human white matter:
a comparison of Human Connectome Project and ENIGMA-DTI
data.},
Journal = {NeuroImage},
Volume = {111},
Pages = {300-311},
Year = {2015},
Month = {May},
ISSN = {1053-8119},
Abstract = {The degree to which genetic factors influence brain
connectivity is beginning to be understood. Large-scale
efforts are underway to map the profile of genetic effects
in various brain regions. The NIH-funded Human Connectome
Project (HCP) is providing data valuable for analyzing the
degree of genetic influence underlying brain connectivity
revealed by state-of-the-art neuroimaging methods. We
calculated the heritability of the fractional anisotropy
(FA) measure derived from diffusion tensor imaging (DTI)
reconstruction in 481 HCP subjects (194/287 M/F) consisting
of 57/60 pairs of mono- and dizygotic twins, and 246
siblings. FA measurements were derived using (Enhancing
NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI
protocols and heritability estimates were calculated using
the SOLAR-Eclipse imaging genetic analysis package. We
compared heritability estimates derived from HCP data to
those publicly available through the ENIGMA-DTI consortium,
which were pooled together from five-family based studies
across the US, Europe, and Australia. FA measurements from
the HCP cohort for eleven major white matter tracts were
highly heritable (h(2)=0.53-0.90, p<10(-5)), and were
significantly correlated with the joint-analytical estimates
from the ENIGMA cohort on the tract and voxel-wise levels.
The similarity in regional heritability suggests that the
additive genetic contribution to white matter microstructure
is consistent across populations and imaging acquisition
parameters. It also suggests that the overarching genetic
influence provides an opportunity to define a common genetic
search space for future gene-discovery studies. Uniquely,
the measurements of additive genetic contribution performed
in this study can be repeated using online genetic analysis
tools provided by the HCP ConnectomeDB web
application.},
Doi = {10.1016/j.neuroimage.2015.02.050},
Key = {fds251953}
}
@article{fds251950,
Author = {Gorka, AX and Knodt, AR and Hariri, AR},
Title = {Basal forebrain moderates the magnitude of task-dependent
amygdala functional connectivity.},
Journal = {Social cognitive and affective neuroscience},
Volume = {10},
Number = {4},
Pages = {501-507},
Year = {2015},
Month = {April},
ISSN = {1749-5016},
Abstract = {Animal studies reveal that the amygdala promotes attention
and emotional memory, in part, by driving activity in
downstream target regions including the prefrontal cortex
(PFC) and hippocampus. Prior work has demonstrated that the
amygdala influences these regions directly through
monosynaptic glutamatergic signaling, and indirectly by
driving activity of the cholinergic basal forebrain and
subsequent downstream acetylcholine release. Yet to date, no
work has addressed the functional relevance of the
cholinergic basal forebrain in facilitating signaling from
the amygdala in humans. We set out to determine how blood
oxygen level-dependent signal within the amygdala and
cholinergic basal forebrain interact to predict neural
responses within downstream targets. Here, we use functional
connectivity analyses to demonstrate that the cholinergic
basal forebrain moderates increased amygdala connectivity
with both the PFC and the hippocampus during the processing
of biologically salient stimuli in humans. We further
demonstrate that functional variation within the choline
transporter gene predicts the magnitude of this modulatory
effect. Collectively, our results provide novel evidence for
the importance of cholinergic signaling in modulating neural
pathways supporting arousal, attention and memory in humans.
Further, our results may shed light on prior association
studies linking functional variation within the choline
transporter gene and diagnoses of major depression and
attention-deficit hyperactivity disorder.},
Doi = {10.1093/scan/nsu080},
Key = {fds251950}
}
@article{fds251952,
Author = {Swartz, JR and Williamson, DE and Hariri, AR},
Title = {Developmental change in amygdala reactivity during
adolescence: effects of family history of depression and
stressful life events.},
Journal = {The American journal of psychiatry},
Volume = {172},
Number = {3},
Pages = {276-283},
Year = {2015},
Month = {March},
ISSN = {0002-953X},
Abstract = {<h4>Objective</h4>Although heightened amygdala reactivity is
observed in patients with major depression, two critical
gaps in our knowledge remain. First, it is unclear whether
heightened amygdala reactivity is a premorbid vulnerability
or a consequence of the disorder. Second, it is unknown how
and when this neural phenotype develops. The authors sought
to address these gaps by evaluating developmental change in
threat-related amygdala reactivity in adolescents at high or
low risk for depression based on family history, before
onset of disorder.<h4>Method</h4>At baseline and again 2
years later, adolescents (initially 11-15 years of age)
participated in a functional MRI paradigm that elicited
threat-related amygdala reactivity. After quality control,
data were available for 232 adolescents at wave 1 and 197
adolescents at wave 2; longitudinal data meeting quality
control at both waves were available for 157 of these
participants. Change in amygdala reactivity was assessed as
a function of family history of depression and severity of
stressful life events.<h4>Results</h4>Threat-related
amygdala reactivity increased with age in participants with
a positive family history regardless of the severity of life
stress reported, and it increased in adolescents with a
negative family history who reported relatively severe life
stress. These changes in amygdala reactivity with age
occurred in the absence of clinical disorder or increases in
depressive symptoms.<h4>Conclusions</h4>These results
suggest that heightened amygdala reactivity emerges during
adolescence, prior to the development of depression, as a
function of familial risk or, in the absence of familial
risk, stressful life events.},
Doi = {10.1176/appi.ajp.2014.14020195},
Key = {fds251952}
}
@misc{fds251945,
Author = {Faig, KE and Nikolova, YS and Hariri, AR},
Title = {Genetic Neuroimaging of Social Perception},
Volume = {3},
Pages = {97-105},
Booktitle = {Brain Mapping: An Encyclopedic Reference},
Publisher = {Elsevier},
Year = {2015},
Month = {February},
ISBN = {9780123973160},
Doi = {10.1016/B978-0-12-397025-1.00161-5},
Key = {fds251945}
}
@article{fds251955,
Author = {Swartz, J and Knodt, A and Radtke, S and Hariri, A},
Title = {A Neural Biomarker of Psychological Vulnerability to Future
Life Stress},
Journal = {Neuron},
Volume = {85},
Number = {3},
Pages = {505-511},
Publisher = {Elsevier},
Year = {2015},
Month = {February},
ISSN = {0896-6273},
url = {http://hdl.handle.net/10161/9483 Duke open access
repository},
Abstract = {We all experience a host of common life stressors such as
the death of a family member, medical illness, and financial
uncertainty. While most of us are resilient to such
stressors, continuing to function normally, for a subset of
individuals, experiencing these stressors increases the
likelihood of developing treatment-resistant, chronic
psychological problems, including depression and anxiety. It
is thus paramount to identify predictive markers of risk,
particularly those reflecting fundamental biological
processes that can be targets for intervention and
prevention. Using data from a longitudinal study of 340
healthy young adults, we demonstrate that individual
differences in threat-related amygdala reactivity predict
psychological vulnerability to life stress occurring as much
as 1 to 4 years later. These results highlight a readily
assayed biomarker, threat-related amygdala reactivity, which
predicts psychological vulnerability to commonly experienced
stressors and represents a discrete target for intervention
and prevention.},
Doi = {10.1016/j.neuron.2014.12.055},
Key = {fds251955}
}
@article{fds251951,
Author = {Corral-Frías, NS and Nikolova, YS and Michalski, LJ and Baranger,
DAA and Hariri, AR and Bogdan, R},
Title = {Stress-related anhedonia is associated with ventral striatum
reactivity to reward and transdiagnostic psychiatric
symptomatology.},
Journal = {Psychological medicine},
Volume = {45},
Number = {12},
Pages = {2605-2617},
Year = {2015},
Month = {January},
ISSN = {0033-2917},
Abstract = {<h4>Background</h4>Early life stress (ELS) is consistently
associated with increased risk for subsequent
psychopathology. Individual differences in neural response
to reward may confer vulnerability to stress-related
psychopathology. Using data from the ongoing Duke
Neurogenetics Study, the present study examined whether
reward-related ventral striatum (VS) reactivity moderates
the relationship between retrospectively reported ELS and
anhedonic symptomatology. We further assessed whether
individual differences in reward-related VS reactivity were
associated with other depressive symptoms and problematic
alcohol use via stress-related anhedonic symptoms and
substance use-associated coping.<h4>Method</h4>Blood oxygen
level-dependent functional magnetic resonance imaging (fMRI)
was collected while participants (n = 906) completed a
card-guessing task, which robustly elicits VS reactivity.
ELS, anhedonic symptoms, other depressive symptoms, coping
behavior, and alcohol use behavior were assessed with
self-report questionnaires. Linear regressions were run to
examine whether VS reactivity moderated the relationship
between ELS and anhedonic symptoms. Structural equation
models examined whether this moderation was indirectly
associated with other depression symptoms and problematic
alcohol use through its association with
anhedonia.<h4>Results</h4>Analyses of data from 820
participants passing quality control procedures revealed
that the VS × ELS interaction was associated with anhedonic
symptoms (p = 0.011). Moreover, structural equation models
indirectly linked this interaction to non-anhedonic
depression symptoms and problematic alcohol use through
anhedonic symptoms and substance-related
coping.<h4>Conclusions</h4>These findings suggest that
reduced VS reactivity to reward is associated with increased
risk for anhedonia in individuals exposed to ELS. Such
stress-related anhedonia is further associated with other
depressive symptoms and problematic alcohol use through
substance-related coping.},
Doi = {10.1017/s0033291715000525},
Key = {fds251951}
}
@article{fds364221,
Author = {Nikolova, YS and Iruku, SP and Lin, C-W and Conley, ED and Puralewski,
R and French, B and Hariri, AR and Sibille, E},
Title = {FRAS1-related extracellular matrix 3 (FREM3)
single-nucleotide polymorphism effects on gene expression,
amygdala reactivity and perceptual processing speed: An
accelerated aging pathway of depression risk.},
Journal = {Frontiers in psychology},
Volume = {6},
Pages = {1377},
Year = {2015},
Month = {January},
Abstract = {The A allele of the FRAS1-related extracellular matrix
protein 3 (FREM3) rs7676614 single nucleotide polymorphism
(SNP) was linked to major depressive disorder (MDD) in an
early genome-wide association study (GWAS), and to symptoms
of psychomotor retardation in a follow-up investigation. In
line with significant overlap between age- and
depression-related molecular pathways, parallel work has
shown that FREM3 expression in postmortem human brain
decreases with age. Here, we probe the effect of rs7676614
on amygdala reactivity and perceptual processing speed, both
of which are altered in depression and aging. Amygdala
reactivity was assessed using a face-matching BOLD fMRI
paradigm in 365 Caucasian participants in the Duke
Neurogenetics Study (DNS) (192 women, mean age 19.7 ± 1.2).
Perceptual processing speed was indexed by reaction times in
the same task and the Trail Making Test (TMT). The effect of
rs7676614 on FREM3 mRNA brain expression levels was probed
in a postmortem cohort of 169 Caucasian individuals (44
women, mean age 50.8 ± 14.9). The A allele of rs7676614 was
associated with blunted amygdala reactivity to faces, slower
reaction times in the face-matching condition (p < 0.04), as
well as marginally slower performance on TMT Part B (p =
0.056). In the postmortem cohort, the T allele of rs6537170
(proxy for the rs7676614 A allele), was associated with
trend-level reductions in gene expression in Brodmann areas
11 and 47 (p = 0.066), reminiscent of patterns
characteristic of older age. The low-expressing allele of
another FREM3 SNP (rs1391187) was similarly associated with
reduced amygdala reactivity and slower TMT Part B speed, in
addition to reduced BA47 activity and extraversion (p <
0.05). Together, these results suggest common genetic
variation associated with reduced FREM3 expression may
confer risk for a subtype of depression characterized by
reduced reactivity to environmental stimuli and slower
perceptual processing speed, possibly suggestive of
accelerated aging.},
Doi = {10.3389/fpsyg.2015.01377},
Key = {fds364221}
}
@article{fds251954,
Author = {Carré, JM and Baird-Rowe, CD and Hariri, AR},
Title = {Testosterone responses to competition predict decreased
trust ratings of emotionally neutral faces.},
Journal = {Psychoneuroendocrinology},
Volume = {49},
Pages = {79-83},
Year = {2014},
Month = {November},
ISSN = {0306-4530},
Abstract = {A wealth of evidence has linked individual differences in
testosterone (T) to social, cognitive, and behavioral
processes related to human dominance. Moreover, recent
evidence indicates that a single administration of T reduces
interpersonal trust in healthy young women. Here, in a
sample of men and women (n=96), we investigated the extent
to which endogenous fluctuations in T during a competitive
interaction would predict subsequent ratings of trust from
emotionally neutral faces. Results indicated that a rise in
T predicted a decrease in trust ratings in men, but not
women. These findings provide further support for the idea
that competition-induced fluctuations in T may serve to
modulate ongoing and/or future social behavior.},
Doi = {10.1016/j.psyneuen.2014.06.011},
Key = {fds251954}
}
@article{Ahs2013,
Author = {Ahs, F and Davis, CF and Gorka, AX and Hariri, AR},
Title = {Feature-based representations of emotional facial
expressions in the human amygdala.},
Journal = {Social cognitive and affective neuroscience},
Volume = {9},
Number = {9},
Pages = {1372-1378},
Address = {Center for Cognitive Neuroscience, Duke University Box
90999, Durham, NC 27708, USA. fredrik.ahs@duke.edu.},
Year = {2014},
Month = {September},
ISSN = {1749-5016},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23887817},
Abstract = {The amygdala plays a central role in processing facial
affect, responding to diverse expressions and features
shared between expressions. Although speculation exists
regarding the nature of relationships between expression-
and feature-specific amygdala reactivity, this matter has
not been fully explored. We used functional magnetic
resonance imaging and principal component analysis (PCA) in
a sample of 300 young adults, to investigate patterns
related to expression- and feature-specific amygdala
reactivity to faces displaying neutral, fearful, angry or
surprised expressions. The PCA revealed a two-dimensional
correlation structure that distinguished emotional
categories. The first principal component separated neutral
and surprised from fearful and angry expressions, whereas
the second principal component separated neutral and angry
from fearful and surprised expressions. This two-dimensional
correlation structure of amygdala reactivity may represent
specific feature-based cues conserved across discrete
expressions. To delineate which feature-based cues
characterized this pattern, face stimuli were averaged and
then subtracted according to their principal component
loadings. The first principal component corresponded to
displacement of the eyebrows, whereas the second principal
component corresponded to increased exposure of eye whites
together with movement of the brow. Our results suggest a
convergent representation of facial affect in the amygdala
reflecting feature-based processing of discrete
expressions.},
Language = {Eng},
Doi = {10.1093/scan/nst112},
Key = {Ahs2013}
}
@article{fds251958,
Author = {Nikolova, YS and Koenen, KC and Galea, S and Wang, C-M and Seney, ML and Sibille, E and Williamson, DE and Hariri, AR},
Title = {Beyond genotype: serotonin transporter epigenetic
modification predicts human brain function.},
Journal = {Nature neuroscience},
Volume = {17},
Number = {9},
Pages = {1153-1155},
Year = {2014},
Month = {September},
ISSN = {1097-6256},
Abstract = {We examined epigenetic regulation in regards to behaviorally
and clinically relevant human brain function. Specifically,
we found that increased promoter methylation of the
serotonin transporter gene predicted increased
threat-related amygdala reactivity and decreased mRNA
expression in postmortem amygdala tissue. These patterns
were independent of functional genetic variation in the same
region. Furthermore, the association with amygdala
reactivity was replicated in a second cohort and was robust
to both sampling methods and age.},
Doi = {10.1038/nn.3778},
Key = {fds251958}
}
@article{fds251956,
Author = {Bergman, O and Åhs, F and Furmark, T and Appel, L and Linnman, C and Faria, V and Bani, M and Pich, EM and Bettica, P and Henningsson, S and Manuck, SB and Ferrell, RE and Nikolova, YS and Hariri, AR and Fredrikson, M and Westberg, L and Eriksson, E},
Title = {Association between amygdala reactivity and a dopamine
transporter gene polymorphism.},
Journal = {Translational psychiatry},
Volume = {4},
Pages = {e420},
Year = {2014},
Month = {August},
Abstract = {Essential for detection of relevant external stimuli and for
fear processing, the amygdala is under modulatory influence
of dopamine (DA). The DA transporter (DAT) is of fundamental
importance for the regulation of DA transmission by
mediating reuptake inactivation of extracellular DA. This
study examined if a common functional variable number tandem
repeat polymorphism in the 3' untranslated region of the DAT
gene (SLC6A3) influences amygdala function during the
processing of aversive emotional stimuli. Amygdala
reactivity was examined by comparing regional cerebral blood
flow, measured with positron emission tomography and
[(15)O]water, during exposure to angry and neutral faces,
respectively, in a Swedish sample comprising 32 patients
with social anxiety disorder and 17 healthy volunteers. In a
separate US sample, comprising 85 healthy volunteers studied
with blood oxygen level-dependent functional magnetic
resonance imaging, amygdala reactivity was assessed by
comparing the activity during exposure to threatening faces
and neutral geometric shapes, respectively. In both the
Swedish and the US sample, 9-repeat carriers displayed
higher amygdala reactivity than 10-repeat homozygotes. The
results suggest that this polymorphism contributes to
individual variability in amygdala reactivity.},
Doi = {10.1038/tp.2014.50},
Key = {fds251956}
}
@article{fds251957,
Author = {Goetz, SMM and Tang, L and Thomason, ME and Diamond, MP and Hariri, AR and Carré, JM},
Title = {Testosterone rapidly increases neural reactivity to threat
in healthy men: a novel two-step pharmacological challenge
paradigm.},
Journal = {Biological psychiatry},
Volume = {76},
Number = {4},
Pages = {324-331},
Year = {2014},
Month = {August},
ISSN = {0006-3223},
Abstract = {<h4>Background</h4>Previous research suggests that
testosterone (T) plays a key role in shaping competitive and
aggressive behavior in humans, possibly by modulating
threat-related neural circuitry. However, this research has
been limited by the use of T augmentation that fails to
account for baseline differences and has been conducted
exclusively in women. Thus, the extent to which normal
physiologic concentrations of T affect threat-related brain
function in men remains unknown.<h4>Methods</h4>In the
current study, we use a novel two-step pharmacologic
challenge protocol to overcome these limitations and to
evaluate causal modulation of threat- and aggression-related
neural circuits by T in healthy young men (n = 16). First,
we controlled for baseline differences in T through
administration of a gonadotropin releasing hormone
antagonist. Once a common baseline was established across
participants, we then administered T to within the normal
physiologic range. During this second step of the protocol
we acquired functional neuroimaging data to examine the
impact of T augmentation on neural circuitry supporting
threat and aggression.<h4>Results</h4>Gonadotropin releasing
hormone antagonism successfully reduced circulating
concentrations of T and brought subjects to a common
baseline. Administration of T rapidly increased circulating
T concentrations and was associated with heightened
reactivity of the amygdala, hypothalamus, and periaqueductal
grey to angry facial expressions.<h4>Conclusions</h4>These
findings provide novel causal evidence that T rapidly
potentiates the response of neural circuits mediating threat
processing and aggressive behavior in men.},
Doi = {10.1016/j.biopsych.2014.01.016},
Key = {fds251957}
}
@article{fds251959,
Author = {Carré, JM and Iselin, A-MR and Welker, KM and Hariri, AR and Dodge,
KA},
Title = {Testosterone reactivity to provocation mediates the effect
of early intervention on aggressive behavior.},
Journal = {Psychological science},
Volume = {25},
Number = {5},
Pages = {1140-1146},
Year = {2014},
Month = {May},
ISSN = {0956-7976},
Abstract = {We tested the hypotheses that the Fast Track intervention
program for high-risk children would reduce adult aggressive
behavior and that this effect would be mediated by decreased
testosterone responses to social provocation. Participants
were a subsample of males from the full trial sample, who
during kindergarten had been randomly assigned to the
10-year Fast Track intervention or to a control group. The
Fast Track program attempted to develop children's social
competencies through child social-cognitive and
emotional-coping skills training, peer-relations coaching,
academic tutoring, and classroom management, as well as
training for parents to manage their child's behavior. At a
mean age of 26 years, participants responded to laboratory
provocations. Results indicated that, relative to control
participants, men assigned to the intervention demonstrated
reduced aggression and testosterone reactivity to social
provocations. Moreover, reduced testosterone reactivity
mediated the effect of intervention on aggressive behavior,
which provides evidence for an enduring biological mechanism
underlying the effect of early psychosocial intervention on
aggressive behavior in adulthood.},
Doi = {10.1177/0956797614525642},
Key = {fds251959}
}
@article{fds303796,
Author = {Gianaros, PJ and Marsland, AL and Kuan, DC-H and Schirda, BL and Jennings, JR and Sheu, LK and Hariri, AR and Gross, JJ and Manuck,
SB},
Title = {An inflammatory pathway links atherosclerotic cardiovascular
disease risk to neural activity evoked by the cognitive
regulation of emotion.},
Journal = {Biological psychiatry},
Volume = {75},
Number = {9},
Pages = {738-745},
Year = {2014},
Month = {May},
ISSN = {0006-3223},
Abstract = {<h4>Background</h4>Cognitive reappraisal is a form of
emotion regulation that alters emotional responding by
changing the meaning of emotional stimuli. Reappraisal
engages regions of the prefrontal cortex that support
multiple functions, including visceral control functions
implicated in regulating the immune system. Immune activity
plays a role in the preclinical pathophysiology of
atherosclerotic cardiovascular disease (CVD), an
inflammatory condition that is highly comorbid with
affective disorders characterized by problems with emotion
regulation. Here, we tested whether prefrontal engagement by
reappraisal would be associated with atherosclerotic CVD
risk and whether this association would be mediated by
inflammatory activity.<h4>Methods</h4>Community volunteers
(n = 157; 30-54 years of age; 80 women) without DSM-IV
Axis-1 psychiatric diagnoses or cardiovascular or immune
disorders performed a functional neuroimaging task involving
the reappraisal of negative emotional stimuli. Carotid
artery intima-media thickness and inter-adventitial diameter
were measured by ultrasonography and used as markers of
preclinical atherosclerosis. Also measured were circulating
levels of interleukin-6 (IL-6), an inflammatory cytokine
linked to CVD risk and prefrontal neural
activity.<h4>Results</h4>Greater reappraisal-related
engagement of the dorsal anterior cingulate cortex was
associated with greater preclinical atherosclerosis and
IL-6. Moreover, IL-6 mediated the association of dorsal
anterior cingulate cortex engagement with preclinical
atherosclerosis. These results were independent of age, sex,
race, smoking status, and other known CVD risk
factors.<h4>Conclusions</h4>The cognitive regulation of
emotion might relate to CVD risk through a pathway involving
the functional interplay between the anterior cingulate
region of the prefrontal cortex and inflammatory
activity.},
Doi = {10.1016/j.biopsych.2013.10.012},
Key = {fds303796}
}
@article{fds251963,
Author = {McCarty, CA and Huggins, W and Aiello, AE and Bilder, RM and Hariri, A and Jernigan, TL and Newman, E and Sanghera, DK and Strauman, TJ and Zeng,
Y and Ramos, EM and Junkins, HA and PhenX RISING network},
Title = {PhenX RISING: real world implementation and sharing of PhenX
measures.},
Journal = {BMC Med Genomics},
Volume = {7},
Pages = {16},
Year = {2014},
Month = {March},
Abstract = {BACKGROUND: The purpose of this manuscript is to describe
the PhenX RISING network and the site experiences in the
implementation of PhenX measures into ongoing
population-based genomic studies. METHODS: Eighty PhenX
measures were implemented across the seven PhenX RISING
groups, thirty-three of which were used at more than two
sites, allowing for cross-site collaboration. Each site used
between four and 37 individual measures and five of the
sites are validating the PhenX measures through comparison
with other study measures. Self-administered and
computer-based administration modes are being evaluated at
several sites which required changes to the original PhenX
Toolkit protocols. A network-wide data use agreement was
developed to facilitate data sharing and collaboration.
RESULTS: PhenX Toolkit measures have been collected for more
than 17,000 participants across the PhenX RISING network.
The process of implementation provided information that was
used to improve the PhenX Toolkit. The Toolkit was revised
to allow researchers to select self- or interviewer
administration when creating the data collection worksheets
and ranges of specimens necessary to run biological assays
has been added to the Toolkit. CONCLUSIONS: The PhenX RISING
network has demonstrated that the PhenX Toolkit measures can
be implemented successfully in ongoing genomic studies. The
next step will be to conduct gene/environment
studies.},
Doi = {10.1186/1755-8794-7-16},
Key = {fds251963}
}
@article{fds251961,
Author = {Hyde, LW and Byrd, AL and Votruba-Drzal, E and Hariri, AR and Manuck,
SB},
Title = {Amygdala reactivity and negative emotionality: divergent
correlates of antisocial personality and psychopathy traits
in a community sample.},
Journal = {Journal of abnormal psychology},
Volume = {123},
Number = {1},
Pages = {214-224},
Year = {2014},
Month = {February},
ISSN = {0021-843X},
Abstract = {Previous studies have emphasized that antisocial personality
disorder (APD) and psychopathy overlap highly but differ
critically in several features, notably negative
emotionality (NEM) and possibly amygdala reactivity to
social signals of threat and distress. Here we examined
whether dimensions of psychopathy and APD correlate
differentially with NEM and amygdala reactivity to emotional
faces. Testing these relationships among healthy
individuals, dimensions of psychopathy and APD were
generated by the profile matching technique of Lynam and
Widiger (2001), using facet scales of the NEO Personality
Inventory-Revised, and amygdala reactivity was measured
using a well-established emotional faces task, in a
community sample of 103 men and women. Higher psychopathy
scores were associated with lower NEM and lower amygdala
reactivity, whereas higher APD scores were related to
greater NEM and greater amygdala reactivity, but only after
overlapping variance in APD and psychopathy was adjusted for
in the statistical model. Amygdala reactivity did not
mediate the relationship of APD and psychopathy scores to
NEM. Supplemental analyses also compared other measures of
factors within psychopathy in predicting NEM and amygdala
reactivity and found that Factor 2 psychopathy was
positively related to NEM and amygdala reactivity across
measures of psychopathy. The overall findings replicate
seminal observations on NEM in psychopathy by Hicks and
Patrick (2006) and extend this work to neuroimaging in a
normative population. They also suggest that one critical
way in which APD and psychopathy dimensions may differ in
their etiology is through their opposing levels of NEM and
amygdala reactivity to threat.},
Doi = {10.1037/a0035467},
Key = {fds251961}
}
@article{fds251965,
Author = {Roses, AD and Saunders, AM and Lutz, MW and Zhang, N and Hariri, AR and Asin, KE and Crenshaw, DG and Budur, K and Burns, DK and Brannan,
SK},
Title = {New applications of disease genetics and pharmacogenetics to
drug development.},
Journal = {Curr Opin Pharmacol},
Volume = {14},
Pages = {81-89},
Year = {2014},
Month = {February},
ISSN = {1471-4892},
Abstract = {TOMMORROW is a Phase III delay of onset clinical trial to
determine whether low doses of pioglitazone, a molecule that
induces mitochondrial doubling, delays the onset of MCI-AD
in normal subjects treated with low dose compared to
placebo. BOLD imaging studies in rodents and man were used
to find the dose that increases oxygen consumption at
central regions of the brain in higher proportion than
activation of large corticol regions. The trial is made
practical by the use of a pharmacogenetic algorithm based on
TOMM40 and APOE genotypes and age to identify normal
subjects at high risk of MCI-AD between the ages of 65-83
years within a five year follow-up period.},
Doi = {10.1016/j.coph.2013.12.002},
Key = {fds251965}
}
@article{fds251967,
Author = {Wellman, CL and Camp, M and Jones, VM and MacPherson, KP and Ihne, J and Fitzgerald, P and Maroun, M and Drabant, E and Bogdan, R and Hariri, AR and Holmes, A},
Title = {Corrigendum to "Convergent effects of mouse Pet-1 deletion
and human PET-1 variation on amygdala fear and threat
processing" [Exp. Neurol. 250 (2013) 260-269]},
Journal = {Experimental Neurology},
Volume = {252},
Pages = {104},
Publisher = {Elsevier BV},
Year = {2014},
Month = {February},
ISSN = {0014-4886},
Doi = {10.1016/j.expneurol.2013.11.002},
Key = {fds251967}
}
@article{fds251942,
Author = {Gorka, AX and Hanson, JL and Radtke, SR and Hariri,
AR},
Title = {Reduced hippocampal and medial prefrontal gray matter
mediate the association between reported childhood
maltreatment and trait anxiety in adulthood and predict
sensitivity to future life stress},
Journal = {Biology of Mood and Anxiety Disorders},
Volume = {4},
Number = {1},
Pages = {12-12},
Publisher = {Springer Nature},
Year = {2014},
Month = {January},
ISSN = {2045-5380},
Abstract = {Background: The experience of early life stress is a
consistently identified risk factor for the development of
mood and anxiety disorders. Preclinical research employing
animal models of early life stress has made inroads in
understanding this association and suggests that the
negative sequelae of early life stress may be mediated by
developmental disruption of corticolimbic structures
supporting stress responsiveness. Work in humans has
corroborated this idea, as childhood adversity has been
associated with alterations in gray matter volumes of the
hippocampus, amygdala, and medial prefrontal cortex. Yet,
missing from this body of research is a full understanding
of how these neurobiological vulnerabilities may
mechanistically contribute to the reported link between
adverse childhood experiences and later affective
psychopathology.Results: Analyses revealed that
self-reported childhood maltreatment was associated with
reduced gray matter volumes within the medial prefrontal
cortex and left hippocampus. Furthermore, reduced left
hippocampal and medial prefrontal gray matter volume
mediated the relationship between childhood maltreatment and
trait anxiety. Additionally, individual differences in
corticolimbic gray matter volume within these same
structures predicted the anxious symptoms as a function of
life stress 1 year after initial assessment.Conclusions:
Collectively, these findings provide novel evidence that
reductions in corticolimbic gray matter, particularly within
the hippocampus and medial prefrontal cortex, are associated
with reported childhood maltreatment and individual
differences in adult trait anxiety. Furthermore, our results
suggest that these structural alterations contribute to
increased affective sensitivity to stress later in life in
those that have experienced early adversity. More broadly,
the findings contribute to an emerging literature
highlighting the critical importance of early stress on the
development of corticolimbic structures supporting adaptive
functioning later in life.},
Doi = {10.1186/2045-5380-4-12},
Key = {fds251942}
}
@article{Lohoff2013,
Author = {Lohoff, FW and Hodge, R and Narasimhan, S and Nall, A and Ferraro, TN and Mickey, BJ and Heitzeg, MM and Langenecker, SA and Zubieta, J-K and Bogdan, R and Nikolova, YS and Drabant, E and Hariri, AR and Bevilacqua,
L and Goldman, D and Doyle, GA},
Title = {Functional genetic variants in the vesicular monoamine
transporter 1 modulate emotion processing.},
Journal = {Molecular psychiatry},
Volume = {19},
Number = {1},
Pages = {129-139},
Address = {Translational Research Laboratories, Department of
Psychiatry, Center for Neurobiology and Behavior, University
of Pennsylvania School of Medicine, Philadelphia, PA,
USA.},
Year = {2014},
Month = {January},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23337945},
Abstract = {Emotional behavior is in part heritable and often disrupted
in psychopathology. Identification of specific genetic
variants that drive this heritability may provide important
new insight into molecular and neurobiological mechanisms
involved in emotionality. Our results demonstrate that the
presynaptic vesicular monoamine transporter 1 (VMAT1)
Thr136Ile (rs1390938) polymorphism is functional in vitro,
with the Ile allele leading to increased monoamine transport
into presynaptic vesicles. Moreover, we show that the
Thr136Ile variant predicts differential responses in
emotional brain circuits consistent with its effects in
vitro. Lastly, deep sequencing of bipolar disorder (BPD)
patients and controls identified several rare novel VMAT1
variants. The variant Phe84Ser was only present in
individuals with BPD and leads to marked increase monoamine
transport in vitro. Taken together, our data show that VMAT1
polymorphisms influence monoamine signaling, the functional
response of emotional brain circuits and risk for
psychopathology.},
Language = {Eng},
Doi = {10.1038/mp.2012.193},
Key = {Lohoff2013}
}
@article{fds251964,
Author = {Goetz, SMM and Tang, L and Thomason, ME and Diamond, MP and Hariri, AR and Carré, JM},
Title = {Testosterone Rapidly Increases Neural Reactivity to Threat
in Healthy Men: A Novel Two-Step Pharmacological Challenge
Paradigm},
Journal = {Biological Psychiatry},
Volume = {76},
Number = {4},
Pages = {324-331},
Publisher = {Elsevier BV},
Year = {2014},
ISSN = {0006-3223},
Doi = {10.1016/j.biopsych.2014.01.016},
Key = {fds251964}
}
@article{Wellman2013,
Author = {Wellman, CL and Camp, M and Jones, VM and MacPherson, KP and Ihne, J and Fitzgerald, P and Maroun, M and Drabant, E and Bogdan, R and Hariri, AR and Holmes, A},
Title = {Convergent effects of mouse Pet-1 deletion and human PET-1
variation on amygdala fear and threat processing.},
Journal = {Experimental neurology},
Volume = {250},
Pages = {260-269},
Address = {Department of Psychological and Brain Sciences, Center for
the Integrative Study of Animal Behavior, Indiana
University, Bloomington, IN, USA. Electronic address:
wellmanc@indiana.edu.},
Year = {2013},
Month = {December},
ISSN = {0014-4886},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24100022},
Abstract = {Serotonin is critical for shaping the development of neural
circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain
transcription factor essential for differentiation and
forebrain targeting of serotonin neurons. Constitutive Pet-1
knockout (KO) causes major loss of serotonin neurons and
forebrain serotonin availability, and behavioral
abnormalities. We phenotyped Pet-1 KO mice for fear
conditioning and extinction, and on a battery of assays for
anxiety- and depression-related behaviors. Morphology of
Golgi-stained neurons in basolateral amygdala (BLA) and
prelimbic cortex was examined. Using human imaging genetics,
a common variant (rs860573) in the PET-1 (FEV) gene was
tested for effects on threat-related amygdala reactivity and
psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice
exhibited increased acquisition and expression of fear, and
elevated fear recovery following extinction, relative to
wild-type (WT). BLA dendrites of Pet-1 KO mice were
significantly longer than in WT. Human PET-1 variation
associated with differences in amygdala threat processing
and psychopathology. This novel evidence for the role of
Pet-1 in fear processing and dendritic organization of
amygdala neurons and in human amygdala threat processing
extends a growing literature demonstrating the influence of
genetic variation in the serotonin system on emotional
regulation via effects on structure and function of
underlying corticolimbic circuitry.},
Language = {eng},
Doi = {10.1016/j.expneurol.2013.09.025},
Key = {Wellman2013}
}
@article{fds251968,
Author = {Disner, SG and Beevers, CG and Lee, HJ and Ferrell, RE and Hariri, AR and Telch, MJ},
Title = {War zone stress interacts with the 5-HTTLPR polymorphism to
predict the development of sustained attention for negative
emotion stimuli in soldiers returning from
Iraq},
Journal = {Clinical Psychological Science},
Volume = {1},
Number = {4},
Pages = {413-425},
Publisher = {SAGE Publications},
Year = {2013},
Month = {October},
ISSN = {2167-7026},
Abstract = {Biased attention toward negative stimuli is a known
vulnerability for affective psychopathology. However,
factors that contribute to the development of this cognitive
bias are largely unknown. Variation within the serotonin
transporter gene (i.e., 5-HTTLPR) is associated with
increased susceptibility to environmental influence and
biased processing of negative stimuli. Using a passive
viewing eye-tracking paradigm, this study examined gaze
fixation for emotion stimuli in 91 U.S. Army soldiers before
and after deployment to Iraq. In addition, participants
underwent genetic assay and provided in situ measures of war
zone stress exposure. 5-HTTLPR short allele homozygotes were
more likely than other genotype groups to develop a gaze
bias toward negative stimuli as a function of increasing war
zone stress, even when controlling for postdeployment
posttraumatic stress disorder and depression severity. Short
allele homozygotes appear especially sensitive to
environmental influence, which likely contributes to the
development of cognitive vulnerability to anxiety and mood
disorders. © The Author(s) 2013.},
Doi = {10.1177/2167702613485564},
Key = {fds251968}
}
@article{Hyde2013,
Author = {Hyde, LW and Shaw, DS and Hariri, AR},
Title = {Understanding Youth Antisocial Behavior Using Neuroscience
through a Developmental Psychopathology Lens: Review,
Integration, and Directions for Research.},
Journal = {Developmental review : DR},
Volume = {33},
Number = {3},
Pages = {168-223},
Publisher = {Elsevier BV},
Address = {University of Michigan.},
Year = {2013},
Month = {September},
ISSN = {0273-2297},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24273368},
Abstract = {Youth antisocial behavior (AB) is an important public health
concern impacting perpetrators, victims, and society.
Functional neuroimaging is becoming a more common and useful
modality for understanding neural correlates of youth AB.
Although there has been a recent increase in neuroimaging
studies of youth AB and corresponding theoretical articles
on the neurobiology of AB, there has been little work
critically examining the strengths and weaknesses of
individual studies and using this knowledge to inform the
design of future studies. Additionally, research on
neuroimaging and youth AB has not been integrated within the
broader framework of developmental psychopathology. Thus,
this paper provides an in-depth review of the youth AB
functional neuroimaging literature with the following goals:
1. to evaluate how this literature has informed our
understanding of youth AB, 2. to evaluate current
neuroimaging studies of youth AB from a developmental
psychopathology perspective with a focus on integrating
research from neuroscience and developmental
psychopathology, as well as placing this research in the
context of other related areas (e.g., psychopathy, molecular
genetics), and 3. to examine strengths and weaknesses of
neuroimaging and behavioral studies of youth AB to suggest
how future studies can develop a more informed and
integrated understanding of youth AB.},
Language = {Eng},
Doi = {10.1016/j.dr.2013.06.001},
Key = {Hyde2013}
}
@article{Nikolova2013,
Author = {Nikolova, YS and Singhi, EK and Drabant, EM and Hariri,
AR},
Title = {Reward-related ventral striatum reactivity mediates
gender-specific effects of a galanin remote enhancer
haplotype on problem drinking.},
Journal = {Genes, brain, and behavior},
Volume = {12},
Number = {5},
Pages = {516-524},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience; Institute for Genome Sciences \& Policy, Duke
University, Durham, NC 27705, USA. yuliya.nikolova@duke.edu},
Year = {2013},
Month = {July},
ISSN = {1601-1848},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23489876},
Abstract = {The neuropeptide galanin has been implicated in the
regulation of appetitive and consummatory behaviors. Prior
studies have shown that direct injection of galanin into the
hypothalamus results in increased release of dopamine (DA)
in the nucleus accumbens (NAcc), and parallel increases in
food and alcohol consumption. These studies are consistent
with a role of hypothalamic galanin in regulating reward
system reactivity. In humans, a common functional haplotype
(GAL5.1) within a remote enhancer region upstream of the
galanin gene (GAL) affects promoter activity and galanin
expression in hypothalamic neurons in vitro. Given the
effects of hypothalamic galanin on NAcc DA release and the
effects of the GAL5.1 haplotype on GAL expression, we
examined the impact of this functional genetic variation on
human reward-related ventral striatum (VS) reactivity. Using
an imaging genetics strategy in Caucasian individuals
(N = 138, 72 women) participating in the ongoing Duke
Neurogenetics Study, we report a significant
gender-by-genotype interaction (right hemisphere: F1,134
= 8.08, P = 0.005; left hemisphere: F1,134
= 5.39, P = 0.022), such that homozygosity for the
GG haplotype, which predicts greater GAL expression, is
associated with relatively increased VS reactivity in women
(n = 50, right hemisphere: P = 0.015; left
hemisphere: P = 0.060), but not in men (N = 49,
P-values > 0.10). Furthermore, these differences in VS
reactivity correlated positively with differences in alcohol
use, such that VS reactivity mediated a gender-specific
association between GAL5.1 haplotype and problem drinking.
Our current results support those in animal models
implicating galanin signaling in neural pathways associated
with appetitive and consummatory behaviors of relevance for
understanding risk for substance use and
abuse.},
Language = {eng},
Doi = {10.1111/gbb.12035},
Key = {Nikolova2013}
}
@article{Zuurbier2013,
Author = {Zuurbier, LA and Nikolova, YS and Åhs, F and Hariri,
AR},
Title = {Uncinate fasciculus fractional anisotropy correlates with
typical use of reappraisal in women but not
men.},
Journal = {Emotion (Washington, D.C.)},
Volume = {13},
Number = {3},
Pages = {385-390},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience, Institute for Genome Sciences \& Policy, Duke
University, Durham, NC, USA.},
Year = {2013},
Month = {June},
ISSN = {1528-3542},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23398586},
Abstract = {Emotion regulation refers to strategies through which
individuals influence their experience and expression of
emotions. Two typical strategies are reappraisal, a
cognitive strategy for reframing the context of an emotional
experience, and suppression, a behavioral strategy for
inhibiting emotional responses. Functional neuroimaging
studies have revealed that regions of the prefrontal cortex
modulate amygdala reactivity during both strategies, but
relatively greater downregulation of the amygdala occurs
during reappraisal. Moreover, these studies demonstrated
that engagement of this modulatory circuitry varies as a
function of gender. The uncinate fasciculus is a major
structural pathway connecting regions of the anterior
temporal lobe, including the amygdala to inferior frontal
regions, especially the orbitofrontal cortex. The objective
of the current study was to map variability in the
structural integrity of the uncinate fasciculus onto
individual differences in self-reported typical use of
reappraisal and suppression. Diffusion tensor imaging was
used in 194 young adults to derive regional fractional
anisotropy values for the right and left uncinate
fasciculus. All participants also completed the Emotion
Regulation Questionnaire. In women but not men,
self-reported typical reappraisal use was positively
correlated with fractional anisotropy values in a region of
the left uncinate fasciculus within the orbitofrontal
cortex. In contrast, typical use of suppression was not
significantly correlated with fractional anisotropy in any
region of the uncinate fasciculus in either men or women.
Our data suggest that in women typical reappraisal use is
specifically related to the integrity of white matter
pathways linking the amygdala and prefrontal
cortex.},
Language = {eng},
Doi = {10.1037/a0031163},
Key = {Zuurbier2013}
}
@article{Kienast2013,
Author = {Kienast, T and Schlagenhauf, F and Rapp, MA and Wrase, J and Daig, I and Buchholz, H-G and Smolka, MN and Gründer, G and Kumakura, Y and Cumming, P and Charlet, K and Bartenstein, P and Hariri, AR and Heinz,
A},
Title = {Dopamine-modulated aversive emotion processing fails in
alcohol-dependent patients.},
Journal = {Pharmacopsychiatry},
Volume = {46},
Number = {4},
Pages = {130-136},
Address = {Department of Psychiatry and Psychotherapy, Campus Charite
Mitte, -Charite - Universitatsmedizin Berlin, Berlin,
Germany.},
Year = {2013},
Month = {June},
ISSN = {0176-3679},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23364872},
Abstract = {Negative mood states after alcohol detoxification may
enhance the relapse risk. As recently shown in healthy
volunteers, dopamine storage capacity (V d) in the left
amygdala was positively correlated with functional
activation in the left amygdala and anterior cingulate
cortex (ACC) during an emotional task; high functional
connectivity between the amygdala and the ACC, a region
important for emotion regulation, was associated with low
trait anxiety. Based on these findings, we now tested
whether detoxified alcohol-dependent patients have a
disrupted modulation of the anterior cingulate cortex
activation in response to aversive stimuli by amygdala
dopamine. Furthermore, we asked whether disrupted functional
coupling between amygdala and ACC during aversive processing
is related to trait anxiety.We used combined
6-[18F]-fluoro-l-DOPA positron emission tomography (PET),
functional magnetic resonance imaging (fMRI) and
Spielberger's state-trait anxiety questionnaire (STAI) in 11
male detoxified alcohol-dependent patients compared to 13
matched healthy controls.Unlike healthy controls, patients
showed no significant correlation between our PET metric for
dopamine storage capacity (FDOPA V d), in left amygdala and
activation in left ACC. Moreover, the functional
connectivity between amygdala and ACC during processing of
aversive emotional stimuli was reduced in patients.
Voxel-based morphometry did not reveal any discernible group
differences in amygdala volume.These results suggest that
dopamine-modulated corticolimbic circuit function is
important for responding to emotional information such that
apparent functional deficits in this neuromodulatory
circuitry may contribute to trait anxiety in
alcohol-dependent patients.},
Language = {eng},
Doi = {10.1055/s-0032-1331747},
Key = {Kienast2013}
}
@article{Prather2013,
Author = {Prather, AA and Bogdan, R and Hariri, AR},
Title = {Impact of sleep quality on amygdala reactivity, negative
affect, and perceived stress.},
Journal = {Psychosomatic medicine},
Volume = {75},
Number = {4},
Pages = {350-358},
Address = {Department of Psychiatry, University of California, San
Francisco, CA, USA. prathera@chc.ucsf.edu},
Year = {2013},
Month = {May},
ISSN = {0033-3174},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23592753},
Keywords = {Adolescent • Adult • Affect/*physiology •
Amygdala/*physiopathology • Anger •
Anxiety/physiopathology/psychology •
Depression/physiopathology/psychology • Facial
Expression • Fear • Female • Humans •
*Magnetic Resonance Imaging • Male • Self Report
• Severity of Illness Index • Sex Factors •
Sleep/*physiology • Sleep Disorders/*physiopathology/psychology
• Stress, Psychological/etiology/*physiopathology
• Visual Cortex/physiopathology • Young
Adult},
Abstract = {<h4>Objective</h4>Research demonstrates a negative impact of
sleep disturbance on mood and affect; however, the
biological mechanisms mediating these links are poorly
understood. Amygdala reactivity to negative stimuli has
emerged as one potential pathway. Here, we investigate the
influence of self-reported sleep quality on associations
between threat-related amygdala reactivity and measures of
negative affect and perceived stress.<h4>Methods</h4>Analyses
on data from 299 participants (125 men, 50.5% white, mean
[standard deviation] age = 19.6 [1.3] years) who completed
the Duke Neurogenetics Study were conducted. Participants
completed several self-report measures of negative affect
and perceived stress. Threat-related (i.e., angry and
fearful facial expressions) amygdala reactivity was assayed
using blood oxygen level-dependent functional magnetic
resonance imaging. Global sleep quality was assessed using
the Pittsburgh Sleep Quality Index.<h4>Results</h4>Amygdala
reactivity to fearful facial expressions predicted greater
depressive symptoms and higher perceived stress in poor (β
values = 0.18-1.86, p values < .05) but not good sleepers
(β values = -0.13 to -0.01, p values > .05). In
sex-specific analyses, men reporting poorer global sleep
quality showed a significant association between amygdala
reactivity and levels of depression and perceived stress (β
values = 0.29-0.44, p values < .05). In contrast, no
significant associations were observed in men reporting good
global sleep quality or in women, irrespective of sleep
quality.<h4>Conclusions</h4>This study provides novel
evidence that self-reported sleep quality moderates the
relationships between amygdala reactivity, negative affect,
and perceived stress, particularly among
men.},
Language = {eng},
Doi = {10.1097/psy.0b013e31828ef15b},
Key = {Prather2013}
}
@article{Bogdan2013,
Author = {Bogdan, R and Hyde, LW and Hariri, AR},
Title = {A neurogenetics approach to understanding individual
differences in brain, behavior, and risk for
psychopathology.},
Journal = {Molecular psychiatry},
Volume = {18},
Number = {3},
Pages = {288-299},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, Duke University, Durham, NC 27705, USA.
ryan.bogdan@duke.edu},
Year = {2013},
Month = {March},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22614291},
Abstract = {Neurogenetics research has begun to advance our
understanding of how genetic variation gives rise to
individual differences in brain function, which, in turn,
shapes behavior and risk for psychopathology. Despite these
advancements, neurogenetics research is currently confronted
by three major challenges: (1) conducting research on
individual variables with small effects, (2) absence of
detailed mechanisms, and (3) a need to translate findings
toward greater clinical relevance. In this review, we
showcase techniques and developments that address these
challenges and highlight the benefits of a neurogenetics
approach to understanding brain, behavior and
psychopathology. To address the challenge of small effects,
we explore approaches including incorporating the
environment, modeling epistatic relationships and using
multilocus profiles. To address the challenge of mechanism,
we explore how non-human animal research, epigenetics
research and genome-wide association studies can inform our
mechanistic understanding of behaviorally relevant brain
function. Finally, to address the challenge of clinical
relevance, we examine how neurogenetics research can
identify novel therapeutic targets and for whom treatments
work best. By addressing these challenges, neurogenetics
research is poised to exponentially increase our
understanding of how genetic variation interacts with the
environment to shape the brain, behavior and risk for
psychopathology.},
Language = {eng},
Doi = {10.1038/mp.2012.35},
Key = {Bogdan2013}
}
@article{fds251962,
Author = {Salazar, E and Bogdan, R and Gorka, A and Hariri, AR and Carin,
L},
Title = {Exploring the mind: Integrating questionnaires and
fMRI},
Journal = {30th International Conference on Machine Learning, ICML
2013},
Number = {PART 2},
Pages = {921-929},
Year = {2013},
Month = {January},
Abstract = {A new model is developed for joint analysis of ordered,
categorical, real and count data. The ordered and
categorical data are answers to questionnaires, the (word)
count data correspond to the text questions from the
questionnaires, and the real data correspond to fMRI
responses for each subject. The Bayesian model employs the
von Mises distribution in a novel manner to infer sparse
graphical models jointly across people, questions, fMRI
stimuli and brain region, with this integrated within a new
matrix factorization based on latent binary features. The
model is compared with simpler alternatives on two real
datasets. We also demonstrate the ability to predict the
response of the brain to visual stimuli (as measured by
fMRI), based on knowledge of how the associated person
answered classical questionnaires. Copyright 2013 by the
author(s).},
Key = {fds251962}
}
@article{Fisher2013,
Author = {Fisher, PM and Hariri, AR},
Title = {Identifying serotonergic mechanisms underlying the
corticolimbic response to threat in humans.},
Journal = {Philosophical transactions of the Royal Society of London.
Series B, Biological sciences},
Volume = {368},
Number = {1615},
Pages = {20120192},
Address = {Center for Integrated Molecular Brain Imaging, University of
Copenhagen, Copenhagen 2100, Denmark. patrick.fisher@nru.dk},
Year = {2013},
Month = {January},
ISSN = {0962-8436},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23440464},
Keywords = {Amygdala/drug effects/*metabolism/physiology •
Antidepressive Agents/pharmacology • Depression/drug
therapy/physiopathology • Fear/*physiology •
Humans • Neural Pathways/metabolism/physiology •
Neuroimaging • Personality/physiology • Prefrontal
Cortex/*metabolism/physiology • Protein Binding •
Receptor, Serotonin, 5-HT1A/metabolism •
Serotonin/*metabolism • Serotonin Uptake
Inhibitors/pharmacology},
Abstract = {A corticolimbic circuit including the amygdala and medial
prefrontal cortex (mPFC) plays an important role in
regulating sensitivity to threat, which is heightened in
mood and anxiety disorders. Serotonin is a potent
neuromodulator of this circuit; however, specific
serotonergic mechanisms mediating these effects are not
fully understood. Recent studies have evaluated molecular
mechanisms mediating the effects of serotonin signalling on
corticolimbic circuit function using a multi-modal
neuroimaging strategy incorporating positron emission
tomography and blood oxygen level-dependent functional
magnetic resonance imaging. This multi-modal neuroimaging
strategy can be integrated with additional techniques
including imaging genetics and pharmacological challenge
paradigms to more clearly understand how serotonin
signalling modulates neural pathways underlying sensitivity
to threat. Integrating these methodological approaches
offers novel opportunities to identify mechanisms through
which serotonin signalling contributes to differences in
brain function and behaviour, which in turn can illuminate
factors that confer risk for illness and inform the
development of more effective treatment strategies.},
Language = {eng},
Doi = {10.1098/rstb.2012.0192},
Key = {Fisher2013}
}
@article{Goetz2013,
Author = {Goetz, E. L. and Hariri, A. R. and Pizzagalli, D. A. and Strauman, T. J.},
Title = {Genetic moderation of the association between regulatory
focus and reward responsiveness: a proof-of-concept
study},
Journal = {Biology of mood \& anxiety disorders},
Volume = {3},
Number = {1},
Pages = {3},
Address = {Department of Psychology \& Neuroscience, Duke University,
Durham, NC, USA. elena.goetz@duke.edu.},
Year = {2013},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23369671},
Abstract = {BACKGROUND: Recent studies implicate individual differences
in regulatory focus as contributing to self-regulatory
dysfunction, particularly not responding to positive
outcomes. How such individual differences emerge, however,
is unclear. We conducted a proof-of-concept study to examine
the moderating effects of genetically driven variation in
dopamine signaling, a key modulator of neural reward
circuits, on the association between regulatory focus and
reward cue responsiveness. METHOD: Healthy Caucasians (N=59)
completed a measure of chronic regulatory focus and a
probabilistic reward task. A common functional genetic
polymorphism impacting prefrontal dopamine signaling (COMT
rs4680) was evaluated. RESULTS: Response bias, the
participants' propensity to modulate behavior as a function
of reward, was predicted by an interaction of regulatory
focus and COMT genotype. Specifically, self-perceived
success at achieving promotion goals predicted total
response bias, but only for individuals with the COMT
genotype (Val/Val) associated with relatively increased
phasic dopamine signaling and cognitive flexibility.
CONCLUSIONS: The combination of success in promotion goal
pursuit and Val/Val genotype appears to facilitate
responding to reward opportunities in the environment. This
study is among the first to integrate an assessment of
self-regulatory style with an examination of genetic
variability that underlies responsiveness to positive
outcomes in goal pursuit.},
Language = {eng},
Doi = {10.1186/2045-5380-3-3},
Key = {Goetz2013}
}
@article{Carre2013a,
Author = {Carre, J. M. and Murphy, K. R. and Hariri, A.
R.},
Title = {What lies beneath the face of aggression?},
Journal = {Social cognitive and affective neuroscience},
Volume = {8},
Number = {2},
Pages = {224--9},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, Duke University, Durham, NC, USA.
justin@carrelab.com},
Year = {2013},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22198969},
Keywords = {Adult • Aggression/*physiology •
Amygdala/*physiology • Anger/physiology •
Anthropometry • *Face/anatomy \& histology/physiology
• *Facial Expression • Fear/physiology •
Female • Humans • Magnetic Resonance
Imaging/instrumentation/*methods • Male •
Neuroimaging/methods/psychology • Neuropsychological
Tests • Sex Characteristics • Young
Adult},
Abstract = {Recent evidence indicates that a sexually dimorphic feature
of humans, the facial width-to-height ratio (FWHR), is
positively correlated with reactive aggression, particularly
in men. Also, predictions about the aggressive tendencies of
others faithfully map onto FWHR in the absence of explicit
awareness of this metric. Here, we provide the first
evidence that amygdala reactivity to social signals of
interpersonal challenge may underlie the link between
aggression and the FWHR. Specifically, amygdala reactivity
to angry faces was positively correlated with aggression,
but only among men with relatively large FWHRs. The patterns
of association were specific to angry facial expressions and
unique to men. These links may reflect the common influence
of pubertal testosterone on craniofacial growth and
development of neural circuitry underlying aggression.
Amygdala reactivity may also represent a plausible pathway
through which FWHR may have evolved to represent an honest
indicator of conspecific threat, namely by reflecting the
responsiveness of neural circuitry mediating aggressive
behavior.},
Language = {eng},
Doi = {10.1093/scan/nsr096},
Key = {Carre2013a}
}
@article{Gianaros2013,
Author = {Gianaros, PJ and Marsland, AL and Kuan, DC-H and Schirda, BL and Jennings, JR and Sheu, LK and Hariri, AR and Gross, JJ and Manuck,
SB},
Title = {An Inflammatory Pathway Links Atherosclerotic Cardiovascular
Disease Risk to Neural Activity Evoked by the Cognitive
Regulation of Emotion},
Journal = {Biological Psychiatry},
Volume = {75},
Number = {9},
Pages = {738-745},
Publisher = {Elsevier BV},
Address = {Department of Psychology (PJG, ALM, DC-HK, LKS, SBM).
Electronic address: gianaros@pitt.edu.},
Year = {2013},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24267410},
Abstract = {BACKGROUND: Cognitive reappraisal is a form of emotion
regulation that alters emotional responding by changing the
meaning of emotional stimuli. Reappraisal engages regions of
the prefrontal cortex that support multiple functions,
including visceral control functions implicated in
regulating the immune system. Immune activity plays a role
in the preclinical pathophysiology of atherosclerotic
cardiovascular disease (CVD), an inflammatory condition that
is highly comorbid with affective disorders characterized by
problems with emotion regulation. Here, we tested whether
prefrontal engagement by reappraisal would be associated
with atherosclerotic CVD risk and whether this association
would be mediated by inflammatory activity. METHODS:
Community volunteers (n = 157; 30-54 years of age; 80 women)
without DSM-IV Axis-1 psychiatric diagnoses or
cardiovascular or immune disorders performed a functional
neuroimaging task involving the reappraisal of negative
emotional stimuli. Carotid artery intima-media thickness and
inter-adventitial diameter were measured by ultrasonography
and used as markers of preclinical atherosclerosis. Also
measured were circulating levels of interleukin-6 (IL-6), an
inflammatory cytokine linked to CVD risk and prefrontal
neural activity. RESULTS: Greater reappraisal-related
engagement of the dorsal anterior cingulate cortex was
associated with greater preclinical atherosclerosis and
IL-6. Moreover, IL-6 mediated the association of dorsal
anterior cingulate cortex engagement with preclinical
atherosclerosis. These results were independent of age, sex,
race, smoking status, and other known CVD risk factors.
CONCLUSIONS: The cognitive regulation of emotion might
relate to CVD risk through a pathway involving the
functional interplay between the anterior cingulate region
of the prefrontal cortex and inflammatory
activity.},
Language = {Eng},
Doi = {10.1016/j.biopsych.2013.10.012},
Key = {Gianaros2013}
}
@article{Bogdan2012b,
Author = {Bogdan, R and Hariri, AR},
Title = {Neural embedding of stress reactivity.},
Journal = {Nature neuroscience},
Volume = {15},
Number = {12},
Pages = {1605-1607},
Year = {2012},
Month = {December},
ISSN = {1097-6256},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23187689},
Keywords = {Adolescent Behavior/*physiology • Amygdala/*growth \&
development • Anxiety/*metabolism •
Depression/*metabolism • Female • Humans •
Hydrocortisone/*metabolism • Male • Prefrontal
Cortex/*growth \& development},
Language = {eng},
Doi = {10.1038/nn.3270},
Key = {Bogdan2012b}
}
@article{White2012,
Author = {White, MG and Bogdan, R and Fisher, PM and Muñoz, KE and Williamson,
DE and Hariri, AR},
Title = {FKBP5 and emotional neglect interact to predict individual
differences in amygdala reactivity.},
Journal = {Genes, brain, and behavior},
Volume = {11},
Number = {7},
Pages = {869-878},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience, Duke University, Durham, NC,
USA.},
Year = {2012},
Month = {October},
ISSN = {1601-1848},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22979952},
Keywords = {Adolescent • Alleles • Amygdala/pathology/*physiopathology
• *Child Abuse • Female • Gene-Environment
Interaction • Haplotypes • Humans • Magnetic
Resonance Imaging • Polymorphism, Single Nucleotide
• Risk Factors • Stress, Psychological/pathology
• Tacrolimus Binding Proteins/*genetics},
Abstract = {Individual variation in physiological responsiveness to
stress mediates risk for mental illness and is influenced by
both experiential and genetic factors. Common polymorphisms
in the human gene for FK506 binding protein 5 (FKBP5), which
is involved in transcriptional regulation of the
hypothalamic-pituitary-adrenal (HPA) axis, have been shown
to interact with childhood abuse and trauma to predict
stress-related psychopathology. In the current study, we
examined if such gene-environment interaction effects may be
related to variability in the threat-related reactivity of
the amygdala, which plays a critical role in mediating
physiological and behavioral adaptations to stress including
modulation of the HPA axis. To this end, 139 healthy
Caucasian youth completed a blood oxygen level-dependent
functional magnetic resonance imaging probe of amygdala
reactivity and self-report assessments of emotional neglect
(EN) and other forms of maltreatment. These individuals were
genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780,
rs9296158, rs3800373, rs9470080 and rs9394309) previously
associated with psychopathology and/or HPA axis function.
Interactions between each SNP and EN emerged such that risk
alleles predicted relatively increased dorsal amygdala
reactivity in the context of higher EN, even after
correcting for multiple testing. Two different haplotype
analyses confirmed this relationship as haplotypes with risk
alleles also exhibited increased amygdala reactivity in the
context of higher EN. Our results suggest that increased
threat-related amygdala reactivity may represent a mechanism
linking psychopathology to interactions between common
genetic variants affecting HPA axis function and childhood
trauma.},
Language = {eng},
Doi = {10.1111/j.1601-183x.2012.00837.x},
Key = {White2012}
}
@article{Fisher2012,
Author = {Fisher, PM and Hariri, AR},
Title = {Linking variability in brain chemistry and circuit function
through multimodal human neuroimaging.},
Journal = {Genes, brain, and behavior},
Volume = {11},
Number = {6},
Pages = {633-642},
Address = {Center for Integrated Molecular Brain Imaging, Copenhagen
University Hospital Rigshospitalet, Copenhagen, Denmark.
patrick.fisher@gmail.com},
Year = {2012},
Month = {August},
ISSN = {1601-1848},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22443230},
Keywords = {Brain/physiology/radionuclide imaging • Brain
Chemistry/genetics/*physiology • Brain
Diseases/genetics/*physiopathology/*radionuclide imaging
• Humans • Magnetic Resonance Imaging/methods
• Neuroimaging/*methods • Positron-Emission
Tomography/*methods},
Abstract = {Identifying neurobiological mechanisms mediating the
emergence of individual differences in behavior is critical
for advancing our understanding of relative risk for
psychopathology. Neuroreceptor positron emission tomography
(PET) and functional magnetic resonance imaging (fMRI) can
be used to assay in vivo regional brain chemistry and
function, respectively. Typically, these neuroimaging
modalities are implemented independently despite the
capacity for integrated data sets to offer unique insight
into molecular mechanisms associated with brain function.
Through examples from the serotonin and dopamine system and
its effects on threat- and reward-related brain function, we
review evidence for how such a multimodal neuroimaging
strategy can be successfully implemented. Furthermore, we
discuss how multimodal PET-fMRI can be integrated with
techniques such as imaging genetics, pharmacological
challenge paradigms and gene-environment interaction models
to more completely map biological pathways mediating
individual differences in behavior and related risk for
psychopathology and inform the development of novel
therapeutic targets.},
Language = {eng},
Doi = {10.1111/j.1601-183x.2012.00786.x},
Key = {Fisher2012}
}
@article{Hariri2012,
Author = {Hariri, AR},
Title = {The highs and lows of amygdala reactivity in bipolar
disorders.},
Journal = {The American journal of psychiatry},
Volume = {169},
Number = {8},
Pages = {780-783},
Year = {2012},
Month = {August},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22854927},
Keywords = {Bipolar Disorder/*physiopathology •
Brain/*physiopathology • Emotions/*physiology •
Female • Humans • *Magnetic Resonance Imaging
• Male},
Language = {eng},
Doi = {10.1176/appi.ajp.2012.12050639},
Key = {Hariri2012}
}
@article{Brown2012,
Author = {Brown, AA and Jensen, J and Nikolova, YS and Djurovic, S and Agartz, I and Server, A and Ferrell, RE and Manuck, SB and Mattingsdal, M and Melle,
I and Hariri, AR and Frigessi, A and Andreassen, OA},
Title = {Genetic variants affecting the neural processing of human
facial expressions: evidence using a genome-wide functional
imaging approach.},
Journal = {Translational psychiatry},
Volume = {2},
Pages = {e143},
Address = {Division of Mental Health and Addiction, Institute of
Clinical Medicine, University of Oslo, Oslo, Norway.
andrew.brown@medisin.uio.no},
Year = {2012},
Month = {July},
ISSN = {2158-3188},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22828495},
Keywords = {Adult • Brain Mapping • *Facial Expression •
Female • Genetic Variation • Genome-Wide
Association Study • Humans • Magnetic Resonance
Imaging/methods • Male • Polymorphism, Single
Nucleotide • Reproducibility of Results • Temporal
Lobe/*physiopathology • Visual Perception/*genetics},
Abstract = {Human faces present crucial visual information for social
interaction. Specialized brain regions are involved in the
perception of faces, with the fusiform face area (FFA) a key
neuronal substrate. Face processing is genetically
controlled, but by which specific genes is unknown. A
genome-wide approach identified common single nucleotide
polymorphisms (SNPs) associated with areas of increased
brain activity in response to affective facial expressions,
measured with functional magnetic resonance imaging. SNPs in
20 genetic regions were linked with neural responses to
negative facial expressions in a Norwegian sample (n=246),
which included patients with mental illness. Three genetic
regions were linked with FFA activation in a further
discovery experiment using positive facial expressions and
involving many of the same individuals (n=284). Two of these
three regions showed significant association with right FFA
activation to negative facial expressions in an independent
North American replication sample of healthy Caucasians
(n=85, 3q26.31, P=0.004; 20p12.3, P=0.045). The activation
patterns were particularly striking for the SNP in 3q26.31,
which lies in a gene TMEM212; only the FFA was activated.
The specialized function of this brain region suggests that
TMEM212 could contribute to the innate architecture of face
processing.},
Language = {eng},
Doi = {10.1038/tp.2012.67},
Key = {Brown2012}
}
@article{Nikolova2012b,
Author = {Nikolova, YS and Bogdan, R and Brigidi, BD and Hariri,
AR},
Title = {Ventral striatum reactivity to reward and recent life stress
interact to predict positive affect.},
Journal = {Biological psychiatry},
Volume = {72},
Number = {2},
Pages = {157-163},
Address = {Department of Psychology and Neuroscience and Institute for
Genome Sciences and Policy, Duke University, Durham, NC
27705, USA. yuliya.nikolova@duke.edu},
Year = {2012},
Month = {July},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22534456},
Keywords = {Adult • Affect/*physiology • Brain
Mapping/methods/*psychology • Corpus Striatum/blood
supply/*physiology • Depressive Disorder,
Major/*physiopathology • Ethnic Groups/psychology
• Female • Humans • Life Change Events •
Magnetic Resonance Imaging/methods/psychology • Male
• *Reward • Self Report • Stress,
Psychological/*physiopathology},
Abstract = {<h4>Background</h4>Stressful life events are among the most
reliable precipitants of major depressive disorder; yet, not
everyone exposed to stress develops depression. It has been
hypothesized that robust neural reactivity to reward and
associated stable levels of positive affect (PA) may protect
against major depressive disorder in the context of
environmental adversity. However, little empirical data
exist to confirm this postulation. Here, we test the
hypothesis that individuals with relatively low ventral
striatum (VS) reactivity to reward will show low PA levels
in the context of recent life stress, while those with
relatively high VS reactivity will be protected against
these potentially depressogenic effects.<h4>Methods</h4>Differential
VS reactivity to positive feedback was assessed using blood
oxygen level-dependent functional magnetic resonance imaging
in a sample of 200 nonpatient young adults. Recent life
stress, current depressive symptoms, and PA were assessed
via self-report. Linear regression models were used to
investigate the moderating effects of VS reactivity on the
relationship between recent stress and state PA across
participants.<h4>Results</h4>Recent life stress interacted
with VS reactivity to predict self-reported state PA, such
that higher levels of life stress were associated with lower
PA for participants with relatively low, but not for those
with high, VS reactivity. These effects were independent of
age, gender, race/ethnicity, trait PA, and early childhood
trauma.<h4>Conclusions</h4>The current results provide
empirical evidence for the potentially protective role of
robust reward-related neural responsiveness against
reductions in PA that may occur in the wake of life stress
and possibly vulnerability to depression precipitated by
stressful life events.},
Language = {eng},
Doi = {10.1016/j.biopsych.2012.03.014},
Key = {Nikolova2012b}
}
@article{Sweitzer2012,
Author = {Sweitzer, MM and Donny, EC and Hariri, AR},
Title = {Imaging genetics and the neurobiological basis of individual
differences in vulnerability to addiction.},
Journal = {Drug Alcohol Depend},
Volume = {123 Suppl 1},
Number = {SUPPL.1},
Pages = {S59-S71},
Address = {Department of Psychology, University of Pittsburgh,
Pittsburgh, PA 15260, USA. mms74@pitt.edu},
Year = {2012},
Month = {June},
ISSN = {0376-8716},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22342427},
Keywords = {Adult • Basal Ganglia/drug effects • Behavior,
Addictive/*genetics/physiopathology • Genetic
Variation/*physiology • Humans • Impulsive
Behavior/*genetics/psychology • Individuality •
Male • Neural Pathways/*physiopathology •
*Neuroimaging • Phenotype • Polymorphism,
Genetic/physiology • Receptors, Dopamine
D2/*genetics/physiology • Tobacco Use
Disorder/*genetics/physiopathology},
Abstract = {BACKGROUND: Addictive disorders are heritable, but the
search for candidate functional polymorphisms playing an
etiological role in addiction is hindered by complexity of
the phenotype and the variety of factors interacting to
impact behavior. Advances in human genome sequencing and
neuroimaging technology provide an unprecedented opportunity
to explore the impact of functional genetic variants on
variability in behaviorally relevant neural circuitry. Here,
we present a model for merging these technologies to trace
the links between genes, brain, and addictive behavior.
METHODS: We describe imaging genetics and discuss the
utility of its application to addiction. We then review data
pertaining to impulsivity and reward circuitry as an example
of how genetic variation may lead to variation in behavioral
phenotype. Finally, we present preliminary data relating the
neural basis of reward processing to individual differences
in nicotine dependence. RESULTS: Complex human behaviors
such as addiction can be traced to their basic genetic
building blocks by identifying intermediate behavioral
phenotypes, associated neural circuitry, and underlying
molecular signaling pathways. Impulsivity has been linked
with variation in reward-related activation in the ventral
striatum (VS), altered dopamine signaling, and functional
polymorphisms of DRD2 and DAT1 genes. In smokers, changes in
reward-related VS activation induced by smoking abstinence
may be associated with severity of nicotine dependence.
CONCLUSIONS: Variation in genes related to dopamine
signaling may contribute to heterogeneity in VS sensitivity
to reward and, ultimately, to addiction. These findings
illustrate the utility of the imaging genetics approach for
investigating the neurobiological basis for vulnerability to
addiction.},
Language = {eng},
Doi = {10.1016/j.drugalcdep.2012.01.017},
Key = {Sweitzer2012}
}
@article{Ousdal2012,
Author = {Ousdal, OT and Anand Brown and A and Jensen, J and Nakstad, PH and Melle,
I and Agartz, I and Djurovic, S and Bogdan, R and Hariri, AR and Andreassen, OA},
Title = {Associations between variants near a monoaminergic pathways
gene (PHOX2B) and amygdala reactivity: a genome-wide
functional imaging study.},
Journal = {Twin research and human genetics : the official journal of
the International Society for Twin Studies},
Volume = {15},
Number = {3},
Pages = {273-285},
Address = {Oslo University Hospital, Oslo, Norway. o.t.ousdal@medisin.uio.no},
Year = {2012},
Month = {June},
ISSN = {1832-4274},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22856363},
Keywords = {Adult • Amygdala/*physiology • Bipolar
Disorder/genetics/physiopathology •
Catecholamines/biosynthesis • Female •
*Genome-Wide Association Study • Genotype •
Homeodomain Proteins/*genetics/metabolism • Humans
• Linkage Disequilibrium • *Magnetic Resonance
Imaging • Male • *Polymorphism, Single Nucleotide
• Schizophrenia/genetics/physiopathology •
Serotonin/biosynthesis • Signal Transduction/*genetics
• Transcription Factors/*genetics/metabolism},
Abstract = {As the amygdala is part of the phylogenetic old brain, and
its anatomical and functional properties are conserved
across species, it is reasonable to assume genetic influence
on its activity. A large corpus of candidate gene studies
indicate that individual differences in amygdala activity
may be caused by genetic variants within monoaminergic
signaling pathways such as dopamine, serotonin, and
norepinephrine. However, to our knowledge, the use of
genome-wide data to discover genetic variants underlying
individual differences in adult amygdala activity is novel.
In the present study, the combination of genome-wide data
and functional imaging phenotypes from an emotional faces
task yielded a significant association between rs10014254
and the amygdala using a region of interest approach. This
single nucleotide polymorphism is located in a regulatory
region upstream of the Paired-like homeobox 2b (PHOX2B)
gene; therefore it could affect the expression of this gene.
PHOX2B regulates the expression of enzymes necessary for the
synthesis of several monoamines and is essential for the
development of the autonomic nervous system. However, an
attempt to replicate the finding in an independent sample
from North America did not succeed. The synthesis of
functional magnetic resonance imaging (fMRI) and genome-wide
data takes a hypothesis-free approach as to which genetic
variants are of interest. Therefore, we believe that an
undirected finding within such a plausible region is of
interest, and that our results add further support to the
hypothesis that monoaminergic signaling pathways play a
central role in regulating amygdala activity.},
Language = {eng},
Doi = {10.1017/thg.2012.5},
Key = {Ousdal2012}
}
@article{Josephs2012,
Author = {Josephs, RA and Telch, MJ and Hixon, JG and Evans, JJ and Lee, H and Knopik, VS and McGeary, JE and Hariri, AR and Beevers,
CG},
Title = {Genetic and hormonal sensitivity to threat: testing a
serotonin transporter genotype × testosterone
interaction.},
Journal = {Psychoneuroendocrinology},
Volume = {37},
Number = {6},
Pages = {752-761},
Address = {Department of Psychology, The University of Texas at Austin,
Austin, TX 78756, USA. josephs@mail.psy.utexas.edu},
Year = {2012},
Month = {June},
ISSN = {0306-4530},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21978869},
Keywords = {Carbon Dioxide/diagnostic use • DNA/genetics •
Depression/genetics/psychology • Ethnic Groups •
Female • Genotype • Heterozygote • Humans
• Hydrocortisone/blood • Male • Military
Personnel • Psychiatric Status Rating Scales •
Psychomotor Performance/physiology • Questionnaires
• Saliva/chemistry • Serotonin Plasma Membrane
Transport Proteins/*genetics/*metabolism • Social
Environment • Stress, Psychological/*genetics/*metabolism
• Testosterone/*blood • Young Adult},
Abstract = {<h4>Background</h4>Striking parallels are observed when
comparing the literature on the 5-HTTLPR of the serotonin
transporter gene (SLC6A4) to the testosterone (T) literature
on measures of stress reactivity and neural activity. Short
(S) allele carriers and individuals higher in testosterone
levels show exaggerated stress responses, amygdala
hyperactivity, and reduction of amygdala-prefrontal cortex
coupling when exposed to threat.<h4>Methods</h4>Three
studies tested the hypothesis that higher T, S carriers
would show increased cortisol responses to
threat.<h4>Results</h4>Supporting the hypothesis, a T ×
5-HTTLPR interaction was obtained across all studies.
Threats to status via social exclusion (Study 1),
cognitive/perceptual failure (Study 2), and physical
competence (Study 3) all produced elevated cortisol levels
in S carriers with higher T levels. An unexpected result was
that 5-HTTLPR long (L) allele homozygotes with higher T
showed lower cortisol levels in response to threat-a pattern
of response that closely parallels that reported for
psychopathic individuals. Finally, combining effect sizes
across studies showed that the likelihood that these effects
were due to Type 1 errors was quite low.<h4>Conclusions</h4>What
emerges from these studies is a novel yet reliable, and
synergistic relationship between 5-HTTLPR genotype and
testosterone on stress reactivity, possibly conferring
vulnerability for multiple neuropsychiatric
disorders.},
Language = {eng},
Doi = {10.1016/j.psyneuen.2011.09.006},
Key = {Josephs2012}
}
@article{Bogdan2012a,
Author = {Bogdan, R and Williamson, DE and Hariri, AR},
Title = {Mineralocorticoid receptor Iso/Val (rs5522) genotype
moderates the association between previous childhood
emotional neglect and amygdala reactivity.},
Journal = {The American journal of psychiatry},
Volume = {169},
Number = {5},
Pages = {515-522},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, and Institute for Genome Sciences and Policy,
Duke University, Durham, NC, USA. bogdan.ryan@gmail.com},
Year = {2012},
Month = {May},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22407082},
Keywords = {Adolescent • Alleles • Amygdala/*physiopathology
• Child • *Child Abuse/psychology • Female
• Functional Neuroimaging • Genotype •
Homozygote • Humans • Magnetic Resonance Imaging
• Male • Mutation, Missense/*genetics/physiology
• Receptors, Mineralocorticoid/*genetics/physiology},
Abstract = {<h4>Objective</h4>The amygdala is especially reactive to
threatening stimuli, and the degree of reactivity predicts
individual differences in the expression of depression and
anxiety. Emerging research suggests that emotional neglect
during childhood as well as hypercortisolemia may lead to
heightened threat-related amygdala reactivity. This raises
the possibility that genetic variation affecting
hypothalamic-pituitary-adrenal (HPA) axis function
contributes to individual differences in amygdala
reactivity, both independently and as a function of
childhood emotional neglect.<h4>Method</h4>This study
assessed whether the mineralocorticoid receptor iso/val
polymorphism (rs5522), a functional genetic variant
affecting HPA axis function, influenced threat-related
amygdala reactivity in 279 individuals in late childhood and
early adolescence. The study also explored the extent to
which any effects of the genotype on amygdala reactivity
were contingent upon previous childhood emotional
neglect.<h4>Results</h4>Prior childhood emotional neglect
and the val allele were associated with greater amygdala
reactivity. Moreover, a significant genotype-by-emotional
neglect interaction was observed whereby greater amygdala
reactivity in val allele carriers was independent of
previous childhood emotional neglect, while greater
reactivity in iso homozygotes was revealed only in the
context of a history of elevated emotional neglect. At
relatively low levels of previous emotional neglect, val
carriers had heightened amygdala reactivity relative to iso
homozygotes.<h4>Conclusions</h4>These results suggest that
relatively greater amygdala reactivity may represent a
biological mechanism through which childhood adversity and
functional genetic variation in HPA axis responsiveness to
stress may mediate risk for psychopathology.},
Language = {eng},
Doi = {10.1176/appi.ajp.2011.11060855},
Key = {Bogdan2012a}
}
@article{Lahey2012a,
Author = {Lahey, BB and McNealy, K and Knodt, A and Zald, DH and Sporns, O and Manuck, SB and Flory, JD and Applegate, B and Rathouz, PJ and Hariri,
AR},
Title = {Using confirmatory factor analysis to measure
contemporaneous activation of defined neuronal networks in
functional magnetic resonance imaging.},
Journal = {NeuroImage},
Volume = {60},
Number = {4},
Pages = {1982-1991},
Address = {Department of Health Studies, University of Chicago,
Chicago, IL 60637, United States. blahey@health.bsd.uchicago.edu},
Year = {2012},
Month = {May},
ISSN = {1053-8119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22348884},
Keywords = {Adolescent • Adult • Brain/physiology • Brain
Mapping/*methods • *Factor Analysis, Statistical •
Female • Humans • Image Interpretation,
Computer-Assisted/*methods • *Magnetic Resonance
Imaging • Male • *Models, Theoretical • Young
Adult},
Abstract = {Functional neuroimaging often generates large amounts of
data on regions of interest. Such data can be addressed
effectively with a widely-used statistical technique based
on measurement theory that has not yet been applied to
neuroimaging. Confirmatory factor analysis is a convenient
hypothesis-driven modeling environment that can be used to
conduct formal statistical tests comparing alternative
hypotheses regarding the elements of putative neuronal
networks. In such models, measures of each activated region
of interest are treated as indicators of an underlying
latent construct that represents the contemporaneous
activation of the elements in the network. As such,
confirmatory factor analysis focuses analyses on the
activation of hypothesized networks as a whole, improves
statistical power by modeling measurement error, and
provides a theory-based approach to data reduction with a
robust statistical basis. This approach is illustrated using
data on seven regions of interest in a hypothesized
mesocorticostriatal reward system in a sample of 262 adult
volunteers assessed during a card-guessing reward task. A
latent construct reflecting contemporaneous activation of
the reward system was found to be significantly associated
with a latent construct measuring impulsivity, particularly
in males.},
Language = {eng},
Doi = {10.1016/j.neuroimage.2012.02.002},
Key = {Lahey2012a}
}
@article{Terburg2012,
Author = {Terburg, D and Morgan, BE and Montoya, ER and Hooge, IT and Thornton,
HB and Hariri, AR and Panksepp, J and Stein, DJ and van Honk,
J},
Title = {Hypervigilance for fear after basolateral amygdala damage in
humans.},
Journal = {Translational psychiatry},
Volume = {2},
Pages = {e115},
Address = {Department of Psychology, Utrecht University, Utrecht, The
Netherlands. d.terburg@uu.nl},
Year = {2012},
Month = {May},
ISSN = {2158-3188},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22832959},
Keywords = {Adult • Amygdala/*physiopathology •
Anxiety/genetics/pathology/*physiopathology • Attention
• Brain Damage, Chronic/genetics/pathology/*physiopathology
• Brain Mapping • Calcinosis/genetics/pathology/physiopathology
• Discrimination (Psychology)/physiology •
Dominance, Cerebral/physiology • Emotions/physiology
• Facial Expression • Fear/*physiology •
Female • Humans • Image Interpretation,
Computer-Assisted • Lipoid Proteinosis of Urbach and
Wiethe/genetics/pathology/*physiopathology • Magnetic
Resonance Imaging • Male • Middle Aged •
Nerve Growth Factors • Neural Inhibition/*physiology
• Pattern Recognition, Visual/physiology •
Recognition (Psychology)/physiology • Reference Values
• Stroop Test • Subliminal Stimulation},
Abstract = {Recent rodent research has shown that the basolateral
amygdala (BLA) inhibits unconditioned, or innate, fear. It
is, however, unknown whether the BLA acts in similar ways in
humans. In a group of five subjects with a rare genetic
syndrome, that is, Urbach-Wiethe disease (UWD), we used a
combination of structural and functional neuroimaging, and
established focal, bilateral BLA damage, while other
amygdala sub-regions are functionally intact. We tested the
translational hypothesis that these BLA-damaged UWD-subjects
are hypervigilant to facial expressions of fear, which are
prototypical innate threat cues in humans. Our data indeed
repeatedly confirm fear hypervigilance in these UWD
subjects. They show hypervigilant responses to unconsciously
presented fearful faces in a modified Stroop task. They
attend longer to the eyes of dynamically displayed fearful
faces in an eye-tracked emotion recognition task, and in
that task recognize facial fear significantly better than
control subjects. These findings provide the first direct
evidence in humans in support of an inhibitory function of
the BLA on the brain's threat vigilance system, which has
important implications for the understanding of the
amygdala's role in the disorders of fear and
anxiety.},
Language = {eng},
Doi = {10.1038/tp.2012.46},
Key = {Terburg2012}
}
@article{Joeyen-Waldorf2012,
Author = {Joeyen-Waldorf, J and Nikolova, YS and Edgar, N and Walsh, C and Kota,
R and Lewis, DA and Ferrell, R and Manuck, SB and Hariri, AR and Sibille,
E},
Title = {Adenylate cyclase 7 is implicated in the biology of
depression and modulation of affective neural
circuitry.},
Journal = {Biological psychiatry},
Volume = {71},
Number = {7},
Pages = {627-632},
Address = {Department of Psychiatry, University of Pittsburgh,
Pennsylvania 15219, USA.},
Year = {2012},
Month = {April},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22264442},
Keywords = {Adenylate Cyclase/genetics/metabolism/*physiology •
Adult • Amygdala/metabolism/*physiopathology •
Animals • Depressive Disorder/genetics/metabolism/*physiopathology
• Disease Models, Animal • Emotions/*physiology
• Female • Functional Neuroimaging/methods/*psychology
• Gene Expression/genetics/physiology • Genetic
Predisposition to Disease • Genotype • Gyrus
Cinguli/physiopathology • Humans • Magnetic
Resonance Imaging/methods/psychology • Male • Mice
• Mice, Inbred C57BL • Mice, Knockout •
Polymorphism, Single Nucleotide • Serotonin Plasma
Membrane Transport Proteins/genetics},
Abstract = {<h4>Background</h4>Evolutionarily conserved genes and their
associated molecular pathways can serve as a translational
bridge between human and mouse research, extending our
understanding of biological pathways mediating individual
differences in behavior and risk for psychopathology.<h4>Methods</h4>Comparative
gene array analysis in the amygdala and cingulate cortex
between the serotonin transporter knockout mouse, a genetic
animal model replicating features of human depression, and
existing brain transcriptome data from postmortem tissue
derived from clinically depressed humans was conducted to
identify genes with similar changes across species (i.e.,
conserved) that may help explain risk of depressive-like
phenotypes. Human neuroimaging analysis was then used to
investigate the impact of a common single-nucleotide
polymorphism (rs1064448) in a gene with identified conserved
human-mouse changes, adenylate cyclase 7 (ADCY7), on
threat-associated amygdala reactivity in two large
independent samples.<h4>Results</h4>Comparative analysis
identified genes with conserved transcript changes in
amygdala (n = 29) and cingulate cortex (n = 19), both
critically involved in the generation and regulation of
emotion. Selected results were confirmed by real-time
quantitative polymerase chain reaction, including
upregulation in the amygdala of transcripts for ADCY7, a
gene previously implicated in human depression and
associated with altered emotional responsiveness in mouse
models. Translating these results back to living healthy
human subjects, we show that genetic variation (rs1064448)
in ADCY7 biases threat-related amygdala reactivity.<h4>Conclusions</h4>This
converging cross-species evidence implicates ADCY7 in the
modulation of mood regulatory neural mechanisms and,
possibly, risk for and pathophysiology of depression,
together supporting a continuous dimensional approach to
major depressive disorder and other affective
disorders.},
Language = {eng},
Doi = {10.1016/j.biopsych.2011.11.029},
Key = {Joeyen-Waldorf2012}
}
@article{Drabant2012,
Author = {Drabant, EM and Ramel, W and Edge, MD and Hyde, LW and Kuo, JR and Goldin,
PR and Hariri, AR and Gross, JJ},
Title = {Neural mechanisms underlying 5-HTTLPR-related sensitivity to
acute stress.},
Journal = {The American journal of psychiatry},
Volume = {169},
Number = {4},
Pages = {397-405},
Address = {Department of Psychology, Stanford University, Stanford,
California, USA.},
Year = {2012},
Month = {April},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22362395},
Keywords = {Adult • Alleles • Brain/*physiopathology •
Female • Functional Neuroimaging/methods/*psychology
• Genotype • Humans • Magnetic Resonance
Imaging/methods/*psychology • Neural
Pathways/physiopathology • Polymorphism, Single
Nucleotide • Serotonin Plasma Membrane Transport
Proteins/genetics/*physiology • Stress,
Psychological/genetics/*physiopathology},
Abstract = {<h4>Objective</h4>Many studies have shown that 5-HTTLPR
genotype interacts with exposure to stress in conferring
risk for psychopathology. However, the specific neural
mechanisms through which this gene-by-environment
interaction confers risk remain largely unknown, and no
study to date has directly examined the modulatory effects
of 5-HTTLPR on corticolimbic circuit responses during
exposure to acute stress.<h4>Method</h4>An acute laboratory
stressor was administered to 51 healthy women during
blood-oxygen-level-dependent functional magnetic resonance
imaging. In this task, participants were threatened with
electric shocks of uncertain intensity, which were
unpredictably delivered to the wrist after a long
anticipatory cue period of unpredictable
duration.<h4>Results</h4>Relative to women carrying the L
allele, those with the SS genotype showed enhanced
activation during threat anticipation in a network of
regions, including the amygdala, hippocampus, anterior
insula, thalamus, pulvinar, caudate, precuneus, anterior
cingulate cortex, and medial prefrontal cortex. Individuals
with the SS genotype also displayed enhanced positive
coupling between medial prefrontal cortex activation and
anxiety experience, whereas enhanced negative coupling
between insula activation and perceived success at
regulating anxiety was observed in individuals carrying the
L allele.<h4>Conclusions</h4>These findings suggest that
during stress exposure, neural systems that enhance fear and
arousal, modulate attention toward threat, and perseverate
on emotional salience of the threat may be engaged
preferentially in individuals with the SS genotype. This may
be one mechanism underlying the risk for psychopathology
conferred by the S allele upon exposure to life
stressors.},
Language = {eng},
Doi = {10.1176/appi.ajp.2011.10111699},
Key = {Drabant2012}
}
@article{Carre2012,
Author = {Carré, JM and Fisher, PM and Manuck, SB and Hariri,
AR},
Title = {Interaction between trait anxiety and trait anger predict
amygdala reactivity to angry facial expressions in men but
not women.},
Journal = {Social cognitive and affective neuroscience},
Volume = {7},
Number = {2},
Pages = {213-221},
Address = {Department of Psychology and Neuroscience, Duke University,
Durham, NC 27708, USA. justin.carre@duke.edu},
Year = {2012},
Month = {February},
ISSN = {1749-5016},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21183456},
Keywords = {Adult • Amygdala/*physiology • Anger/*physiology
• Anxiety/*psychology • Brain/physiology •
Emotions/physiology • *Facial Expression • Female
• Humans • Individuality • Male • Middle
Aged • Neuroimaging},
Abstract = {The amygdala is critically involved in mediating
physiological and behavioral responses to threat. In
particular, neuroimaging research indicates that the
amygdala is highly responsive to facial signals of threat
such as fearful and angry expressions. However, individuals
differ substantially in both their relative sensitivity to
threat and the magnitude of amygdala reactivity to facial
signals of threat. Here, we report the novel finding that
individual differences in trait anger are positively
correlated with bilateral dorsal amygdala reactivity to
angry facial expressions, but only among men with elevated
trait anxiety scores. These findings add to the growing body
of evidence indicating that variability in personality
traits contribute to individual differences in
threat-related amygdala reactivity and further suggest that
heightened amygdala reactivity to angry faces may be
uniquely involved in the expression of reactive aggression
in men.},
Language = {eng},
Doi = {10.1093/scan/nsq101},
Key = {Carre2012}
}
@article{Davis2013,
Author = {Davis, FC and Knodt, AR and Sporns, O and Lahey, BB and Zald, DH and Brigidi, BD and Hariri, AR},
Title = {Impulsivity and the Modular Organization of Resting-State
Neural Networks},
Journal = {Cerebral cortex},
Volume = {23},
Number = {6},
Pages = {1444-1452},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, Duke University, Durham, NC 27708, USA.
caroline.davis@duke.edu},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22645253},
Keywords = {Adolescent • *Brain Mapping • Female • Head
Movements • Humans • Image Processing,
Computer-Assisted • Impulsive Behavior/classification/*pathology
• Magnetic Resonance Imaging • Male • Models,
Neurological • Neural Pathways/blood supply/*pathology
• Oxygen • Rest/*physiology • Self Report
• Young Adult},
Abstract = {Impulsivity is a complex trait associated with a range of
maladaptive behaviors, including many forms of
psychopathology. Previous research has implicated multiple
neural circuits and neurotransmitter systems in impulsive
behavior, but the relationship between impulsivity and
organization of whole-brain networks has not yet been
explored. Using graph theory analyses, we characterized the
relationship between impulsivity and the functional
segregation (``modularity'') of the whole-brain network
architecture derived from resting-state functional magnetic
resonance imaging (fMRI) data. These analyses revealed
remarkable differences in network organization across the
impulsivity spectrum. Specifically, in highly impulsive
individuals, regulatory structures including medial and
lateral regions of the prefrontal cortex were isolated from
subcortical structures associated with appetitive drive,
whereas these brain areas clustered together within the same
module in less impulsive individuals. Further exploration of
the modular organization of whole-brain networks revealed
novel shifts in the functional connectivity between visual,
sensorimotor, cortical, and subcortical structures across
the impulsivity spectrum. The current findings highlight the
utility of graph theory analyses of resting-state fMRI data
in furthering our understanding of the neurobiological
architecture of complex behaviors.},
Language = {eng},
Doi = {10.1093/cercor/bhs126},
Key = {Davis2013}
}
@article{Bogdan2012c,
Author = {Bogdan, R and Carre, JM and Hariri, AR},
Title = {Toward a mechanistic understanding of how variability in
neurobiology shapes individual differences in
behavior},
Journal = {Current topics in behavioral neurosciences},
Volume = {12},
Pages = {361-393},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience, Institute for Genome Sciences \& Policy, Duke
University, 417 Chapel Drive, Durham, NC, 27708, USA,
bogdan.ryan@gmail.com.},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22437943},
Abstract = {Research has begun to identify how variability in brain
function contributes to individual differences in complex
behavioral traits. Examining variability in molecular
signaling pathways with emerging and established
methodologies such as pharmacologic fMRI, multimodal
PET/fMRI, and hormonal assays are beginning to provide a
mechanistic understanding of how individual differences in
brain function arise. Against this background, functional
genetic polymorphisms are being utilized to understand the
origins of variability in signaling pathways as well as to
efficiently model how such emergent variability impacts
behaviorally relevant brain function and health outcomes.
This chapter provides an overview of a research strategy
that integrates these complimentary levels of analysis;
existing empirical data is used to illustrate the
effectiveness of this approach in illuminating the
mechanistic neurobiology of individual differences in
complex behavioral traits. This chapter also discusses how
such efforts can contribute to the identification of
predictive risk markers that interact with unique
environmental factors to precipitate psychopathology.},
Language = {eng},
Doi = {10.1007/7854_2011_182},
Key = {Bogdan2012c}
}
@article{Minkel2012,
Author = {Minkel, JD and McNealy, K and Gianaros, PJ and Drabant, EM and Gross,
JJ and Manuck, SB and Hariri, AR},
Title = {Sleep quality and neural circuit function supporting emotion
regulation},
Journal = {Biology of mood \& anxiety disorders},
Volume = {2},
Number = {1},
Pages = {22},
Publisher = {Springer Science and Business Media LLC},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience, Duke University, 417 Chapel Dr,, Durham, NC
27708, USA. jared.minkel@duke.edu.},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23216889},
Abstract = {ABSTRACT: BACKGROUND: Recent laboratory studies employing an
extended sleep deprivation model have mapped sleep-related
changes in behavior onto functional alterations in specific
brain regions supporting emotion, suggesting possible
biological mechanisms for an association between sleep
difficulties and deficits in emotion regulation. However, it
is not yet known if similar behavioral and neural changes
are associated with the more modest variability in sleep
observed in daily life. METHODS: We examined relationships
between sleep and neural circuitry of emotion using the
Pittsburgh Sleep Quality Index and fMRI data from a widely
used emotion regulation task focusing on cognitive
reappraisal of negative emotional stimuli in an unselected
sample of 97 adult volunteers (48 women; mean age
42.78+/-7.37years, range 30--54years old). RESULTS: Emotion
regulation was associated with greater activation in
clusters located in the dorsomedial prefrontal cortex
(dmPFC), left dorsolateral prefrontal cortex (dlPFC), and
inferior parietal cortex. Only one subscale from the
Pittsburgh Sleep Quality Index, use of sleep medications,
was related to BOLD responses in the dmPFC and dlPFC during
cognitive reappraisal. Use of sleep medications predicted
lesser BOLD responses during reappraisal, but other aspects
of sleep, including sleep duration and subjective sleep
quality, were not related to neural activation in this
paradigm. CONCLUSIONS: The relatively modest variability in
sleep that is common in the general community is unlikely to
cause significant disruption in neural circuits supporting
reactivity or regulation by cognitive reappraisal of
negative emotion. Use of sleep medication however, may
influence emotion regulation circuitry, but additional
studies are necessary to determine if such use plays a
causal role in altering emotional responses.},
Language = {eng},
Doi = {10.1186/2045-5380-2-22},
Key = {Minkel2012}
}
@article{Carre2013b,
Author = {Carre, JM and Hyde, LW and Neumann, CS and Viding, E and Hariri,
AR},
Title = {The neural signatures of distinct psychopathic
traits},
Journal = {Social neuroscience},
Volume = {8},
Number = {2},
Pages = {122-135},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, Duke University, Durham, NC, USA.
justin.carre@wayne.edu},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22775289},
Keywords = {Amygdala/pathology • Antisocial Personality
Disorder/pathology/psychology • Data Interpretation,
Statistical • Female • Humans • Image
Processing, Computer-Assisted • Impulsive
Behavior/pathology/psychology • Magnetic Resonance
Imaging • Male • Neostriatum/pathology •
Nervous System/*pathology • Neuropsychological Tests
• Oxygen/blood • Reward • Sex Characteristics
• Young Adult},
Abstract = {Recent studies suggest that psychopathy may be associated
with dysfunction in the neural circuitry supporting both
threat- and reward-related processes. However, these studies
have involved small samples and often focused on extreme
groups. Thus, it is unclear to what extent current findings
may generalize to psychopathic traits in the general
population. Furthermore, no studies have systematically and
simultaneously assessed associations between distinct
psychopathy facets and both threat- and reward-related brain
function in the same sample of participants. Here, we
examined the relationship between threat-related amygdala
reactivity and reward-related ventral striatum (VS)
reactivity and variation in four facets of self-reported
psychopathy in a sample of 200 young adults. Path models
indicated that amygdala reactivity to fearful facial
expressions is negatively associated with the interpersonal
facet of psychopathy, whereas amygdala reactivity to angry
facial expressions is positively associated with the
lifestyle facet. Furthermore, these models revealed that
differential VS reactivity to positive versus negative
feedback is negatively associated with the lifestyle facet.
There was suggestive evidence for gender-specific patterns
of association between brain function and psychopathy
facets. Our findings are the first to document differential
associations between both threat- and reward-related neural
processes and distinct facets of psychopathy and thus
provide a more comprehensive picture of the pattern of
neural vulnerabilities that may predispose to maladaptive
outcomes associated with psychopathy.},
Language = {eng},
Doi = {10.1080/17470919.2012.703623},
Key = {Carre2013b}
}
@article{Nikolova2012a,
Author = {Nikolova, YS and Hariri, AR},
Title = {Neural responses to threat and reward interact to predict
stress-related problem drinking: A novel protective role of
the amygdala},
Journal = {Biology of mood \& anxiety disorders},
Volume = {2},
Number = {1},
Pages = {19},
Publisher = {Springer Science and Business Media LLC},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience and Institute for Genome Sciences \& Policy,
Duke University, NC 27708, Durham, USA. yuliya.nikolova@duke.edu.},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23151390},
Abstract = {ABSTRACT: BACKGROUND: Research into neural mechanisms of
drug abuse risk has focused on the role of dysfunction in
neural circuits for reward. In contrast, few studies have
examined the role of dysfunction in neural circuits of
threat in mediating drug abuse risk. Although typically
regarded as a risk factor for mood and anxiety disorders,
threat-related amygdala reactivity may serve as a protective
factor against substance use disorders, particularly in
individuals with exaggerated responsiveness to reward.
FINDINGS: We used well-established neuroimaging paradigms to
probe threat-related amygdala and reward-related ventral
striatum reactivity in a sample of 200 young adult students
from the ongoing Duke Neurogenetics Study. Recent life
stress and problem drinking were assessed using self-report.
We found a significant three-way interaction between
threat-related amygdala reactivity, reward-related ventral
striatum reactivity, and recent stress, wherein individuals
with higher reward-related ventral striatum reactivity
exhibit higher levels of problem drinking in the context of
stress, but only if they also have lower threat-related
amygdala reactivity. This three-way interaction predicted
both contemporaneous problem drinking and problem drinking
reported three-months later in a subset of participants.
CONCLUSIONS: These findings suggest complex interactions
between stress and neural responsiveness to both threat and
reward mediate problem drinking. Furthermore, they highlight
a novel protective role for threat-related amygdala
reactivity against drug use in individuals with high neural
reactivity to reward.},
Language = {eng},
Doi = {10.1186/2045-5380-2-19},
Key = {Nikolova2012a}
}
@article{Gunduz-Cinar2013,
Author = {Gunduz Cinar and O and Macpherson, KP and Cinar, R and Gamble George and J and Sugden, K and Williams, B and Godlewski, G and Ramikie, TS and Gorka,
AX and Alapafuja, SO and Nikas, SP and Makriyannis, A and Poulton, R and Patel, S and Hariri, AR and Caspi, A and Moffitt, TE and Kunos, G and Holmes, A},
Title = {Convergent translational evidence of a role for anandamide
in amygdala-mediated fear extinction, threat processing and
stress-reactivity},
Journal = {Molecular psychiatry},
Volume = {18},
Number = {7},
Pages = {813-823},
Address = {Laboratory of Behavioral and Genomic Neuroscience, Section
on Behavioral and Genomic Neuroscience, National Institute
on Alcoholism and Alcohol Abuse, NIH, Bethesda, MD,
USA.},
Year = {2012},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22688188},
Abstract = {Endocannabinoids are released 'on-demand' on the basis of
physiological need, and can be pharmacologically augmented
by inhibiting their catabolic degradation. The
endocannabinoid anandamide is degraded by the catabolic
enzyme fatty acid amide hydrolase (FAAH). Anandamide is
implicated in the mediation of fear behaviors, including
fear extinction, suggesting that selectively elevating brain
anandamide could modulate plastic changes in fear. Here we
first tested this hypothesis with preclinical experiments
employing a novel, potent and selective FAAH inhibitor,
AM3506 (5-(4-hydroxyphenyl)pentanesulfonyl fluoride).
Systemic AM3506 administration before extinction decreased
fear during a retrieval test in a mouse model of impaired
extinction. AM3506 had no effects on fear in the absence of
extinction training, or on various non-fear-related
measures. Anandamide levels in the basolateral amygdala were
increased by extinction training and augmented by systemic
AM3506, whereas application of AM3506 to amygdala slices
promoted long-term depression of inhibitory transmission, a
form of synaptic plasticity linked to extinction. Further
supporting the amygdala as effect-locus, the fear-reducing
effects of systemic AM3506 were blocked by intra-amygdala
infusion of a CB1 receptor antagonist and were fully
recapitulated by intra-amygdala infusion of AM3506. On the
basis of these preclinical findings, we hypothesized that
variation in the human FAAH gene would predict individual
differences in amygdala threat-processing and stress-coping
traits. Consistent with this, carriers of a low-expressing
FAAH variant (385A allele; rs324420) exhibited quicker
habituation of amygdala reactivity to threat, and had lower
scores on the personality trait of stress-reactivity. Our
findings show that augmenting amygdala anandamide enables
extinction-driven reductions in fear in mouse and may
promote stress-coping in humans.Molecular Psychiatry advance
online publication, 12 June 2012; doi:10.1038/mp.2012.72.},
Language = {eng},
Doi = {10.1038/mp.2012.72},
Key = {Gunduz-Cinar2013}
}
@article{Lahey2012b,
Author = {Lahey, BB and Applegate, B and Hakes, JK and Zald, DH and Hariri, AR and Rathouz, PJ},
Title = {Is there a general factor of prevalent psychopathology
during adulthood?},
Journal = {Journal of abnormal psychology},
Volume = {121},
Number = {4},
Pages = {971-977},
Address = {Department of Health Studies (MC 2007), University of
Chicago, Chicago, IL 60637, USA. blahey@uchicago.edu},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22845652},
Keywords = {Adolescent • Adult • Comorbidity • Diagnostic
and Statistical Manual of Mental Disorders • Factor
Analysis, Statistical • Female • Humans •
Interview, Psychological • Male • Mental
Disorders/diagnosis/*epidemiology • Middle Aged •
*Models, Psychological • Prevalence},
Abstract = {The patterns of comorbidity among prevalent mental disorders
in adults lead them to load on ``externalizing,''
``distress,'' and ``fears'' factors. These factors are
themselves robustly correlated, but little attention has
been paid to this fact. As a first step in studying the
implications of these interfactor correlations, we conducted
confirmatory factor analyses on diagnoses of 11 prevalent
Diagnostic and Statistical Manual of Mental Disorders (4th
ed.) mental disorders in a nationally representative sample.
A model specifying correlated externalizing, distress, and
fears factors fit well, but an alternative model was tested
in which a ``general'' bifactor was added to capture what
these disorders share in common. There was a modest but
significant improvement in fit for the bifactor model
relative to the 3-factor oblique model, with all disorders
loading strongly on the bifactor. Tests of external validity
revealed that the fears, distress, and externalizing factors
were differentially associated with measures of functioning
and potential risk factors. Nonetheless, the general
bifactor accounted for significant independent variance in
future psychopathology, functioning, and other criteria over
and above the fears, distress, and externalizing factors.
These findings support the hypothesis that these prevalent
forms of psychopathology have both important common and
unique features. Future studies should determine whether
this is because they share elements of their etiology and
neurobiological mechanisms. If so, the existence of common
features across diverse forms of prevalent psychopathology
could have important implications for understanding the
nature, etiology, and outcomes of psychopathology. (PsycINFO
Database Record (c) 2012 APA, all rights
reserved).},
Language = {eng},
Doi = {10.1037/a0028355},
Key = {Lahey2012b}
}
@article{Hyde2011b,
Author = {Hyde, LW and Bogdan, R and Hariri, AR},
Title = {Understanding risk for psychopathology through imaging
gene-environment interactions.},
Journal = {Trends in cognitive sciences},
Volume = {15},
Number = {9},
Pages = {417-427},
Address = {Department of Psychology and Center for the Neural Basis of
Cognition, University of Pittsburgh, 210 South Bouquet St,
Pittsburgh, PA 15260, USA. LWH2@pitt.edu},
Year = {2011},
Month = {September},
ISSN = {1364-6613},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21839667},
Keywords = {Brain/*pathology/physiopathology • Epigenomics •
*Gene-Environment Interaction • *Genetic Predisposition
to Disease • Humans • Models, Biological •
Neuroimaging • *Psychopathology},
Abstract = {Examining the interplay of genes, experience and the brain
is crucial to understanding psychopathology. We review the
recent gene-environment interaction (G×E) and imaging
genetics literature with the goal of developing models to
bridge these approaches within single imaging
gene-environment interaction (IG×E) studies. We explore
challenges inherent in both G×E and imaging genetics and
highlight studies that address these limitations. In
specifying IG×E models, we examine statistical methods for
combining these approaches, and explore plausible biological
mechanisms (e.g. epigenetics) through which these
conditional mechanisms can be understood. Finally, we
discuss the potential contribution that IG×E studies can
make to understanding psychopathology and developing more
personalized and effective prevention and
treatment.},
Language = {eng},
Doi = {10.1016/j.tics.2011.07.001},
Key = {Hyde2011b}
}
@article{Nikolova2011,
Author = {Nikolova, YS and Ferrell, RE and Manuck, SB and Hariri,
AR},
Title = {Multilocus genetic profile for dopamine signaling predicts
ventral striatum reactivity.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {36},
Number = {9},
Pages = {1940-1947},
Address = {Department of Psychology and Neuroscience, Duke University,
Durham, NC, USA.},
Year = {2011},
Month = {August},
ISSN = {0893-133X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21593733},
Keywords = {Adult • Basal Ganglia/*metabolism/physiopathology
• Cohort Studies • Dopamine/genetics/*physiology
• Dopamine Plasma Membrane Transport Proteins/genetics
• Female • Gene Expression Profiling/*methods
• Genetic Loci/*genetics • Genetic Predisposition
to Disease/genetics • Humans • Male • Middle
Aged • Mood Disorders/diagnosis/*genetics/physiopathology
• Polymorphism, Genetic/genetics • Predictive
Value of Tests • Receptors, Dopamine D2/genetics •
Receptors, Dopamine D4/genetics • Signal
Transduction/*genetics},
Abstract = {Research integrating neuroimaging and molecular genetics has
yielded important insights into how variability in brain
chemistry predicts individual differences in brain function,
behavior and related risk for psychopathology. However,
existing studies have been limited by their focus on the
independent effects of single polymorphisms with modest
impact on brain chemistry. Here, we explored the effects of
five functional polymorphisms affecting dopamine (DA)
signaling on reward-related ventral striatum (VS)
reactivity, measured with BOLD fMRI, in a sample of 69
Caucasians. We also compiled individual multilocus genetic
profile scores reflecting the additive effects of alleles
conferring relatively increased DA signaling across the five
polymorphic loci: DAT1 9-repeat, DRD4 7-repeat, DRD2 -141C
Del, DRD2 Taq1A C (A2), and COMT (158)Met. These multilocus
DA profile scores accounted for 10.9% of the
inter-individual variability in reward-related VS
reactivity. In contrast, none of the individual
polymorphisms accounted for significant variability. Our
results show that biologically informed multilocus genetic
profiles have unique promise as indices of variability in
brain chemistry that may yield advances in mapping
individual differences in behaviorally relevant brain
function. In turn, such genetic profiles may fuel
gene-environment interactions research establishing
trajectories of risk for psychopathology.},
Language = {eng},
Doi = {10.1038/npp.2011.82},
Key = {Nikolova2011}
}
@article{Carre2011,
Author = {Carré, JM and McCormick, CM and Hariri, AR},
Title = {The social neuroendocrinology of human aggression.},
Journal = {Psychoneuroendocrinology},
Volume = {36},
Number = {7},
Pages = {935-944},
Address = {Department of Psychology and Neuroscience, Duke University,
Durham, NC, USA. justin.carre@duke.edu},
Year = {2011},
Month = {August},
ISSN = {0306-4530},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21367531},
Keywords = {Aggression/*physiology/psychology • Animals •
Competitive Behavior/physiology • Humans • Models,
Animal • Models, Biological • Neural
Pathways/metabolism/physiology • Neuroendocrinology
• Neurosecretory Systems/metabolism/*physiology •
*Social Behavior • Testosterone/blood/physiology},
Abstract = {Testosterone concentrations fluctuate rapidly in response to
competitive and aggressive interactions, suggesting that
changes in testosterone rather than baseline differences
shape ongoing and/or future competitive and aggressive
behaviors. Although recent experiments in animal models
provide compelling empirical support for this idea, studies
in humans have focused largely on how competitive
interactions drive changes in testosterone concentrations
and not how these changes influence subsequent behavior. In
this paper, we provide a review of the literature on
testosterone and human aggression with a main focus on the
role of testosterone dynamics in modulating reactive
aggression. We also speculate on one putative neural
mechanism through which testosterone may bias human
aggressive behavior. Finally, we conclude by highlighting
important questions that should be addressed in future
research.},
Language = {eng},
Doi = {10.1016/j.psyneuen.2011.02.001},
Key = {Carre2011}
}
@article{Hariri2011c,
Author = {Hariri, AR},
Title = {The what, where, and when of catechol-O-methyltransferase.},
Journal = {Biological psychiatry},
Volume = {70},
Number = {3},
Pages = {214-215},
Address = {Laboratory of NeuroGenetics, Department of Psychology and
Neuroscience, Institute for Genome Sciences and Policy, Duke
University, 417 Chapel Drive, Durham, NC 27708, USA.
ahmad.hariri@duke.edu},
Year = {2011},
Month = {August},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21745617},
Keywords = {Attention Deficit Disorder with Hyperactivity/*genetics
• Brain/*physiology • Catechol
O-Methyltransferase/*genetics • Central Nervous System
Stimulants/*therapeutic use • Female • Humans
• Male • Memory, Short-Term/*physiology •
Methylphenidate/*therapeutic use • *Polymorphism,
Single Nucleotide},
Language = {eng},
Doi = {10.1016/j.biopsych.2011.06.002},
Key = {Hariri2011c}
}
@article{Morey2011,
Author = {Morey, RA and Hariri, AR and Gold, AL and Hauser, MA and Munger, HJ and Dolcos, F and McCarthy, G},
Title = {Serotonin transporter gene polymorphisms and brain function
during emotional distraction from cognitive processing in
posttraumatic stress disorder.},
Journal = {BMC Psychiatry},
Volume = {11},
Pages = {76},
Address = {Department of Psychiatry and Behavioral Sciences, Duke
University, Durham, NC 27710, USA. morey@biac.duke.edu},
Year = {2011},
Month = {May},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21545724},
Keywords = {Amygdala/physiopathology • Case-Control Studies •
Cognition/*physiology • Emotions/*physiology •
Functional Neuroimaging/methods/psychology • Humans
• Magnetic Resonance Imaging/psychology • Memory,
Short-Term/physiology • *Polymorphism, Single
Nucleotide • Prefrontal Cortex/physiopathology •
Promoter Regions, Genetic/genetics/physiology •
Psychomotor Performance/physiology • September 11
Terrorist Attacks/psychology • Serotonin Plasma
Membrane Transport Proteins/genetics/*physiology •
Stress Disorders, Post-Traumatic/*genetics/*physiopathology/psychology
• Veterans/psychology • Wounds and
Injuries/physiopathology/psychology},
Abstract = {BACKGROUND: Serotonergic system dysfunction has been
implicated in posttraumatic stress disorder (PTSD). Genetic
polymorphisms associated with serotonin signaling may
predict differences in brain circuitry involved in emotion
processing and deficits associated with PTSD. In healthy
individuals, common functional polymorphisms in the
serotonin transporter gene (SLC6A4) have been shown to
modulate amygdala and prefrontal cortex (PFC) activity in
response to salient emotional stimuli. Similar patterns of
differential neural responses to emotional stimuli have been
demonstrated in PTSD but genetic factors influencing these
activations have yet to be examined. METHODS: We
investigated whether SLC6A4 promoter polymorphisms
(5-HTTLPR, rs25531) and several downstream single nucleotide
polymorphisms (SNPs) modulated activity of brain regions
involved in the cognitive control of emotion in post-9/11
veterans with PTSD. We used functional MRI to examine neural
activity in a PTSD group (n = 22) and a trauma-exposed
control group (n = 20) in response to trauma-related images
presented as task-irrelevant distractors during the active
maintenance period of a delayed-response working memory
task. Regions of interest were derived by contrasting
activation for the most distracting and least distracting
conditions across participants. RESULTS: In patients with
PTSD, when compared to trauma-exposed controls, rs16965628
(associated with serotonin transporter gene expression)
modulated task-related ventrolateral PFC activation and
5-HTTLPR tended to modulate left amygdala activation.
Subsequent to combat-related trauma, these SLC6A4
polymorphisms may bias serotonin signaling and the neural
circuitry mediating cognitive control of emotion in patients
with PTSD. CONCLUSIONS: The SLC6A4 SNP rs16965628 and
5-HTTLPR are associated with a bias in neural responses to
traumatic reminders and cognitive control of emotions in
patients with PTSD. Functional MRI may help identify
intermediate phenotypes and dimensions of PTSD that clarify
the functional link between genes and disease phenotype, and
also highlight features of PTSD that show more proximal
influence of susceptibility genes compared to current
clinical categorizations.},
Language = {eng},
Doi = {10.1186/1471-244X-11-76},
Key = {Morey2011}
}
@article{Gianaros2011,
Author = {Gianaros, PJ and Manuck, SB and Sheu, LK and Kuan, DCH and Votruba-Drzal, E and Craig, AE and Hariri, AR},
Title = {Parental education predicts corticostriatal functionality in
adulthood.},
Journal = {Cerebral cortex (New York, N.Y. : 1991)},
Volume = {21},
Number = {4},
Pages = {896-910},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA 15213, USA. gianarospj@upmc.edu},
Year = {2011},
Month = {April},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20810623},
Keywords = {Adult • Cerebral Cortex/*physiology • *Educational
Status • Female • Humans • Magnetic Resonance
Imaging • Male • Middle Aged • Neural
Pathways/*physiology • *Parents • Socioeconomic
Factors},
Abstract = {Socioeconomic disadvantage experienced in early development
predicts ill health in adulthood. However, the
neurobiological pathways linking early disadvantage to adult
health remain unclear. Lower parental education-a
presumptive indicator of early socioeconomic
disadvantage-predicts health-impairing adult behaviors,
including tobacco and alcohol dependencies. These behaviors
depend, in part, on the functionality of corticostriatal
brain systems that 1) show developmental plasticity and
early vulnerability, 2) process reward-related information,
and 3) regulate impulsive decisions and actions. Hence,
corticostriatal functionality in adulthood may covary
directly with indicators of early socioeconomic
disadvantage, particularly lower parental education. Here,
we tested the covariation between parental education and
corticostriatal activation and connectivity in 76 adults
without confounding clinical syndromes. Corticostriatal
activation and connectivity were assessed during the
processing of stimuli signaling monetary gains (positive
feedback [PF]) and losses (negative feedback). After
accounting for participants' own education and other
explanatory factors, lower parental education predicted
reduced activation in anterior cingulate and dorsomedial
prefrontal cortices during PF, along with reduced
connectivity between these cortices and orbitofrontal and
striatal areas implicated in reward processing and impulse
regulation. In speculation, adult alterations in
corticostriatal functionality may represent facets of a
neurobiological endophenotype linked to socioeconomic
conditions of early development.},
Language = {eng},
Doi = {10.1093/cercor/bhq160},
Key = {Gianaros2011}
}
@article{Drabant2011,
Author = {Drabant, EM and Kuo, JR and Ramel, W and Blechert, J and Edge, MD and Cooper, JR and Goldin, PR and Hariri, AR and Gross,
JJ},
Title = {Experiential, autonomic, and neural responses during threat
anticipation vary as a function of threat intensity and
neuroticism.},
Journal = {NeuroImage},
Volume = {55},
Number = {1},
Pages = {401-410},
Address = {Psychology Department, Stanford University, Stanford, CA
94305, USA. drabant@stanford.edu},
Year = {2011},
Month = {March},
ISSN = {1053-8119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21093595},
Keywords = {Brain/*physiopathology • *Fear • Female •
Humans • *Magnetic Resonance Imaging • Neurotic
Disorders/*physiopathology • *Personal Autonomy •
*Problem-Based Learning • Young Adult},
Abstract = {Anticipatory emotional responses play a crucial role in
preparing individuals for impending challenges. They do this
by triggering a coordinated set of changes in behavioral,
autonomic, and neural response systems. In the present
study, we examined the biobehavioral impact of varying
levels of anticipatory anxiety, using a shock anticipation
task in which unpredictable electric shocks were threatened
and delivered to the wrist at variable intervals and
intensities (safe, medium, strong). This permitted
investigation of a dynamic range of anticipatory anxiety
responses. In two studies, 95 and 51 healthy female
participants, respectively, underwent this shock
anticipation task while providing continuous ratings of
anxiety experience and electrodermal responding (Study 1)
and during fMRI BOLD neuroimaging (Study 2). Results
indicated a step-wise pattern of responding in anxiety
experience and electrodermal responses. Several brain
regions showed robust responses to shock anticipation
relative to safe trials, including the hypothalamus,
periaqueductal gray, caudate, precentral gyrus, thalamus,
insula, ventrolateral PFC, dorsomedial PFC, and ACC. A
subset of these regions demonstrated a linear pattern of
increased responding from safe to medium to strong trials,
including the bilateral insula, ACC, and inferior frontal
gyrus. These responses were modulated by individual
differences in neuroticism, such that those high in
neuroticism showed exaggerated anxiety experience across the
entire task, and reduced brain activation from medium to
strong trials in a subset of brain regions. These findings
suggest that individual differences in neuroticism may
influence sensitivity to anticipatory threat and provide new
insights into the mechanism through which neuroticism may
confer risk for developing anxiety disorders via
dysregulated anticipatory responses.},
Language = {eng},
Doi = {10.1016/j.neuroimage.2010.11.040},
Key = {Drabant2011}
}
@article{Hyde2011a,
Author = {Hyde, LW and Gorka, A and Manuck, SB and Hariri, AR},
Title = {Perceived social support moderates the link between
threat-related amygdala reactivity and trait
anxiety.},
Journal = {Neuropsychologia},
Volume = {49},
Number = {4},
Pages = {651-656},
Address = {Department of Psychology, University of Pittsburgh,
Pittsburgh, PA 15260, USA. lwh2@pitt.edu},
Year = {2011},
Month = {March},
ISSN = {0028-3932},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20813118},
Keywords = {*Adaptation, Psychological • Adult •
Aggression/*psychology • Amygdala/*physiology •
Anxiety/*psychology • Brain Mapping • Female
• Humans • Magnetic Resonance Imaging • Male
• Middle Aged • Reference Values • *Social
Support • Temperament},
Abstract = {Several lines of research have illustrated that negative
environments can precipitate psychopathology, particularly
in the context of relatively increased biological risk,
while social resources can buffer the effects of these
environments. However, little research has examined how
social resources might buffer proximal biological risk for
psychopathology or the neurobiological pathways through
which such buffering may be mediated. Here we report that
the expression of trait anxiety as a function of
threat-related amygdala reactivity is moderated by perceived
social support, a resource for coping with adversity. A
significant positive correlation between amygdala reactivity
and trait anxiety was evident in individuals reporting below
average levels of support but not in those reporting average
or above average levels. These results were consistent
across multiple measures of trait anxiety and were specific
to anxiety in that they did not extend to measures of broad
negative or positive affect. Our findings illuminate a
biological pathway, namely moderation of amygdala-related
anxiety, through which social support may confer resilience
to psychopathology. Moreover, our results indicate that
links between neural reactivity and behavior are not static
but rather may be contingent on social resources.},
Language = {eng},
Doi = {10.1016/j.neuropsychologia.2010.08.025},
Key = {Hyde2011a}
}
@article{Hariri2011a,
Author = {Hariri, AR and Whalen, PJ},
Title = {The amygdala: Inside and out},
Journal = {F1000 Biology Reports},
Volume = {3},
Number = {1},
Pages = {2},
Publisher = {Faculty of 1000, Ltd.},
Year = {2011},
Month = {February},
ISSN = {1740-4118},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21399763},
Abstract = {Research at the interface of psychology, neuroscience,
molecular biology, and genetics, focusing on the amygdala,
has begun to reveal a rule book for emotional reactions.
Variations in intrinsic and extrinsic factors tweak the
sensitivity of the amygdala, giving rise to differences in
behavior between individuals. At their most extreme, these
variations may generate psychological disorders, and even
our current rudimentary understanding of this brain region
suggests novel strategies for the treatment of such
disorders. © 2011 Faculty of 1000 Ltd.},
Language = {eng},
Doi = {10.3410/B3-2},
Key = {Hariri2011a}
}
@article{fds252004,
Author = {Hariri, AR and Whalen, PJ},
Title = {Face to face with the emotional brain},
Journal = {Scientist},
Volume = {25},
Number = {2},
Pages = {30},
Year = {2011},
Month = {February},
ISSN = {0890-3670},
Key = {fds252004}
}
@article{Beevers2011,
Author = {Beevers, CG and Marti, CN and Lee, H-J and Stote, DL and Ferrell, RE and Hariri, AR and Telch, MJ},
Title = {Associations between serotonin transporter gene promoter
region (5-HTTLPR) polymorphism and gaze bias for emotional
information.},
Journal = {Journal of abnormal psychology},
Volume = {120},
Number = {1},
Pages = {187-197},
Address = {Department of Psychology, University of Texas at Austin, 1
University Station, A8000, Austin, TX 78712, USA.
beevers@psy.utexas.edu},
Year = {2011},
Month = {February},
ISSN = {0021-843X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21319930},
Keywords = {Adult • Alleles • Analysis of Variance •
Attention/*physiology • Emotions/*physiology • Eye
Movements/*genetics • Facial Expression • Female
• Gene Frequency • Genotype • Humans •
Male • Photic Stimulation • *Polymorphism, Single
Nucleotide • Promoter Regions, Genetic • Serotonin
Plasma Membrane Transport Proteins/*genetics • Time
Factors},
Abstract = {The serotonin transporter promoter region polymorphism
(5-HTTLPR) is associated with neural response to negative
images in brain regions involved in the experience of
emotion. However, the behavioral implications of this
sensitivity have been studied far less extensively. The
current study used eye-tracking methodology to examine how
individuals genotyped for the 5-HTTLPR, including the single
nucleotide polymorphism (SNP) rs25531, allocated attention
during prolonged (30-s) exposure to face stimuli depicting
positive and negative emotion. Short 5-HTTLPR allele
carriers and carriers of the long allele with guanine at the
sixth nucleotide (S/LG) displayed a stronger gaze bias
(total fixation time, number of fixations, mean fixation
length) for positive than for sad, threat, or neutral
stimuli. In contrast, those homozygous for the long 5-HTTLPR
allele with adenine at the sixth nucleotide (LA) viewed the
emotion stimuli in an unbiased fashion. Time course analyses
indicated no initial 5-HTTLPR group differences; however,
S/LG 5-HTTLPR allele carriers were more likely than LA
5-HTTLPR homozygotes to direct gaze toward happy than toward
sad stimuli over time. This bias toward positive stimuli
during the later stages of information processing likely
reflects a strategic effort to downregulate heightened
reactivity to negative stimuli among 5-HTTLPR S/LG allele
carriers.},
Language = {eng},
Doi = {10.1037/a0022125},
Key = {Beevers2011}
}
@article{Hariri2011b,
Author = {Hariri, AR and Shin, LM},
Title = {Welcome to biology of mood \& anxiety disorders},
Journal = {Biology of mood \& anxiety disorders},
Volume = {1},
Number = {1},
Pages = {1},
Publisher = {Springer Science and Business Media LLC},
Address = {Laboratory of NeuroGenetics, Department of Psychology \&
Neuroscience, Institute for Genome Sciences \& Policy, Duke
University, Durham, NC USA. ahmad.hariri@duke.edu.},
Year = {2011},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22738418},
Language = {eng},
Doi = {10.1186/2045-5380-1-1},
Key = {Hariri2011b}
}
@article{fds252110,
Author = {Carre, JM and Murphy, KR and Hariri, AR},
Title = {What lies beneath the face of aggression?},
Journal = {Social cognitive and affective neuroscience},
Volume = {8},
Number = {2},
Pages = {224-229},
Year = {2011},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22198969},
Abstract = {Recent evidence indicates that a sexually dimorphic feature
of humans, the facial width-to-height ratio (FWHR), is
positively correlated with reactive aggression, particularly
in men. Also, predictions about the aggressive tendencies of
others faithfully map onto FWHR in the absence of explicit
awareness of this metric. Here, we provide the first
evidence that amygdala reactivity to social signals of
interpersonal challenge may underlie the link between
aggression and the FWHR. Specifically, amygdala reactivity
to angry faces was positively correlated with aggression,
but only among men with relatively large FWHRs. The patterns
of association were specific to angry facial expressions and
unique to men. These links may reflect the common influence
of pubertal testosterone on craniofacial growth and
development of neural circuitry underlying aggression.
Amygdala reactivity may also represent a plausible pathway
through which FWHR may have evolved to represent an honest
indicator of conspecific threat, namely by reflecting the
responsiveness of neural circuitry mediating aggressive
behavior.},
Doi = {10.1093/scan/nsr096},
Key = {fds252110}
}
@article{Fisher2011,
Author = {Fisher, PM and Price, JC and Meltzer, CC and Moses Kolko and EL and Becker,
C and Berga, SL and Hariri, AR},
Title = {Medial prefrontal cortex serotonin 1A and 2A receptor
binding interacts to predict threat-related amygdala
reactivity},
Journal = {Biology of mood \& anxiety disorders},
Volume = {1},
Number = {1},
Pages = {2},
Publisher = {Springer Science and Business Media LLC},
Address = {Center for Neuroscience, University of Pittsburgh,
Pittsburgh, Pennsylvania 15260, USA. patrick.fisher@gmail.com.},
Year = {2011},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22738071},
Abstract = {BACKGROUND: The amygdala and medial prefrontal cortex (mPFC)
comprise a key corticolimbic circuit that helps shape
individual differences in sensitivity to threat and the
related risk for psychopathology. Although serotonin (5-HT)
is known to be a key modulator of this circuit, the specific
receptors mediating this modulation are unclear. The
colocalization of 5-HT1A and 5-HT2A receptors on mPFC
glutamatergic neurons suggests that their functional
interactions may mediate 5-HT effects on this circuit
through top-down regulation of amygdala reactivity. Using a
multimodal neuroimaging strategy in 39 healthy volunteers,
we determined whether threat-related amygdala reactivity,
assessed with blood oxygen level-dependent functional
magnetic resonance imaging, was significantly predicted by
the interaction between mPFC 5-HT1A and 5-HT2A receptor
levels, assessed by positron emission tomography. RESULTS:
5-HT1A binding in the mPFC significantly moderated an
inverse correlation between mPFC 5-HT2A binding and
threat-related amygdala reactivity. Specifically, mPFC
5-HT2A binding was significantly inversely correlated with
amygdala reactivity only when mPFC 5-HT1A binding was
relatively low. CONCLUSIONS: Our findings provide evidence
that 5-HT1A and 5-HT2A receptors interact to shape
serotonergic modulation of a functional circuit between the
amygdala and mPFC. The effect of the interaction between
mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is
consistent with the colocalization of these receptors on
glutamatergic neurons in the mPFC.},
Language = {eng},
Doi = {10.1186/2045-5380-1-2},
Key = {Fisher2011}
}
@article{Cornelius2010,
Author = {Cornelius, JR and Aizenstein, HJ and Hariri, AR},
Title = {Amygdala reactivity is inversely related to level of
cannabis use in individuals with comorbid cannabis
dependence and major depression.},
Journal = {Addictive behaviors},
Volume = {35},
Number = {6},
Pages = {644-646},
Address = {Department of Psychiatry, University of Pittsburgh School of
Medicine, Pittsburgh, PA 15213, United States.
corneliusjr@upmc.edu},
Year = {2010},
Month = {June},
ISSN = {0306-4603},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20189314},
Keywords = {Amygdala/*drug effects/physiopathology • Antidepressive
Agents, Second-Generation/therapeutic use •
Cannabis/*adverse effects • Comorbidity •
Depressive Disorder/drug therapy/epidemiology •
Diagnosis, Dual (Psychiatry) • Double-Blind Method
• Fear/*drug effects • Female •
Fluoxetine/therapeutic use • Humans • Magnetic
Resonance Imaging/methods • Male • Marijuana
Abuse/epidemiology/*physiopathology • Social Behavior
• Young Adult},
Abstract = {Phan et al. (2008) recently reported that an acute dose of
oral THC is associated with a decrease in threat-related
amygdala reactivity during a social threat stimulus task.
However, to date, those findings have not been replicated,
and have not been extended to clinical studies involving
smoked rather than oral cannabis. In this study, we
hypothesized that level of cannabis smoked by participants
in our treatment study would be inversely related to the
level of threat-related amygdala reactivity. Subjects were
recruited from among participants in our double-blind,
placebo-controlled trial of fluoxetine in comorbid youth
with cannabis dependence/major depression. The
threat-related amygdala reactivity task used by Hariri et
al. (2009) was completed during BOLD fMRI scans at study
baseline and then again 12 weeks later at the end of the
trial. Data are available from six subjects with pre-and
post-treatment fMRI data. During the course of the study,
five of the six subjects demonstrated a decrease in their
level of cannabis use, with a mean decrease of 64%, and
those persons all demonstrated an increase in their level of
amygdala reactivity. One subject demonstrated an increase in
their level of cannabis use (a 79% increase) during the
treatment trial, and that person demonstrated a decrease in
their level of amygdala reactivity. Thus, a higher level of
cannabis use was consistently associated with a lower level
of amygdala reactivity across all subjects (matched pairs t
= 2.70, df = 5, p < 0.05, two-tailed). These findings are
consistent with the reports by Phan et al. (2008) and Hariri
et al. (2009) suggesting that cannabinoids have an
inhibitory effect on threat-related amygdala
reactivity.},
Language = {eng},
Doi = {10.1016/j.addbeh.2010.02.004},
Key = {Cornelius2010}
}
@article{Chiao2010,
Author = {Chiao, JY and Hariri, AR and Harada, T and Mano, Y and Sadato, N and Parrish, TB and Iidaka, T},
Title = {Theory and methods in cultural neuroscience.},
Journal = {Social cognitive and affective neuroscience},
Volume = {5},
Number = {2-3},
Pages = {356-361},
Address = {Department of Psychology and Interdepartmental Neuroscience
Program, Northwestern University, Evanston, IL 60208, USA.
jchiao@northwestern.edu},
Year = {2010},
Month = {June},
ISSN = {1749-5016},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20592044},
Keywords = {Brain/physiology • Brain Mapping • Cross-Cultural
Comparison • *Culture • Humans • Magnetic
Resonance Imaging • Neurosciences/*methods •
Polymorphism, Genetic/genetics • Research Design •
Stereotyping},
Abstract = {Cultural neuroscience is an emerging research discipline
that investigates cultural variation in psychological,
neural and genomic processes as a means of articulating the
bidirectional relationship of these processes and their
emergent properties. Research in cultural neuroscience
integrates theory and methods from anthropology, cultural
psychology, neuroscience and neurogenetics. Here, we review
a set of core theoretical and methodological challenges
facing researchers when planning and conducting cultural
neuroscience studies, and provide suggestions for overcoming
these challenges. In particular, we focus on the problems of
defining culture and culturally appropriate experimental
tasks, comparing neuroimaging data acquired from different
populations and scanner sites and identifying functional
genetic polymorphisms relevant to culture. Implications of
cultural neuroscience research for addressing current issues
in population health disparities are discussed.},
Language = {eng},
Doi = {10.1093/scan/nsq063},
Key = {Chiao2010}
}
@article{fds252003,
Author = {Jedema, HP and Gianaros, PJ and Greer, PJ and Kerr, DD and Liu, S and Higley, JD and Suomi, SJ and Olsen, AS and Porter, JN and Lopresti, BJ and Hariri, AR and Bradberry, CW},
Title = {Morphological differences associated with a serotonin
transporter polymorphism (5-HTTLPR) in rhesus
macaques},
Journal = {Molecular Psychiatry},
Volume = {15},
Number = {5},
Pages = {446},
Publisher = {Springer Nature},
Year = {2010},
Month = {May},
ISSN = {1359-4184},
Doi = {10.1038/mp.2010.49},
Key = {fds252003}
}
@article{Jedema2010,
Author = {Jedema, HP and Gianaros, PJ and Greer, PJ and Kerr, DD and Liu, S and Higley, JD and Suomi, SJ and Olsen, AS and Porter, JN and Lopresti, BJ and Hariri, AR and Bradberry, CW},
Title = {Cognitive impact of genetic variation of the serotonin
transporter in primates is associated with differences in
brain morphology rather than serotonin neurotransmission.},
Journal = {Molecular psychiatry},
Volume = {15},
Number = {5},
Pages = {512-446},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA 15261, USA.},
Year = {2010},
Month = {May},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19721434},
Keywords = {Animals • Avoidance Learning/physiology •
Behavior, Animal/physiology • Benzylamines/metabolism
• Brain/drug effects/radionuclide imaging • Brain
Mapping • Carbon Isotopes/metabolism • Choice
Behavior/*physiology • Cognition/*physiology •
Genotype • Macaca mulatta • Magnetic Resonance
Imaging/methods • Male • Neuropsychological Tests
• Piperazines/metabolism • Polymorphism,
Genetic/*genetics • Positron-Emission
Tomography/methods • Protein Binding/drug
effects/genetics • Pyridines/metabolism •
Receptor, Serotonin, 5-HT1A/genetics •
Serotonin/genetics/*metabolism • Serotonin Plasma
Membrane Transport Proteins/*genetics • Synaptic
Transmission/*genetics • Time Factors •
Tritium/metabolism},
Abstract = {A powerful convergence of genetics, neuroimaging and
epidemiological research has identified the biological
pathways mediating individual differences in complex
behavioral processes and the related risk for disease.
Orthologous genetic variation in non-human primates (NHPs)
represents a unique opportunity to characterize the detailed
molecular and cellular mechanisms that bias behaviorally and
clinically relevant brain function. We report that a rhesus
macaque orthologue of a common polymorphism of the serotonin
transporter gene (rh5-HTTLPR) has strikingly similar effects
on behavior and brain morphology to those in humans.
Specifically, the rh5-HTTLPR (S)hort allele broadly affects
cognitive choice behavior and brain morphology without
observably affecting the 5-hydroxytryptamine (5-HT)
transporter or 5-HT(1A) concentrations in vivo.
Collectively, our findings indicate that 5-HTTLPR-associated
behavioral effects reflect genotype-dependent biases in
cortical development rather than static differences in
serotonergic signaling mechanisms. Moreover, these data
highlight the vast potential of NHP models in advancing our
understanding of human genetic variation affecting behavior
and neuropsychiatric disease liability.},
Language = {eng},
Doi = {10.1038/mp.2009.90},
Key = {Jedema2010}
}
@article{Caspi2010,
Author = {Caspi, A and Hariri, AR and Holmes, A and Uher, R and Moffitt,
TE},
Title = {Genetic sensitivity to the environment: the case of the
serotonin transporter gene and its implications for studying
complex diseases and traits.},
Journal = {The American journal of psychiatry},
Volume = {167},
Number = {5},
Pages = {509-527},
Address = {Department of Psychology, and Institute for Genome Sciences
and Policy, Duke University, Durham, NC 27708, USA.
ac115@duke.edu},
Year = {2010},
Month = {May},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20231323},
Keywords = {Animals • Brain/pathology/physiopathology •
Depressive Disorder/genetics • Environment •
Genetic Predisposition to Disease/*genetics •
Genome-Wide Association Study/methods • Genotype •
Humans • Models, Psychological • Mood
Disorders/genetics • Primates/genetics/psychology
• Serotonin Plasma Membrane Transport
Proteins/*genetics/physiology • Stress,
Psychological/complications/*genetics},
Abstract = {Evidence of marked variability in response among people
exposed to the same environmental risk implies that
individual differences in genetic susceptibility might be at
work. The study of such Gene-by-Environment (GxE)
interactions has gained momentum. In this article, the
authors review research about one of the most extensive
areas of inquiry: variation in the promoter region of the
serotonin transporter gene (SLC6A4; also known as 5-HTT) and
its contribution to stress sensitivity. Research in this
area has both advanced basic science and generated broader
lessons for studying complex diseases and traits. The
authors evaluate four lines of evidence about the 5-HTT
stress-sensitivity hypothesis: 1) observational studies
about the serotonin transporter linked polymorphic region
(5-HTTLPR), stress sensitivity, and depression in humans; 2)
experimental neuroscience studies about the 5-HTTLPR and
biological phenotypes relevant to the human stress response;
3) studies of 5-HTT variation and stress sensitivity in
nonhuman primates; and 4) studies of stress sensitivity and
genetically engineered 5-HTT mutations in rodents. The
authors then dispel some misconceptions and offer
recommendations for GxE research. The authors discuss how
GxE interaction hypotheses can be tested with large and
small samples, how GxE research can be carried out before as
well as after replicated gene discovery, the uses of GxE
research as a tool for gene discovery, the importance of
construct validation in evaluating GxE research, and the
contribution of GxE research to the public understanding of
genetic science.},
Language = {eng},
Doi = {10.1176/appi.ajp.2010.09101452},
Key = {Caspi2010}
}
@article{Munoz2010,
Author = {Muñoz, KE and Meyer-Lindenberg, A and Hariri, AR and Mervis, CB and Mattay, VS and Morris, CA and Berman, KF},
Title = {Abnormalities in neural processing of emotional stimuli in
Williams syndrome vary according to social vs. non-social
content.},
Journal = {NeuroImage},
Volume = {50},
Number = {1},
Pages = {340-346},
Address = {Section on Integrative Neuroimaging, National Institute of
Mental Health, NIH, DHHS, Bethesda, MD 20892,
USA.},
Year = {2010},
Month = {March},
ISSN = {1053-8119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20004252},
Keywords = {Adult • Amygdala/physiopathology •
Brain/*physiopathology • Brain Mapping •
Cognition/*physiology • Emotions/*physiology •
Female • Humans • Intelligence • Intelligence
Tests • Magnetic Resonance Imaging • Male •
Neural Pathways/physiopathology • Oxygen/blood •
Prefrontal Cortex/physiopathology • *Social Behavior
• Visual Perception/physiology • Williams
Syndrome/*physiopathology},
Abstract = {Williams syndrome (WS) is a rare genetic disorder caused by
the deletion of approximately 25 genes on chromosome 7q11.23
and is characterized by both hypersociability and increases
in specific phobia and anticipatory anxiety regarding
non-social entities or circumstances. Alterations in
amygdala reactivity and prefrontal regulation consistent
with the observed behavioral pattern of social versus
non-social abnormalities have been previously demonstrated
in individuals with WS (Meyer-Lindenberg et al., 2005).
However, in that study, the social stimulus (faces) matching
task was more difficult than the non-social scene (IAPS
stimuli) matching task, making it impossible to disambiguate
the relative contributions of task difficulty and stimulus
type (social versus non-social). In the present study, we
examined the performance of the same group of participants
with WS and normal IQs during a more cognitively demanding
task using the same scene stimuli as in the prior study.
Confirming previous findings, the results indicated (a) a
differential response of prefrontal regions as a function of
task difficulty and (b) a persistently increased activation
of the amygdala to non-social scenes by individuals with WS
regardless of cognitive load. These data provide further
evidence of disruption in amygdala-prefrontal circuitry in
individuals with WS.},
Language = {eng},
Doi = {10.1016/j.neuroimage.2009.11.069},
Key = {Munoz2010}
}
@article{Hariri2010,
Author = {Hariri, AR},
Title = {Genetic polymorphisms: a cornerstone of translational
biobehavioral research.},
Journal = {Science translational medicine},
Volume = {2},
Number = {18},
Pages = {18ps6},
Address = {Department of Psychology and Neuroscience, Institute for
Genome Sciences and Policy, Duke University, Durham, NC
27708, USA. ahmad.hariri@duke.edu},
Year = {2010},
Month = {February},
ISSN = {1946-6234},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20371481},
Keywords = {Amino Acid Substitution/genetics • Animals •
*Behavior • Brain-Derived Neurotrophic Factor/genetics
• Humans • Mice • *Polymorphism, Genetic
• *Translational Medical Research},
Abstract = {A new generation of interdisciplinary research seeks to use
common functional genetic polymorphisms to model emergent
variability in brain chemistry that regulates behaviorally
relevant brain structure and function. This genetically
mediated variability is then being mapped onto trajectories
of risk for psychopathology, especially that precipitated by
environmental adversity. This Perspective highlights a
recent paper in Science that provides a powerful example of
how a common functional genetic polymorphism can serve as a
translational bridge between human and mouse research,
extending our understanding of biological pathways that
mediate individual differences in behavior and in risk for
psychopathology.},
Language = {eng},
Doi = {10.1126/scitranslmed.3000811},
Key = {Hariri2010}
}
@article{Manuck2010,
Author = {Manuck, SB and Marsland, AL and Flory, JD and Gorka, A and Ferrell, RE and Hariri, AR},
Title = {Salivary testosterone and a trinucleotide (CAG) length
polymorphism in the androgen receptor gene predict amygdala
reactivity in men.},
Journal = {Psychoneuroendocrinology},
Volume = {35},
Number = {1},
Pages = {94-104},
Address = {Department of Psychology, University of Pittsburgh,
Pittsburgh, PA 15260, United States. Manuck@pitt.edu},
Year = {2010},
Month = {January},
ISSN = {0306-4530},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19493626},
Keywords = {Adult • Amygdala/*physiology • DNA/genetics •
Facial Expression • Genotype • Humans • Image
Processing, Computer-Assisted • Individuality •
Magnetic Resonance Imaging • Male • Middle Aged
• Oxygen/blood • Polymorphism, Genetic •
Receptors, Androgen/*genetics/physiology •
Saliva/*metabolism • Social Perception •
Testosterone/*metabolism • Trinucleotide
Repeats/*genetics},
Abstract = {In studies employing functional magnetic resonance imaging
(fMRI), reactivity of the amygdala to threat-related sensory
cues (viz., facial displays of negative emotion) has been
found to correlate positively with interindividual
variability in testosterone levels of women and young men
and to increase on acute administration of exogenous
testosterone. Many of the biological actions of testosterone
are mediated by intracellular androgen receptors (ARs),
which exert transcriptional control of androgen-dependent
genes and are expressed in various regions of the brain,
including the amygdala. Transactivation potential of the AR
decreases (yielding relative androgen insensitivity) with
expansion a polyglutamine stretch in the N-terminal domain
of the AR protein, as encoded by a trinucleotide (CAG)
repeat polymorphism in exon 1 of the X-chromosome AR gene.
Here we examined whether amygdala reactivity to
threat-related facial expressions (fear, anger) differs as a
function of AR CAG length variation and endogenous
(salivary) testosterone in a mid-life sample of 41 healthy
men (mean age=45.6 years, range: 34-54 years; CAG repeats,
range: 19-29). Testosterone correlated inversely with
participant age (r=-0.39, p=0.012) and positively with
number of CAG repeats (r=0.45, p=0.003). In partial
correlations adjusted for testosterone level, reactivity in
the ventral amygdala was lowest among men with largest
number of CAG repeats. This inverse association was seen in
both the right (r(p)=-0.34, p<0.05) and left (r(p)=-0.32,
p<0.05) hemisphere. Activation of dorsal amygdala,
correlated positively with individual differences in
salivary testosterone, also in right (r=0.40, p<0.02) and
left (r=0.32, p<0.05) hemisphere, but was not affected by
number of CAG repeats. Hence, androgenic influences on
threat-related reactivity in the ventral amygdala may be
moderated partially by CAG length variation in the AR gene.
Because individual differences in salivary testosterone also
predicted dorsal amygdala reactivity and did so
independently of CAG repeats, it is suggested that
androgenic influences within this anatomically distinct
region may be mediated, in part, by non-genomic or
AR-independent mechanisms.},
Language = {eng},
Doi = {10.1016/j.psyneuen.2009.04.013},
Key = {Manuck2010}
}
@article{Salgado-Pineda2010,
Author = {Salgado-Pineda, P and Fakra, E and Delaveau, P and Hariri, AR and Blin,
O},
Title = {Differential patterns of initial and sustained responses in
amygdala and cortical regions to emotional stimuli in
schizophrenia patients and healthy participants.},
Journal = {Journal of psychiatry & neuroscience : JPN},
Volume = {35},
Number = {1},
Pages = {41-48},
Address = {Centre d'Investigation Clinique-Unite de Pharmacologie
Clinique et d'Evaluations Therapeutiques, Hopital de la
Timone, Unite Mixte de Recherche, Centre national de la
recherche scientifique, 6193 Institut de Neurosciences
Cognitives de la Mediterranee, Ma},
Year = {2010},
Month = {January},
ISSN = {1180-4882},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20040245},
Keywords = {Adult • Amygdala/*physiopathology • Brain Mapping
• Cerebral Cortex/*physiopathology •
Emotions/*physiology • Executive Function/*physiology
• Facial Expression • Female • Humans •
Magnetic Resonance Imaging • Male • Middle Aged
• Neural Pathways/physiopathology •
Neuropsychological Tests • Pattern Recognition,
Visual/physiology • Psychiatric Status Rating Scales
• Reaction Time • Schizophrenia/*physiopathology
• Time Factors • Young Adult},
Abstract = {<h4>Background</h4>We sought to investigate the altered
brain responses to emotional stimuli in patients with
schizophrenia.<h4>Methods</h4>We analyzed data from 14
patients with schizophrenia and 14 healthy controls who
performed an emotional face matching task. We evaluated
brain activity and connectivity in the amygdala and cortical
regions during the initial (first 21 seconds of each
stimulation block) and sustained (last 21 seconds) stages of
an emotional processing task, and we determined changes in
amygdala activity across the emotional processing
task.<h4>Results</h4>The patients with schizophrenia showed
similar amygdala activation to the controls during the
initial stage of processing, but their activation decreased
during the sustained stage. The controls showed increasing
amygdala activity across the emotional blocks, whereas
activity progressively decreased in the schizophrenia group.
The patients with schizophrenia showed increased cortical
activity and interconnectivity in the medial frontal and
inferior parietal cortex in the initial stage of emotional
processing.There was increased activity in the superior
temporal cortex and greater connectivity with the inferior
parietal cortex in the sustained stage. Performance accuracy
was lower in the schizophrenia group in the first part of
the block, while their reaction time was longer in the
latter part of the block.<h4>Limitations</h4>It was not
possible to specify the moment at which the switch in
amygdala response occurred.<h4>Conclusion</h4>Our findings
suggest that patients with schizophrenia have an initial
automatic emotional response but that they need to switch to
a compensatory cognitive strategy to solve the
task.},
Language = {eng},
Doi = {10.1503/jpn.090017},
Key = {Salgado-Pineda2010}
}
@article{fds251972,
Author = {Hariri, A},
Title = {Imaging Genetics: Integration of Neuroimaging and Genetics
in the Search for Predictive Markers},
Pages = {532-537},
Publisher = {Elsevier},
Year = {2009},
Month = {December},
Doi = {10.1016/B978-0-12-369420-1.00047-0},
Key = {fds251972}
}
@article{fds252002,
Author = {Hariri, AR},
Title = {Ahmad R. Hariri: award for distinguished scientific early
career contributions to psychology.},
Journal = {The American psychologist},
Volume = {64},
Number = {8},
Pages = {683-684},
Year = {2009},
Month = {November},
ISSN = {0003-066X},
Doi = {10.1037/a0016290},
Key = {fds252002}
}
@article{Blasi2009,
Author = {Blasi, G and Hariri, AR and Alce, G and Taurisano, P and Sambataro, F and Das, S and Bertolino, A and Weinberger, DR and Mattay,
VS},
Title = {Preferential amygdala reactivity to the negative assessment
of neutral faces.},
Journal = {Biological psychiatry},
Volume = {66},
Number = {9},
Pages = {847-853},
Address = {Psychiatric Neuroscience Group, Department of Neurological
and Psychiatric Sciences, University of Bari, Bari,
Italy.},
Year = {2009},
Month = {November},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19709644},
Keywords = {Adult • Amygdala/*physiology • Brain Mapping
• Decision Making/*physiology • Emotions •
*Facial Expression • Female • Gyrus
Cinguli/physiology • Humans • Magnetic Resonance
Imaging • Male • Neural Pathways/physiology •
Prefrontal Cortex/physiology • Prejudice •
Reaction Time • Social Perception},
Abstract = {<h4>Background</h4>Prior studies suggest that the amygdala
shapes complex behavioral responses to socially ambiguous
cues. We explored human amygdala function during explicit
behavioral decision making about discrete emotional facial
expressions that can represent socially unambiguous and
ambiguous cues.<h4>Methods</h4>During functional magnetic
resonance imaging, 43 healthy adults were required to make
complex social decisions (i.e., approach or avoid) about
either relatively unambiguous (i.e., angry, fearful, happy)
or ambiguous (i.e., neutral) facial expressions. Amygdala
activation during this task was compared with that elicited
by simple, perceptual decisions (sex discrimination) about
the identical facial stimuli.<h4>Results</h4>Angry and
fearful expressions were more frequently judged as avoidable
and happy expressions most often as approachable. Neutral
expressions were equally judged as avoidable and
approachable. Reaction times to neutral expressions were
longer than those to angry, fearful, and happy expressions
during social judgment only. Imaging data on stimuli judged
to be avoided revealed a significant task by emotion
interaction in the amygdala. Here, only neutral facial
expressions elicited greater activity during social judgment
than during sex discrimination. Furthermore, during social
judgment only, neutral faces judged to be avoided were
associated with greater amygdala activity relative to
neutral faces that were judged as approachable. Moreover,
functional coupling between the amygdala and both
dorsolateral prefrontal (social judgment > sex
discrimination) and cingulate (sex discrimination > social
judgment) cortices was differentially modulated by task
during processing of neutral faces.<h4>Conclusions</h4>Our
results suggest that increased amygdala reactivity and
differential functional coupling with prefrontal circuitries
may shape complex decisions and behavioral responses to
socially ambiguous cues.},
Language = {eng},
Doi = {10.1016/j.biopsych.2009.06.017},
Key = {Blasi2009}
}
@article{Fisher2009,
Author = {Fisher, PM and Meltzer, CC and Price, JC and Coleman, RL and Ziolko, SK and Becker, C and Moses-Kolko, EL and Berga, SL and Hariri,
AR},
Title = {Medial prefrontal cortex 5-HT(2A) density is correlated with
amygdala reactivity, response habituation, and functional
coupling.},
Journal = {Cerebral cortex (New York, N.Y. : 1991)},
Volume = {19},
Number = {11},
Pages = {2499-2507},
Address = {Center for Neuroscience, University of Pittsburgh,
Pittsburgh, PA 15213, USA.},
Year = {2009},
Month = {November},
ISSN = {1047-3211},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19321655},
Keywords = {Adult • Amygdala/*physiology •
Emotions/*physiology • Female • Habituation,
Psychophysiologic/*physiology • Humans • Male
• Neural Inhibition/*physiology • Prefrontal
Cortex/*physiology • Receptor, Serotonin,
5-HT2A/*metabolism • Tissue Distribution},
Abstract = {Feedback inhibition of the amygdala via medial prefrontal
cortex (mPFC) is an important component in the regulation of
complex emotional behaviors. The functional dynamics of this
corticolimbic circuitry are, in part, modulated by serotonin
(5-HT). Serotonin 2A (5-HT(2A)) receptors within the mPFC
represent a potential molecular mechanism through which 5-HT
can modulate this corticolimbic circuitry. We employed a
multimodal neuroimaging strategy to explore the relationship
between threat-related amygdala reactivity, assessed using
blood oxygen level-dependent functional magnetic resonance
imaging, and mPFC 5-HT(2A) density, assessed using
[(18)F]altanserin positron emission tomography in 35 healthy
adult volunteers. We observed a significant inverse
relationship wherein greater mPFC 5-HT(2A) density was
associated with reduced threat-related right amygdala
reactivity. Remarkably, 25-37% of the variability in
amygdala reactivity was explained by mPFC 5-HT(2A) density.
We also observed a positive correlation between mPFC
5-HT(2A) density and the magnitude of right amygdala
habituation. Furthermore, functional coupling between the
amygdala and mPFC was positively correlated with 5-HT(2A)
density suggesting that effective integration of emotionally
salient information within this corticolimbic circuitry may
be modulated, at least in part, by mPFC 5-HT(2A).
Collectively, our results indicate that mPFC 5-HT(2A) is
strongly associated with threat-related amygdala reactivity
as well as its temporal habituation and functional coupling
with prefrontal regulatory regions.},
Language = {eng},
Doi = {10.1093/cercor/bhp022},
Key = {Fisher2009}
}
@article{Mechelli2009,
Author = {Mechelli, A and Tognin, S and McGuire, PK and Prata, D and Sartori, G and Fusar-Poli, P and De Brito and S and Hariri, AR and Viding,
E},
Title = {Genetic vulnerability to affective psychopathology in
childhood: a combined voxel-based morphometry and functional
magnetic resonance imaging study.},
Journal = {Biological psychiatry},
Volume = {66},
Number = {3},
Pages = {231-237},
Address = {Department of Psychology, Institute of Psychiatry, PO Box
67, Division of Psychological Medicine and Psychiatry,
King's College London, 103 Denmark Hill, London SE5 8AF,
United Kingdom. a.mechelli@iop.kcl.ac.uk},
Year = {2009},
Month = {August},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19278671},
Keywords = {Affective Disorders, Psychotic/*genetics/*pathology •
Brain/*blood supply/*pathology • Brain Mapping •
Catechol O-Methyltransferase/*genetics • Child •
Genotype • Humans • Image Processing,
Computer-Assisted/methods • Longitudinal Studies •
Magnetic Resonance Imaging/methods • Male •
Methionine/genetics • Neuropsychological Tests •
Oxygen/blood • Photic Stimulation • Polymorphism,
Genetic/*drug effects • Reaction Time/physiology •
Twin Studies as Topic • Valine/genetics},
Abstract = {<h4>Background</h4>The majority of affective psychopathology
is rooted early in life and first emerges during childhood
and adolescence. However, little is known about how genetic
vulnerability affects brain structure and function in
childhood since the vast majority of studies published so
far have been conducted on adult participants. The present
investigation examined for the first time the effects of
catechol-O-methyltransferase (COMT) valine (val) 158
methionine (met) (val158met) polymorphism, which has been
shown to moderate predisposition to negative mood and
affective disorders, on brain structure and function in
children.<h4>Methods</h4>Voxel-based morphometry and
functional magnetic resonance imaging were used to measure
gray matter volume and emotional reactivity in 50 children
aged between 10 and 12 years. We tested the hypothesis that
met158 allele affects structural brain development and
confers heightened reactivity within the affective
frontolimbic circuit in children.<h4>Results</h4>The met158
allele was positively associated with gray matter volume in
the left hippocampal head where genotype accounted for 59%
of interindividual variance. In addition, the met158 allele
was positively associated with neuronal responses to fearful
relative to neutral facial expressions in the right
parahippocampal gyrus where genotype accounted for 14% of
the interindividual variance.<h4>Conclusions</h4>These
results indicate that the met158 allele is associated with
increased gray matter volume and heightened reactivity
during emotional processing within the limbic system in
children as young as 10 to 12 years of age. These findings
are consistent with the notion that genetic factors affect
brain function to moderate vulnerability to affective
psychopathology from childhood.},
Language = {eng},
Doi = {10.1016/j.biopsych.2009.01.033},
Key = {Mechelli2009}
}
@article{Hariri2009a,
Author = {Hariri, AR and Gorka, A and Hyde, LW and Kimak, M and Halder, I and Ducci,
F and Ferrell, RE and Goldman, D and Manuck, SB},
Title = {Divergent effects of genetic variation in endocannabinoid
signaling on human threat- and reward-related brain
function.},
Journal = {Biological psychiatry},
Volume = {66},
Number = {1},
Pages = {9-16},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15213, USA. haririar@upmc.edu},
Year = {2009},
Month = {July},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19103437},
Keywords = {Adult • Amidohydrolases/*genetics • Analysis of
Variance • Anxiety/*genetics • Brain/anatomy \&
histology/blood supply/*physiology • Brain Mapping
• Cannabinoid Receptor Modulators/genetics •
Endocannabinoids • Female • Genetic
Variation/*genetics • Genotype • Humans •
Image Processing, Computer-Assisted/methods • Magnetic
Resonance Imaging/methods • Male • Middle Aged
• Oxygen/blood • Psychiatric Status Rating Scales
• Regression Analysis • *Reward • *Signal
Transduction/genetics},
Abstract = {<h4>Background</h4>Fatty acid amide hydrolase (FAAH) is a
key enzyme in regulating endocannabinoid (eCB) signaling. A
common single nucleotide polymorphism (C385A) in the human
FAAH gene has been associated with increased risk for
addiction and obesity.<h4>Methods</h4>Using imaging genetics
in 82 healthy adult volunteers, we examined the effects of
FAAH C385A on threat- and reward-related human brain
function.<h4>Results</h4>Carriers of FAAH 385A, associated
with reduced enzyme and possibly increased eCB signaling,
had decreased threat-related amygdala reactivity but
increased reward-related ventral striatal reactivity in
comparison with C385 homozygotes. Similarly divergent
effects of FAAH C385A genotype were manifest at the level of
brain-behavior relationships. The 385A carriers showed
decreased correlation between amygdala reactivity and trait
anxiety but increased correlation between ventral striatal
reactivity and delay discounting, an index of
impulsivity.<h4>Conclusions</h4>Our results parallel
pharmacologic and genetic dissection of eCB signaling, are
consistent with the psychotropic effects of
Delta(9)-tetrahydrocannabinol, and highlight specific neural
mechanisms through which variability in eCB signaling
impacts complex behavioral processes related to risk for
addiction and obesity.},
Language = {eng},
Doi = {10.1016/j.biopsych.2008.10.047},
Key = {Hariri2009a}
}
@article{Gianaros2009,
Author = {Gianaros, PJ and Hariri, AR and Sheu, LK and Muldoon, MF and Sutton-Tyrrell, K and Manuck, SB},
Title = {Preclinical atherosclerosis covaries with individual
differences in reactivity and functional connectivity of the
amygdala.},
Journal = {Biological psychiatry},
Volume = {65},
Number = {11},
Pages = {943-950},
Address = {Department of Psychiatry and Psychology, University of
Pittsburgh, 3811 O'Hara Street, Pittsburgh, Pennsylvania
15213, USA. gianarospj@upmc.edu},
Year = {2009},
Month = {June},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19013557},
Keywords = {Adult • Amygdala/blood supply/*physiopathology •
Atherosclerosis/epidemiology/*pathology • Brain Mapping
• Carotid Arteries/pathology • Female •
Humans • Image Processing, Computer-Assisted/methods
• *Individuality • Magnetic Resonance
Imaging/methods • Male • Middle Aged •
Oxygen/blood • Risk Factors • Statistics as Topic
• Tunica Media/*pathology • Ultrasonography},
Abstract = {<h4>Background</h4>Cardiovascular disease (CVD) is a major
source of medical comorbidity for patients with mood and
anxiety disorders, and it remains the leading public health
burden for the general population in industrialized nations.
Indirect neurobiological evidence suggests that preclinical
risk for atherosclerosis, the main contributor to CVD, may
be conferred by interindividual variation in the
functionality of the amygdala, a brain system jointly
involved in processing behaviorally salient stimuli and
regulating the cardiovascular system.<h4>Methods</h4>In a
neuroimaging study of 36 middle-aged adults (18 women) who
were screened for confounding clinical cardiovascular and
psychiatric disorders, we examined the direct covariation
between a marker of preclinical atherosclerosis, carotid
artery intima-media thickness (IMT), and interindividual
variation in amygdala reactivity and functional connectivity
assessed during the processing of behaviorally salient
stimuli (angry and fearful facial expressions).<h4>Results</h4>After
accounting for traditional CVD risk factors, a thickening of
carotid IMT across individuals covaried with greater
amygdala reactivity and a more positive functional
connectivity between the amygdala and perigenual anterior
cingulate cortex, a corticolimbic area also implicated in
behavioral salience processing and cardiovascular
regulation.<h4>Conclusions</h4>Individual differences in
amygdala reactivity and functional connectivity may reflect
facets of a novel, systems-level neural phenotype conferring
risk for atherosclerosis and CVD.},
Language = {eng},
Doi = {10.1016/j.biopsych.2008.10.007},
Key = {Gianaros2009}
}
@article{fds252001,
Author = {Zhou, Z and Zhu, G and Hariri, AR and Enoch, MA and Scott, D and Sinha, R and Virkkunen, M and Mash, DC and Lipsky, RH and Hu, XZ and Hodgkinson, CA and Xu, K and Buzas, B and Yuan, Q and Shen, PH and Ferrell, RE and Manuck, SB and Brown, SM and Hauger, RL and Stohler, CS and Zubieta, JK and Goldman,
D},
Title = {Zhou et al. reply},
Journal = {Nature},
Volume = {458},
Number = {7238},
Pages = {E7-E7},
Publisher = {Springer Nature},
Year = {2009},
Month = {April},
ISSN = {0028-0836},
Doi = {10.1038/nature07928},
Key = {fds252001}
}
@article{Munoz2009,
Author = {Gerber, AJ and Peterson, BS and Muñoz, KE and Hyde, LW and Hariri,
AR},
Title = {Imaging genetics.},
Journal = {Journal of the American Academy of Child and Adolescent
Psychiatry},
Volume = {48},
Number = {4},
Pages = {356-361},
Address = {Department of Psychology, Center for the Neural Basis of
Cognition, University of Pittsburgh, Pittsburgh, PA
15213-2593, USA.},
Year = {2009},
Month = {April},
ISSN = {0890-8567},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19318879},
Keywords = {Amygdala/metabolism • Environment • Gene
Expression/genetics • Genetic Predisposition to Disease
• Heterozygote Detection/*instrumentation • Humans
• Mental Disorders/*genetics/metabolism •
Molecular Biology/*methods • Serotonin/genetics •
Temperament},
Language = {eng},
Doi = {10.1097/chi.0b013e31819aad07},
Key = {Munoz2009}
}
@article{Drabant2009,
Author = {Drabant, EM and McRae, K and Manuck, SB and Hariri, AR and Gross,
JJ},
Title = {Individual differences in typical reappraisal use predict
amygdala and prefrontal responses.},
Journal = {Biological psychiatry},
Volume = {65},
Number = {5},
Pages = {367-373},
Address = {Department of Psychology, Stanford University, Stanford,
California 94305, USA.},
Year = {2009},
Month = {March},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18930182},
Keywords = {Adult • Amygdala/*physiology •
Emotions/*physiology • Facial Expression • Female
• Humans • *Individuality • Middle Aged
• Prefrontal Cortex/*physiology},
Abstract = {<h4>Background</h4>Participants who are instructed to use
reappraisal to downregulate negative emotion show decreased
amygdala responses and increased prefrontal responses.
However, it is not known whether individual differences in
the tendency to use reappraisal manifests in similar neural
responses when individuals are spontaneously confronted with
negative situations. Such spontaneous emotion regulation
might play an important role in normal and pathological
responses to the emotional challenges of everyday
life.<h4>Methods</h4>Fifty-six healthy women completed a
blood oxygenation-level dependent functional magnetic
resonance imaging challenge paradigm involving the
perceptual processing of emotionally negative facial
expressions. Participants also completed measures of typical
emotion regulation use, trait anxiety, and
neuroticism.<h4>Results</h4>Greater use of reappraisal in
everyday life was related to decreased amygdala activity and
increased prefrontal and parietal activity during the
processing of negative emotional facial expressions. These
associations were not attributable to variation in trait
anxiety, neuroticism, or the use of another common form of
emotion regulation, namely suppression.<h4>Conclusions</h4>These
findings suggest that, like instructed reappraisal,
individual differences in reappraisal use are associated
with decreased activation in ventral emotion generative
regions and increased activation in prefrontal control
regions in response to negative stimuli. Such individual
differences in emotion regulation might predict successful
coping with emotional challenges as well as the onset of
affective disorders.},
Language = {eng},
Doi = {10.1016/j.biopsych.2008.09.007},
Key = {Drabant2009}
}
@article{Rasetti2009,
Author = {Rasetti, R and Mattay, VS and Wiedholz, LM and Kolachana, BS and Hariri,
AR and Callicott, JH and Meyer-Lindenberg, A and Weinberger,
DR},
Title = {Evidence that altered amygdala activity in schizophrenia is
related to clinical state and not genetic
risk.},
Journal = {The American journal of psychiatry},
Volume = {166},
Number = {2},
Pages = {216-225},
Address = {Genes, Cognition, and Psychosis Program, IRP, NIMH, NIH, Rm.
4S-235, 10 Center Dr., Bethesda, MD 20892,
USA.},
Year = {2009},
Month = {February},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19074979},
Keywords = {Adult • Amygdala/*physiopathology • Anger •
Cognition Disorders/diagnosis/*genetics/*physiopathology
• Dominance, Cerebral/physiology • Facial
Expression • Fear/physiology • Female •
Genetic Predisposition to Disease/*genetics • Gyrus
Cinguli/physiopathology • Humans • *Image
Processing, Computer-Assisted • Imaging,
Three-Dimensional • *Magnetic Resonance Imaging •
Male • Memory, Short-Term • Nerve
Net/physiopathology • *Neuropsychological Tests •
Oxygen/*blood • Pattern Recognition, Visual/physiology
• Phenotype • Schizophrenia/diagnosis/*genetics/*physiopathology},
Abstract = {<h4>Objective</h4>Although amygdala dysfunction is reported
in schizophrenia, it is unknown whether this deficit
represents a heritable phenotype that is related to risk for
schizophrenia or whether it is related to disease state. The
purpose of the present study was to examine amygdala
response to threatening faces among healthy siblings of
schizophrenia patients in whom a subtler heritable deficit
might be observed.<h4>Method</h4>Participants were 34
schizophrenia patients, 29 unaffected siblings, and 20
healthy comparison subjects. Blood-oxygen-level-dependent
(BOLD) functional magnetic resonance imaging (fMRI) was
conducted during an implicit facial information processing
task. The N-back working memory task, which has been shown
to elicit prefrontal cortex abnormalities in unaffected
siblings of schizophrenia patients, was employed as a
positive experimental control.<h4>Results</h4>Schizophrenia
patients demonstrated a deficit in amygdala reactivity to
negative face stimuli and an alteration, correlated with
neuroleptic drug dosage, in the functional coupling between
the amygdala and subgenual cingulate. In contrast,
unaffected siblings showed a pattern that was not
statistically different from that of healthy comparison
subjects. During the N-back working memory task, both
schizophrenia patients and their unaffected siblings
demonstrated a pattern of inefficient prefrontal cortex
engagement, which is consistent with earlier evidence that
this pattern is related to genetic risk for
schizophrenia.<h4>Conclusions</h4>These data suggest that
the pathophysiological mechanism underlying the inability of
individuals with schizophrenia to normally engage the
amygdala in processing fearful and angry facial
representations is more likely a phenomenon related to the
disease state, specifically to treatment.},
Language = {eng},
Doi = {10.1176/appi.ajp.2008.08020261},
Key = {Rasetti2009}
}
@article{fds251971,
Author = {Hariri, AR and Weinberger, DR},
Title = {Genetics of Human Anxiety and Its Disorders},
Pages = {669-677},
Publisher = {Elsevier},
Year = {2009},
Month = {January},
Abstract = {Normal variation in human emotionality, in temperament and
risk for affective disorders, is explained to a large degree
by genetic variation. The sequencing of the human genome has
made it possible to test the role of specific genes on
measures of human emotionality, on risk for affective
disorders, and on the brain systems that appear to mediate
emotion-related phenotypes. A novel approach, called imaging
genetics, has shown that several genes that impact on brain
serotonergic signaling affect the development and function
of circuits of the limbic system involved in emotional
experience and behavior. © 2009 Published by
null.},
Doi = {10.1016/B978-008045046-9.00845-7},
Key = {fds251971}
}
@article{Forbes2009b,
Author = {Forbes, EE and Brown, SM and Kimak, M and Ferrell, RE and Manuck, SB and Hariri, AR},
Title = {Genetic variation in components of dopamine
neurotransmission impacts ventral striatal reactivity
associated with impulsivity.},
Journal = {Molecular psychiatry},
Volume = {14},
Number = {1},
Pages = {60-70},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA 15213, USA.},
Year = {2009},
Month = {January},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17893706},
Keywords = {Adult • Analysis of Variance • Basal Ganglia/blood
supply/*physiopathology • Case-Control Studies •
Catechol O-Methyltransferase/genetics •
Dopamine/*genetics/metabolism • Dopamine Plasma
Membrane Transport Proteins/genetics • Female •
Gene Frequency • Genetic Variation/*genetics •
Genotype • Humans • Image Processing,
Computer-Assisted/methods • Impulsive
Behavior/*genetics/*pathology • Magnetic Resonance
Imaging/methods • Male • Middle Aged •
Oxygen/blood • Receptors, Dopamine D3/genetics •
Receptors, Dopamine D4/genetics • Reward •
Synaptic Transmission/*genetics • Young
Adult},
Abstract = {Individual differences in traits such as impulsivity involve
high reward sensitivity and are associated with risk for
substance use disorders. The ventral striatum (VS) has been
widely implicated in reward processing, and individual
differences in its function are linked to these disorders.
Dopamine (DA) plays a critical role in reward processing and
is a potent neuromodulator of VS reactivity. Moreover,
altered DA signaling has been associated with normal and
pathological reward-related behaviors. Functional
polymorphisms in DA-related genes represent an important
source of variability in DA function that may subsequently
impact VS reactivity and associated reward-related
behaviors. Using an imaging genetics approach, we examined
the modulatory effects of common, putatively functional
DA-related polymorphisms on reward-related VS reactivity
associated with self-reported impulsivity. Genetic variants
associated with relatively increased striatal DA release
(DRD2 -141C deletion) and availability (DAT1 9-repeat), as
well as diminished inhibitory postsynaptic DA effects (DRD2
-141C deletion and DRD4 7-repeat), predicted 9-12% of the
interindividual variability in reward-related VS reactivity.
In contrast, genetic variation directly affecting DA
signaling only in the prefrontal cortex (COMT Val158Met) was
not associated with variability in VS reactivity. Our
results highlight an important role for genetic
polymorphisms affecting striatal DA neurotransmission in
mediating interindividual differences in reward-related VS
reactivity. They further suggest that altered VS reactivity
may represent a key neurobiological pathway through which
these polymorphisms contribute to variability in behavioral
impulsivity and related risk for substance use
disorders.},
Language = {eng},
Doi = {10.1038/sj.mp.4002086},
Key = {Forbes2009b}
}
@article{Forbes2009a,
Author = {Forbes, EE and Hariri, AR and Martin, SL and Silk, JS and Moyles, DL and Fisher, PM and Brown, SM and Ryan, ND and Birmaher, B and Axelson, DA and Dahl, RE},
Title = {Altered striatal activation predicting real-world positive
affect in adolescent major depressive disorder.},
Journal = {The American journal of psychiatry},
Volume = {166},
Number = {1},
Pages = {64-73},
Address = {University of Pittsburgh School of Medicine, Western
Psychiatric Institute and Clinic, 3811 O'Hara St., Loeffler
319, Pittsburgh, PA 15213, USA. forbese@upmc.edu},
Year = {2009},
Month = {January},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19047324},
Keywords = {Adolescent • Affect/*physiology • Age Factors
• Caudate Nucleus/physiopathology • Child •
Computers, Handheld • Corpus Striatum/*physiopathology
• Depressive Disorder, Major/diagnosis/*physiopathology/psychology
• Dominance, Cerebral/physiology • Female •
Humans • *Image Processing, Computer-Assisted •
*Magnetic Resonance Imaging • Male • Motivation
• Neurons/physiology • Oxygen/*blood •
Prefrontal Cortex/physiopathology • Prognosis •
Reward • *Social Environment},
Abstract = {<h4>Objective</h4>Alterations in reward-related brain
function and phenomenological aspects of positive affect are
increasingly examined in the development of major depressive
disorder. The authors tested differences in reward-related
brain function in healthy and depressed adolescents, and the
authors examined direct links between reward-related brain
function and positive mood that occurred in real-world
contexts.<h4>Method</h4>Fifteen adolescents with major
depressive disorder and 28 adolescents with no history of
psychiatric disorder, ages 8-17 years, completed a
functional magnetic resonance imaging guessing task
involving monetary reward. Participants also reported their
subjective positive affect in natural environments during a
4-day cell-phone-based ecological momentary
assessment.<h4>Results</h4>Adolescents with major depressive
disorder exhibited less striatal response than healthy
comparison adolescents during reward anticipation and reward
outcome, but more response in dorsolateral and medial
prefrontal cortex. Diminished activation in a caudate region
associated with this depression group difference was
correlated with lower subjective positive affect in natural
environments, particularly within the depressed
group.<h4>Conclusions</h4>Results support models of altered
reward processing and related positive affect in young
people with major depressive disorder and indicate that
depressed adolescents' brain response to monetary reward is
related to their affective experience in natural
environments. Additionally, these results suggest that
reward-processing paradigms capture brain function relevant
to real-world positive affect.},
Language = {eng},
Doi = {10.1176/appi.ajp.2008.07081336},
Key = {Forbes2009a}
}
@article{Fakra2009,
Author = {Fakra, E and Hyde, LW and Gorka, A and Fisher, PM and Muñoz, KE and Kimak,
M and Halder, I and Ferrell, RE and Manuck, SB and Hariri,
AR},
Title = {Effects of HTR1A C(-1019)G on amygdala reactivity and trait
anxiety.},
Journal = {Archives of general psychiatry},
Volume = {66},
Number = {1},
Pages = {33-40},
Address = {Hopital de laTimone, ServiceHospitalo-Universitaire
dePsychiatrie, Hopital SteMarguerite, Marseille,
France.},
Year = {2009},
Month = {January},
ISSN = {0003-990X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19124686},
Keywords = {Adult • *Alleles • Amygdala/*physiopathology
• Anger/physiology • Anxiety Disorders/*genetics/physiopathology
• Arousal/*genetics/physiology •
Attention/physiology • Autoreceptors/*genetics •
Dominance, Cerebral/physiology • Facial Expression
• Fear/physiology • Female • Genotype •
Humans • *Image Processing, Computer-Assisted •
*Magnetic Resonance Imaging • Male • Middle Aged
• Oxygen/*blood • Pattern Recognition,
Visual/physiology • Receptor, Serotonin,
5-HT1A/*genetics • Signal Transduction/genetics},
Abstract = {<h4>Context</h4>Serotonin 1A (5-hydroxytryptamine 1A
[5-HT(1A)]) autoreceptors mediate negative feedback
inhibition of serotonergic neurons and play a critical role
in regulating serotonin signaling involved in shaping the
functional response of major forebrain targets, such as the
amygdala, supporting complex behavioral processes. A common
functional variation (C[-1019]G) in the human 5-HT(1A) gene
(HTR1A) represents 1 potential source of such
interindividual variability. Both in vitro and in vivo,
-1019G blocks transcriptional repression, leading to
increased autoreceptor expression. Thus, -1019G may
contribute to relatively decreased serotonin signaling at
postsynaptic forebrain target sites via increased negative
feedback.<h4>Objectives</h4>To evaluate the effects of HTR1A
C(-1019)G on amygdala reactivity and to use path analyses to
explore the impact of HTR1A-mediated variability in amygdala
reactivity on individual differences in trait anxiety. We
hypothesized that -1019G, which potentially results in
decreased serotonin signaling, would be associated with
relatively decreased amygdala reactivity and related trait
anxiety.<h4>Design</h4>Imaging genetics in participants from
an archival database.<h4>Participants</h4>Eighty-nine
healthy adults.<h4>Results</h4>Consistent with prior
findings, -1019G was associated with significantly decreased
threat-related amygdala reactivity. Importantly, this effect
was independent of that associated with another common
functional polymorphism that affects serotonin signaling,
5-HTTLPR. While there were no direct genotype effects on
trait anxiety, HTR1A C(-1019)G indirectly predicted 9.2% of
interindividual variability in trait anxiety through its
effects on amygdala reactivity.<h4>Conclusions</h4>Our
findings further implicate relatively increased serotonin
signaling, associated with a genetic variation that mediates
increased 5-HT(1A) autoreceptors, in driving amygdala
reactivity and trait anxiety. Moreover, they provide
empirical documentation of the basic premise that genetic
variation indirectly affects emergent behavioral processes
related to psychiatric disease risk by biasing the response
of underlying neural circuitries.},
Language = {eng},
Doi = {10.1001/archpsyc.66.1.33},
Key = {Fakra2009}
}
@article{Hariri2009b,
Author = {Hariri, AR},
Title = {The neurobiology of individual differences in complex
behavioral traits.},
Journal = {Annual review of neuroscience},
Volume = {32},
Pages = {225-247},
Address = {Department of Psychology and Neuroscience, Institute for
Genome Sciences and Policy, Duke University, Durham, North
Carolina 27708, USA. ah154@duke.edu},
Year = {2009},
Month = {January},
ISSN = {0147-006X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19400720},
Keywords = {Animals • Behavior/*physiology • Biological
Markers/analysis • Brain Mapping/*methods •
Genetic Predisposition to Disease/genetics • Genetic
Variation/physiology • Humans • Magnetic Resonance
Imaging/*methods • Neuropsychology/*methods •
Positron-Emission Tomography/*methods • *Quantitative
Trait, Heritable},
Abstract = {Neuroimaging, especially BOLD fMRI, has begun to identify
how variability in brain function contributes to individual
differences in complex behavioral traits. In parallel,
pharmacological fMRI and multimodal PET/fMRI are identifying
how variability in molecular signaling pathways influences
individual differences in brain function. Against this
background, functional genetic polymorphisms are being
utilized to understand the origins of variability in
signaling pathways as well as to model efficiently how such
emergent variability impacts behaviorally relevant brain
function. This article provides an overview of a research
strategy seeking to integrate these complementary
technologies and utilizes existing empirical data to
illustrate its effectiveness in illuminating the
neurobiology of individual differences in complex behavioral
traits. The article also discusses how such efforts can
contribute to the identification of predictive markers that
interact with environmental factors to precipitate disease
and to develop more effective and individually tailored
treatment regimes.},
Language = {eng},
Doi = {10.1146/annurev.neuro.051508.135335},
Key = {Hariri2009b}
}
@article{Kienast2008,
Author = {Kienast, T and Hariri, AR and Schlagenhauf, F and Wrase, J and Sterzer,
P and Buchholz, HG and Smolka, MN and Gründer, G and Cumming, P and Kumakura, Y and Bartenstein, P and Dolan, RJ and Heinz,
A},
Title = {Dopamine in amygdala gates limbic processing of aversive
stimuli in humans.},
Journal = {Nature neuroscience},
Volume = {11},
Number = {12},
Pages = {1381-1382},
Address = {Department of Psychiatry and Psychotherapy, Campus Charite
Mitte, Charite-University Medicine Berlin, Chariteplatz 1,
10117 Berlin, Germany.},
Year = {2008},
Month = {December},
ISSN = {1097-6256},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18978778},
Keywords = {Adult • *Affect • Amygdala/blood
supply/*metabolism/radionuclide imaging • *Brain
Mapping • Dihydroxyphenylalanine/analogs \&
derivatives/pharmacokinetics • Dopamine/*metabolism
• Fluorine Radioisotopes/pharmacokinetics • Gyrus
Cinguli/blood supply/radionuclide imaging • Humans
• Image Processing, Computer-Assisted • Limbic
System/*metabolism/radionuclide imaging • Magnetic
Resonance Imaging/methods • Male • Middle Aged
• Oxygen/blood • Positron-Emission
Tomography/methods • Psychophysics},
Abstract = {Dopamine is released under stress and modulates processing
of aversive stimuli. We found that dopamine storage capacity
in human amygdala, measured with 6-[(18)F]fluoro-L-DOPA
positron emission tomography, was positively correlated with
functional magnetic resonance imaging blood oxygen
level-dependent signal changes in amygdala and dorsal
anterior cingulate cortex that were evoked by aversive
stimuli. Furthermore, functional connectivity between these
two regions was inversely related to trait anxiety. Our
results suggest that individual dopamine storage capacity in
amygdala subserves modulation of emotional processing in
amygdala and dorsal cingulate, thereby contributing to
individual differences in anxious temperament.},
Language = {eng},
Doi = {10.1038/nn.2222},
Key = {Kienast2008}
}
@article{Zanardi2008,
Author = {Zanardi, R and Barbini, B and Rossini, D and Bernasconi, A and Fregni,
F and Padberg, F and Rossi, S and Wirz-Justice, A and Terman, M and Martiny, K and Bersani, G and Hariri, AR and Pezawas, L and Roiser, JP and Bertolino, A and Calabrese, G and Magri, L and Benedetti, F and Pontiggia, A and Malaguti, A and Smeraldi, E and Colombo,
C},
Title = {New perspectives on techniques for the clinical
psychiatrist: Brain stimulation, chronobiology and
psychiatric brain imaging.},
Journal = {Psychiatry and clinical neurosciences},
Volume = {62},
Number = {6},
Pages = {627-637},
Address = {San Raffaele Hospital Department of Psychiatry, Vita-Salute
University, Milan, Italy. zanardi.raffaella@hsr.it},
Year = {2008},
Month = {December},
ISSN = {1323-1316},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19067998},
Keywords = {Brain/*pathology • Diagnostic Imaging • Humans
• Magnetic Resonance Imaging • Magnetic Resonance
Spectroscopy • Mental Disorders/pathology/physiopathology/*therapy
• Mood Disorders/psychology • Periodicity •
Psychiatry/*methods/*trends • Tomography,
Emission-Computed, Single-Photon • *Transcranial
Magnetic Stimulation},
Abstract = {This review summarizes a scientific dialogue between
representatives in non-pharmacological treatment options of
affective disorders. Among the recently introduced somatic
treatments for depression those with most evidenced efficacy
will be discussed. The first part of this article presents
current opinions about the clinical applications of
transcranial magnetic stimulation in the treatment of
depression. The second part explains the most relevant uses
of chronobiology in mood disorders, while the last part
deals with the main perspectives on brain imaging techniques
in psychiatry. The aim was to bridge gaps between the
research evidence and clinical decisions, and reach an
agreement on several key points of chronobiological and
brain stimulation techniques, as well as on relevant
objectives for future research.},
Language = {eng},
Doi = {10.1111/j.1440-1819.2008.01863.x},
Key = {Zanardi2008}
}
@article{Bigos2008,
Author = {Bigos, KL and Pollock, BG and Aizenstein, HJ and Fisher, PM and Bies,
RR and Hariri, AR},
Title = {Acute 5-HT reuptake blockade potentiates human amygdala
reactivity.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {33},
Number = {13},
Pages = {3221-3225},
Address = {Department of Pharmaceutical Sciences, University of
Pittsburgh, PA, USA. bigosk@mail.nih.gov},
Year = {2008},
Month = {December},
ISSN = {0893-133X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18463627},
Keywords = {Adult • Akathisia, Drug-Induced/metabolism/physiopathology
• Amygdala/*drug effects/*metabolism •
Anxiety/chemically induced/metabolism/physiopathology •
Brain Chemistry/*drug effects/*physiology •
Citalopram/*pharmacology • Cross-Over Studies •
Depressive Disorder/drug therapy/metabolism/physiopathology
• Dose-Response Relationship, Drug • Double-Blind
Method • Facial Expression • Humans • Male
• Middle Aged • Neuropsychological Tests •
Photic Stimulation • Presynaptic Terminals/drug
effects/metabolism • Serotonin/*metabolism •
Serotonin Uptake Inhibitors/pharmacology • Young
Adult},
Abstract = {Variability in serotonin (5-HT) function is associated with
individual differences in normal mood and temperament, as
well as psychiatric illnesses, all of which are influenced
by amygdala function. This study evaluated the acute effects
of 5-HT reuptake blockade on amygdala function using
pharmacological functional MRI. Eight healthy men completed
a double-blind balanced crossover study with the selective
5-HT reuptake inhibitor, citalopram (20 mg infused over 30
min), and normal saline. Amygdala reactivity in response to
novel facial expressions was assessed on three successive
scans, once before drug/placebo infusion, once early in the
infusion, and once at the end of infusion. Acute citalopram
administration resulted in concentration-dependent increases
in human amygdala reactivity to salient stimuli. The current
pattern of 5-HT-mediated amygdala reactivity may represent
an important pathway through which SSRIs achieve an
antidepressant effect. Intriguingly, our data may also
reveal a mechanism contributing to clinical observations of
extreme agitation, restlessness, and suicidal ideation in
some individuals during acute SSRI treatment. Developing a
comprehensive model of how 5-HT modulates human amygdala
reactivity supporting behavioral and physiological arousal
will be instrumental for our understanding of basic
neurobehavioral processes, their dysfunction in psychiatric
illnesses, and their contribution to mechanism of treatment
response.},
Language = {eng},
Doi = {10.1038/npp.2008.52},
Key = {Bigos2008}
}
@misc{fds366149,
Author = {Hariri, AR},
Title = {Imaging Genetics: Integration of Neuroimaging and Genetics
in the Search for Predictive Markers},
Pages = {532-537},
Booktitle = {Genomic and Personalized Medicine: V1-2},
Year = {2008},
Month = {November},
ISBN = {9780123694201},
Doi = {10.1016/B978-0-12-369420-1.00047-0},
Key = {fds366149}
}
@article{Ousdal2008,
Author = {Ousdal, OT and Jensen, J and Server, A and Hariri, AR and Nakstad, PH and Andreassen, OA},
Title = {The human amygdala is involved in general behavioral
relevance detection: evidence from an event-related
functional magnetic resonance imaging Go-NoGo
task.},
Journal = {Neuroscience},
Volume = {156},
Number = {3},
Pages = {450-455},
Address = {TOP Project, Psychosis Research Section, Division of
Psychiatry, Building 49, Ulleval University Hospital, Oslo,
Norway.},
Year = {2008},
Month = {October},
ISSN = {0306-4522},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18775476},
Keywords = {Adult • Amygdala/*blood supply/*physiology •
Decision Making/*physiology • Female • Humans
• Image Processing, Computer-Assisted • *Magnetic
Resonance Imaging • Male • Neuropsychological
Tests • Oxygen/blood • Pattern Recognition, Visual
• Photic Stimulation/methods • Reaction
Time/physiology • Signal Detection,
Psychological/*physiology • Young Adult},
Abstract = {The amygdala is classically regarded as a detector of
potential threat and as a critical component of the neural
circuitry mediating conditioned fear responses. However, it
has been reported that the human amygdala responds to
multiple expressions of emotions as well as emotionally
neutral stimuli of a novel, uncertain or ambiguous nature.
Thus, it has been proposed that the function of the amygdala
may be of a more general art, i.e. as a detector of
behaviorally relevant stimuli [Sander D, Grafman J, Zalla T
(2003) The human amygdala: an evolved system for relevance
detection. Rev Neurosci 14:303-316]. To investigate this
putative function of the amygdala, we used event related
functional magnetic resonance imaging (fMRI) and a modified
Go-NoGo task composed of behaviorally relevant and
irrelevant letter and number stimuli. Analyses revealed
bilateral amygdala activation in response to letter stimuli
that were behaviorally relevant as compared with letters
with less behavioral relevance. Similar results were
obtained for relatively infrequent NoGo relevant stimuli as
compared with more frequent Go stimuli. Our findings support
a role for the human amygdala in general detection of
behaviorally relevant stimuli.},
Language = {eng},
Doi = {10.1016/j.neuroscience.2008.07.066},
Key = {Ousdal2008}
}
@article{Marsland2008,
Author = {Marsland, AL and Gianaros, PJ and Abramowitch, SM and Manuck, SB and Hariri, AR},
Title = {Interleukin-6 covaries inversely with hippocampal grey
matter volume in middle-aged adults.},
Journal = {Biological psychiatry},
Volume = {64},
Number = {6},
Pages = {484-490},
Address = {Behavioral Immunology Laboratory, University of Pittsburgh,
PA 15260, USA. marsland@pitt.edu},
Year = {2008},
Month = {September},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18514163},
Keywords = {Adipose Tissue/metabolism • Adult • Cognition
Disorders/diagnosis/epidemiology • Diagnostic and
Statistical Manual of Mental Disorders • Female •
Hippocampus/*anatomy \& histology/*metabolism • Humans
• Hypertension/epidemiology/metabolism •
Inflammation/epidemiology/metabolism •
Interleukin-6/*metabolism • Magnetic Resonance Imaging
• Male • Middle Aged • Nerve Net/metabolism
• Registries • Severity of Illness Index •
Wechsler Scales},
Abstract = {<h4>Background</h4>Converging animal findings suggest that
higher peripheral levels of inflammation are associated with
activation of central inflammatory mechanisms that result in
hippocampal neurodegeneration and related impairment of
memory function. We have recently shown, consistent with
animal findings, an inverse association between peripheral
levels of interleukin-6 (IL-6), a relatively stable marker
of systemic inflammation, and memory function in mid-life
adults. In the current study, we extend this work to test
whether systemic inflammation is associated with reduced
grey matter volume of the hippocampus.<h4>Methods</h4>For
this purpose, we used a computational structural
neuroimaging method (optimized voxel-based morphometry) to
evaluate the relationship between plasma IL-6 levels and
hippocampal grey matter volume in a sample of 76 relatively
healthy community volunteers ages 30-54.<h4>Results</h4>Peripheral
levels of IL-6 covaried inversely with hippocampal grey
matter volume, and this relationship persisted after
accounting for several possible confounders, including age,
gender, race, years of education, percent body fat, blood
pressure, smoking, physical activity, hours of sleep,
alcohol use, and total grey matter volume.<h4>Conclusions</h4>To
our knowledge, this is the first report of a relationship
between a peripheral marker of IL-6 and hippocampal grey
matter volume, raising the possibility that low-grade
systemic inflammation could plausibly presage subclinical
cognitive decline in part via structural neural
pathways.},
Language = {eng},
Doi = {10.1016/j.biopsych.2008.04.016},
Key = {Marsland2008}
}
@article{fds252000,
Author = {Pezawas, L and Meyer-Lindenberg, A and Goldman, AL and Verchinski,
BA and Chen, G and Kolachana, BS and Egan, MF and Mattay, VS and Hariri,
AR and Weinberger, DR},
Title = {MET BDNF protects against morphological S allele effects of
5-HTTLPR},
Journal = {Molecular Psychiatry},
Volume = {13},
Number = {7},
Pages = {654},
Publisher = {Springer Nature},
Year = {2008},
Month = {July},
ISSN = {1359-4184},
Doi = {10.1038/mp.2008.61},
Key = {fds252000}
}
@article{Pezawas2008,
Author = {Pezawas, L and Meyer-Lindenberg, A and Goldman, AL and Verchinski,
BA and Chen, G and Kolachana, BS and Egan, MF and Mattay, VS and Hariri,
AR and Weinberger, DR},
Title = {Evidence of biologic epistasis between BDNF and SLC6A4 and
implications for depression.},
Journal = {Molecular psychiatry},
Volume = {13},
Number = {7},
Pages = {709-716},
Address = {Genes, Cognition and Psychosis Program, National Institute
of Mental Health, National Institutes of Health, Bethesda,
MD 20892, USA.},
Year = {2008},
Month = {July},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18347599},
Keywords = {Amino Acid Substitution • Brain/pathology •
Brain-Derived Neurotrophic Factor/*genetics •
Depression/*genetics/pathology • Depressive
Disorder/*genetics/pathology • *Epistasis, Genetic
• European Continental Ancestry Group/genetics •
Gyrus Cinguli/pathology • Humans • Magnetic
Resonance Imaging • Polymorphism, Genetic •
Reference Values • Serotonin Plasma Membrane Transport
Proteins/*genetics},
Abstract = {Complex genetic disorders such as depression likely exhibit
epistasis, but neural mechanisms of such gene-gene
interactions are incompletely understood. 5-HTTLPR and BDNF
VAL66MET, functional polymorphisms of the serotonin (5-HT)
transporter (SLC6A4) and brain-derived neurotrophic factor
(BDNF) gene, impact on two distinct, but interacting
signaling systems, which have been related to depression and
to the modulation of neurogenesis and plasticity of
circuitries of emotion processing. Recent clinical studies
suggest that the BDNF MET allele, which shows abnormal
intracellular trafficking and regulated secretion, has a
protective effect regarding the development of depression
and in mice of social defeat stress. Here we show, using
anatomical neuroimaging techniques in a sample of healthy
subjects (n=111), that the BDNF MET allele, which is
predicted to have reduced responsivity to 5-HT signaling,
protects against 5-HTTLPR S allele-induced effects on a
brain circuitry encompassing the amygdala and the subgenual
portion of the anterior cingulate (rAC). Our analyses
revealed no effect of the 5-HTTLPR S allele on rAC volume in
the presence of BDNF MET alleles, whereas a significant
volume reduction (P<0.001) was seen on BDNF VAL/VAL
background. Interacting genotype effects were also found in
structural connectivity between amygdala and rAC (P=0.002).
These data provide in vivo evidence of biologic epistasis
between SLC6A4 and BDNF in the human brain by identifying a
neural mechanism linking serotonergic and neurotrophic
signaling on the neural systems level, and have implications
for personalized treatment planning in depression.},
Language = {eng},
Doi = {10.1038/mp.2008.32},
Key = {Pezawas2008}
}
@article{Gianaros2008b,
Author = {Gianaros, PJ and Horenstein, JA and Hariri, AR and Sheu, LK and Manuck,
SB and Matthews, KA and Cohen, S},
Title = {Potential neural embedding of parental social
standing.},
Journal = {Social cognitive and affective neuroscience},
Volume = {3},
Number = {2},
Pages = {91-96},
Address = {Department of Psychiatry, University of Pittsburgh, 3811
O'Hara Street, Pittsburgh, PA 15213, USA.
gianarospj@upmc.edu},
Year = {2008},
Month = {June},
ISSN = {1749-5016},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18594696},
Keywords = {Adaptation, Psychological/physiology •
Aggression/*physiology/psychology •
Amygdala/*physiology • Facial Expression •
Hierarchy, Social • Humans • Magnetic Resonance
Imaging • Male • Parents/psychology •
Reference Values • Self Concept • *Social Class
• *Social Perception • Stress,
Psychological/*physiopathology • Young
Adult},
Abstract = {Socioeconomic disadvantage during childhood and adolescence
predicts poor mental and physical health and premature death
by major medical diseases in adulthood. However, the neural
pathways through which socioeconomic factors may exert a
developmental influence on health and longevity remain
largely unknown. This fMRI study provides novel evidence of
a unique relationship between the perception that one's
parents had a relatively low social standing--a putative
indicator of early socioeconomic disadvantage--and greater
amygdala reactivity to threatening facial expressions. This
relationship was not explained by several possible
confounders, including sex, ethnicity, dispositional
emotionality, symptoms of depression and anxiety, parental
education and participants' perceptions of their own social
standing. The amygdala expresses marked developmental
plasticity and plays instrumental roles in processing
emotional information, regulating emotion-related behaviors
and orchestrating biobehavioral stress responses throughout
life. Thus, these findings may provide insight into the
neurodevelopmental pathways impacting socioeconomic
disparities in health.},
Language = {eng},
Doi = {10.1093/scan/nsn003},
Key = {Gianaros2008b}
}
@article{Fisher2008,
Author = {Fisher, PM and Muñoz, KE and Hariri, AR},
Title = {Identification of neurogenetic pathways of risk for
psychopathology.},
Journal = {American journal of medical genetics. Part C, Seminars in
medical genetics},
Volume = {148C},
Number = {2},
Pages = {147-153},
Address = {University of Pittsburgh, Pittsburgh, PA 15213-2593,
USA.},
Year = {2008},
Month = {May},
ISSN = {1552-4868},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18412103},
Keywords = {Brain/growth \& development/*physiopathology • Catechol
O-Methyltransferase/genetics/physiology • Diagnostic
Imaging • Dopamine Plasma Membrane Transport
Proteins/genetics/physiology • Female • Humans
• Male • Mental Disorders/diagnosis/*genetics/*physiopathology
• Monoamine Oxidase/genetics/physiology •
Psychopathology • Risk Factors • Serotonin Plasma
Membrane Transport Proteins/genetics/physiology •
Tryptophan Hydroxylase/genetics/physiology},
Abstract = {Imaging genetics has been a highly effective and
increasingly applied strategy for identifying the impact of
genetic polymorphisms on individual differences in neural
circuitry supporting complex behaviors. The application of
imaging genetics towards further elucidating neural
circuitry associated with the pathophysiology of psychiatric
illness is of particular interest given its potential to
guide the development and improvement of current therapeutic
methods. The identification of genetic variants that
contribute to or predict the disruption of specific neural
pathways associated with psychopathology may also serve as
useful markers of risk demarcating individuals with elevated
susceptibility for psychiatric illness and affording early
or even preemptive treatment strategies. In the continued
development of this technique, recent multimodal
neuroimaging strategies and studies examining the effects of
multiple genes in concert within large subject populations
have shown promise in the development of a more complete
understanding of the interrelationships between genes, brain
function, behavior and associated risk for
psychopathology.},
Language = {eng},
Doi = {10.1002/ajmg.c.30173},
Key = {Fisher2008}
}
@article{Munafo2008,
Author = {Munafò, MR and Brown, SM and Hariri, AR},
Title = {Serotonin transporter (5-HTTLPR) genotype and amygdala
activation: a meta-analysis.},
Journal = {Biological psychiatry},
Volume = {63},
Number = {9},
Pages = {852-857},
Address = {Department of Experimental Psychology, University of
Bristol, United Kingdom. marcus.munafo@bristol.ac.uk},
Year = {2008},
Month = {May},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17949693},
Keywords = {Adolescent • Adult • Alleles •
Amygdala/*physiopathology • Anxiety
Disorders/genetics/physiopathology • Depressive
Disorder/genetics/physiopathology • Female •
*Genotype • Humans • Individuality • Magnetic
Resonance Imaging • Male • Phenotype •
Polymorphism, Genetic/*genetics • Promoter Regions,
Genetic/*genetics • Serotonin Plasma Membrane Transport
Proteins/*genetics • Stress, Psychological/complications},
Abstract = {<h4>Background</h4>We evaluated the magnitude of the
reported associations between amygdala activation and the
serotonin transporter gene linked polymorphic region
(5-HTTLPR) and the likely effect size of this
relationship.<h4>Methods</h4>We used meta-analytic
techniques to combine data from existing published and
unpublished studies. We also tested for possible publication
bias and explored possible moderating influences on any
association, such as sample ancestry.<h4>Results</h4>Our
results provide support for the association of the 5-HTTLPR
polymorphism and amygdala activation and suggest that this
locus may account for up to 10% of phenotypic variance.
Although we did not observe evidence for potential
publication bias in our main analysis, this was due in part
to efforts to obtain unpublished data pertinent to this
meta-analysis, and when three unpublished data sets were
excluded we did observe evidence of such bias. We also
observed evidence that the first published study may provide
an overestimate of the true effect size, which is consistent
with findings from genetic association studies of other
phenotypes.<h4>Conclusions</h4>Although our analysis
provides support for the association of the 5-HTTLPR
polymorphism and amygdala activation, it also suggests that
most studies to date are nevertheless lacking in statistical
power. Increasing the sample sizes of future imaging
genetics studies will allow a more accurate characterization
of any true effect size and afford adequate power to examine
the impact of multiple polymorphisms that likely work in
concert to affect gene function and, in turn, bias neural
processes mediating dispositional traits such as temperament
and personality.},
Language = {eng},
Doi = {10.1016/j.biopsych.2007.08.016},
Key = {Munafo2008}
}
@article{Krystal2008,
Author = {Krystal, JH and Carter, CS and Geschwind, D and Manji, HK and March, JS and Nestler, EJ and Zubieta, J-K and Charney, DS and Goldman, D and Gur, RE and Lieberman, JA and Roy-Byrne, P and Rubinow, DR and Anderson, SA and Barondes, S and Berman, KF and Blair, J and Braff, DL and Brown, ES and Calabrese, JR and Carlezon, WA and Cook, EH and Davidson, RJ and Davis,
M and Desimone, R and Drevets, WC and Duman, RS and Essock, SM and Faraone,
SV and Freedman, R and Friston, KJ and Gelernter, J and Geller, B and Gill,
M and Gould, E and Grace, AA and Grillon, C and Gueorguieva, R and Hariri,
AR and Innis, RB and Jones, EG and Kleinman, JE and Koob, GF and Krystal,
AD and Leibenluft, E and Levinson, DF and Levitt, PR and Lewis, DA and Liberzon, I and Lipska, BK and Marder, SR and Markou, A and Mason, GF and McDougle, CJ and McEwen, BS and McMahon, FJ and Meaney, MJ and Meltzer,
HY and Merikangas, KR and Meyer-Lindenberg, A and Mirnics, K and Monteggia, LM and Neumeister, A and O'Brien, CP and Owen, MJ and Pine,
DS and Rapoport, JL and Rauch, SL and Robbins, TW and Rosenbaum, JF and Rosenberg, DR and Ross, CA and Rush, AJ and Sackeim, HA and Sanacora, G and Schatzberg, AF and Shaham, Y and Siever, LJ and Sunderland, T and Tecott, LH and Thase, ME and Todd, RD and Weissman, MM and Yehuda, R and Yoshikawa, T and Young, EA and McCandless, R},
Title = {It is time to take a stand for medical research and against
terrorism targeting medical scientists.},
Journal = {Biol Psychiatry},
Volume = {63},
Number = {8},
Pages = {725-727},
Address = {Department of Psychiatry, Yale University School of
Medicine, New Haven, Connecticut, USA. john.krystal@yale.edu},
Year = {2008},
Month = {April},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18371494},
Keywords = {*Animal Experimentation • Animal Rights • Animals
• *Attitude of Health Personnel • *Biomedical
Research • Crime/prevention \& control • Ethics,
Research • Humans • Primates • *Research
Personnel • Terrorism/*prevention \& control •
United States},
Language = {eng},
Doi = {10.1016/j.biopsych.2008.03.005},
Key = {Krystal2008}
}
@article{Zhou2008,
Author = {Zhou, Z and Zhu, G and Hariri, AR and Enoch, M-A and Scott, D and Sinha, R and Virkkunen, M and Mash, DC and Lipsky, RH and Hu, X-Z and Hodgkinson, CA and Xu, K and Buzas, B and Yuan, Q and Shen, P-H and Ferrell, RE and Manuck,
SB and Brown, SM and Hauger, RL and Stohler, CS and Zubieta, J-K and Goldman, D},
Title = {Genetic variation in human NPY expression affects stress
response and emotion.},
Journal = {Nature},
Volume = {452},
Number = {7190},
Pages = {997-1001},
Address = {Laboratory of Neurogenetics, NIAAA, NIH, Bethesda, Maryland
20892, USA.},
Year = {2008},
Month = {April},
ISSN = {0028-0836},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18385673},
Keywords = {Alleles • Anxiety/genetics • Anxiety
Disorders/genetics • Brain/*metabolism/physiology/physiopathology
• *Emotions • European Continental Ancestry
Group/genetics • Facial Expression •
Finland/ethnology • Gene Expression
Regulation/*genetics • Genetic Variation/*genetics
• Haplotypes/genetics • Humans •
Lymphocytes/metabolism • Magnetic Resonance Imaging
• Male • Neuropeptide Y/blood/*genetics •
Opioid Peptides/metabolism • Pain/genetics •
Polymorphism, Single Nucleotide/genetics • RNA,
Messenger/genetics/metabolism • Stress,
Physiological/*genetics/psychology • United
States/ethnology},
Abstract = {Understanding inter-individual differences in stress
response requires the explanation of genetic influences at
multiple phenotypic levels, including complex behaviours and
the metabolic responses of brain regions to emotional
stimuli. Neuropeptide Y (NPY) is anxiolytic and its release
is induced by stress. NPY is abundantly expressed in regions
of the limbic system that are implicated in arousal and in
the assignment of emotional valences to stimuli and
memories. Here we show that haplotype-driven NPY expression
predicts brain responses to emotional and stress challenges
and also inversely correlates with trait anxiety. NPY
haplotypes predicted levels of NPY messenger RNA in
post-mortem brain and lymphoblasts, and levels of plasma
NPY. Lower haplotype-driven NPY expression predicted higher
emotion-induced activation of the amygdala, as well as
diminished resiliency as assessed by pain/stress-induced
activations of endogenous opioid neurotransmission in
various brain regions. A single nucleotide polymorphism (SNP
rs16147) located in the promoter region alters NPY
expression in vitro and seems to account for more than half
of the variation in expression in vivo. These convergent
findings are consistent with the function of NPY as an
anxiolytic peptide and help to explain inter-individual
variation in resiliency to stress, a risk factor for many
diseases.},
Language = {eng},
Doi = {10.1038/nature06858},
Key = {Zhou2008}
}
@article{Fakra2008,
Author = {Fakra, E and Salgado-Pineda, P and Delaveau, P and Hariri, AR and Blin,
O},
Title = {Neural bases of different cognitive strategies for facial
affect processing in schizophrenia.},
Journal = {Schizophrenia research},
Volume = {100},
Number = {1-3},
Pages = {191-205},
Address = {CIC-UPCET, Hopital de la Timone, UMR CNRS 6193 INCM,
Marseille, France. eric.fakra@ap-hm.fr},
Year = {2008},
Month = {March},
ISSN = {0920-9964},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18234477},
Keywords = {Adult • Affect/*physiology • Amygdala/physiopathology
• Brain/*physiopathology • Brain Mapping •
Cerebral Cortex/physiopathology • Control Groups •
*Facial Expression • Female • Functional
Laterality/physiology • Humans • Limbic
System/physiopathology • Magnetic Resonance
Imaging/*statistics \& numerical data • Male •
Models, Neurological • Neural Pathways/physiopathology
• Recognition (Psychology)/physiology •
Schizophrenia/*diagnosis/physiopathology •
*Schizophrenic Psychology • Social Perception •
Task Performance and Analysis • Visual
Perception/*physiology},
Abstract = {<h4>Objective</h4>To examine the neural basis and dynamics
of facial affect processing in schizophrenic patients as
compared to healthy controls.<h4>Method</h4>Fourteen
schizophrenic patients and fourteen matched controls
performed a facial affect identification task during fMRI
acquisition. The emotional task included an intuitive
emotional condition (matching emotional faces) and a more
cognitively demanding condition (labeling emotional faces).
Individual analysis for each emotional condition, and
second-level t-tests examining both within-, and
between-group differences, were carried out using a random
effects approach. Psychophysiological interactions (PPI)
were tested for variations in functional connectivity
between amygdala and other brain regions as a function of
changes in experimental conditions (labeling versus
matching).<h4>Results</h4>During the labeling condition,
both groups engaged similar networks. During the matching
condition, schizophrenics failed to activate regions of the
limbic system implicated in the automatic processing of
emotions. PPI revealed an inverse functional connectivity
between prefrontal regions and the left amygdala in healthy
volunteers but there was no such change in patients.
Furthermore, during the matching condition, and compared to
controls, patients showed decreased activation of regions
involved in holistic face processing (fusiform gyrus) and
increased activation of regions associated with feature
analysis (inferior parietal cortex, left middle temporal
lobe, right precuneus).<h4>Conclusions</h4>Our findings
suggest that schizophrenic patients invariably adopt a
cognitive approach when identifying facial affect. The
distributed neocortical network observed during the
intuitive condition indicates that patients may resort to
feature-based, rather than configuration-based, processing
and may constitute a compensatory strategy for limbic
dysfunction.},
Language = {eng},
Doi = {10.1016/j.schres.2007.11.040},
Key = {Fakra2008}
}
@article{Buckholtz2008,
Author = {Buckholtz, JW and Callicott, JH and Kolachana, B and Hariri, AR and Goldberg, TE and Genderson, M and Egan, MF and Mattay, VS and Weinberger, DR and Meyer-Lindenberg, A},
Title = {Genetic variation in MAOA modulates ventromedial prefrontal
circuitry mediating individual differences in human
personality.},
Journal = {Molecular psychiatry},
Volume = {13},
Number = {3},
Pages = {313-324},
Address = {Neuroimaging Core Facility, National Institute for Mental
Health, NIH, DHHS, Bethesda, MD 20892-1365,
USA.},
Year = {2008},
Month = {March},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17519928},
Keywords = {Adult • Brain Mapping • Facial Expression •
Female • *Genetic Variation • Humans • Image
Processing, Computer-Assisted • *Individuality •
Magnetic Resonance Imaging • Male • Models,
Biological • Monoamine Oxidase/*genetics • Neural
Pathways/blood supply/physiology • Neuropsychological
Tests • Oxygen/blood • Personality/*genetics
• Photic Stimulation/methods • Prefrontal
Cortex/blood supply/*physiology},
Abstract = {Little is known about neural mechanisms underlying human
personality and temperament, despite their considerable
importance as highly heritable risk mediators for somatic
and psychiatric disorders. To identify these circuits, we
used a combined genetic and imaging approach focused on
Monoamine Oxidase A (MAOA), encoding a key enzyme for
monoamine metabolism previously associated with temperament
and antisocial behavior. Male carriers of a low-expressing
genetic variant exhibited dysregulated amygdala activation
and increased functional coupling with ventromedial
prefrontal cortex (vmPFC). Stronger coupling predicted
increased harm avoidance and decreased reward dependence
scores, suggesting that this circuitry mediates a part of
the association of MAOA with these traits. We utilized path
analysis to parse the effective connectivity within this
system, and provide evidence that vmPFC regulates amygdala
indirectly by influencing rostral cingulate cortex function.
Our data implicate a neural circuit for variation in human
personality under genetic control, provide an anatomically
consistent mechanism for vmPFC-amygdala interactions
underlying this variation, and suggest a role for vmPFC as a
superordinate regulatory area for emotional arousal and
social behavior.},
Language = {eng},
Doi = {10.1038/sj.mp.4002020},
Key = {Buckholtz2008}
}
@article{fds251999,
Author = {Hariri, AR},
Title = {Imaging genetics offers new predictive markers of individual
differences in behavior and risk for psychiatric
diseases},
Journal = {Neuropsychopharmacology},
Volume = {33},
Number = {1},
Pages = {201-202},
Publisher = {Springer Nature},
Year = {2008},
Month = {January},
ISSN = {0893-133X},
Doi = {10.1038/sj.npp.1301608},
Key = {fds251999}
}
@article{Gianaros2008a,
Author = {Gianaros, PJ and Sheu, LK and Matthews, KA and Jennings, JR and Manuck,
SB and Hariri, AR},
Title = {Individual differences in stressor-evoked blood pressure
reactivity vary with activation, volume, and functional
connectivity of the amygdala.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {28},
Number = {4},
Pages = {990-999},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15213, USA. gianarospj@upmc.edu},
Year = {2008},
Month = {January},
ISSN = {0270-6474},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18216206},
Keywords = {Adolescent • Adult • Amygdala/anatomy \&
histology/*physiology • Blood Pressure/*physiology
• Female • Humans • *Individuality •
Male • Nerve Net/anatomy \& histology/*physiology
• Organ Size/physiology • Pons/anatomy \&
histology/physiology • Stress, Psychological/*physiopathology},
Abstract = {Individuals who exhibit exaggerated blood pressure reactions
to psychological stressors are at risk for hypertension,
ventricular hypertrophy, and premature atherosclerosis;
however, the neural systems mediating exaggerated blood
pressure reactivity and associated cardiovascular risk in
humans remain poorly defined. Animal models indicate that
the amygdala orchestrates stressor-evoked blood pressure
reactions via reciprocal signaling with corticolimbic and
brainstem cardiovascular-regulatory circuits. Based on these
models, we used a multimodal neuroimaging approach to
determine whether human individual differences in
stressor-evoked blood pressure reactivity vary with amygdala
activation, gray matter volume, and functional connectivity
with corticolimbic and brainstem areas implicated in
stressor processing and cardiovascular regulation. We
monitored mean arterial pressure (MAP) and concurrent
functional magnetic resonance imaging BOLD signal changes in
healthy young individuals while they completed a Stroop
color-word stressor task, validated previously in
epidemiological studies of cardiovascular risk. Individuals
exhibiting greater stressor-evoked MAP reactivity showed (1)
greater amygdala activation, (2) lower amygdala gray matter
volume, and (3) stronger positive functional connectivity
between the amygdala and perigenual anterior cingulate
cortex and brainstem pons. Individual differences in
amygdala activation, gray matter volume, and functional
connectivity with corticolimbic and brainstem circuits may
partly underpin cardiovascular disease risk by impacting
stressor-evoked blood pressure reactivity.},
Language = {eng},
Doi = {10.1523/jneurosci.3606-07.2008},
Key = {Gianaros2008a}
}
@article{Bigos2007,
Author = {Bigos, KL and Hariri, AR},
Title = {Neuroimaging: technologies at the interface of genes, brain,
and behavior.},
Journal = {Neuroimaging clinics of North America},
Volume = {17},
Number = {4},
Pages = {459-viii},
Address = {Department of Pharmaceutical Sciences, University of
Pittsburgh School of Pharmacy, Pittsburgh, PA 15213,
USA.},
Year = {2007},
Month = {November},
ISSN = {1052-5149},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17983963},
Keywords = {Behavior/*physiology • Brain/*physiology • *Brain
Mapping • *Gene Expression • Humans •
*Polymorphism, Genetic},
Abstract = {Neuroimaging technologies provide a powerful approach to
exploring the genetic basis of individual differences in
complex behaviors and vulnerability to neuropsychiatric
illness. Functional MRI studies have established important
physiologic links between genetic polymorphisms and robust
differences in information processing within distinct brain
regions and circuits that have been linked to the
manifestation of various disease. Neuroimaging technologies
represent a critical tool in efforts to understand the
neurobiology of normal and pathologic behavioral states.
Research capitalizing on neuroimagingbased integration will
contribute to the identification of predictive markers and
biologic pathways for neuropsychiatric disease vulnerability
and the generation of novel targets for therapeutic
intervention.},
Language = {eng},
Doi = {10.1016/j.nic.2007.09.005},
Key = {Bigos2007}
}
@article{Manuck2007,
Author = {Manuck, SB and Brown, SM and Forbes, EE and Hariri,
AR},
Title = {Temporal stability of individual differences in amygdala
reactivity.},
Journal = {The American journal of psychiatry},
Volume = {164},
Number = {10},
Pages = {1613-1614},
Year = {2007},
Month = {October},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17898358},
Keywords = {Adult • Amygdala/*physiology • Anger/physiology
• Emotions/*physiology • Fear/physiology •
Female • Humans • *Individuality • Magnetic
Resonance Imaging/*statistics \& numerical data • Male
• Middle Aged • Mood Disorders/diagnosis},
Language = {eng},
Doi = {10.1176/appi.ajp.2007.07040609},
Key = {Manuck2007}
}
@article{fds251998,
Author = {Rubino, V and Blasi, G and Latorre, V and Fazio, L and d'Errico, I and Mazzola, V and Caforio, G and Nardini, M and Popolizio, T and Hariri, A and Arciero, G and Bertolino, A},
Title = {Activity in medial prefrontal cortex during cognitive
evaluation of threatening stimuli as a function of
personality style.},
Journal = {Brain research bulletin},
Volume = {74},
Number = {4},
Pages = {250-257},
Year = {2007},
Month = {September},
ISSN = {0361-9230},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17720547},
Abstract = {Cognitive evaluation of emotional stimuli involves a network
of brain regions including the medial prefrontal cortex
(mPFC). However, threatening stimuli may be perceived with
differential salience in different individuals. The goal of
our study was to evaluate how different personality styles
are associated with differential modulation of brain
activity during explicit recognition of fearful and angry
facial expressions. Twenty-eight healthy subjects underwent
fMRI. Based on a cognitivist model, subjects were
categorized according to how they attribute salience to
emotional stimuli and how they regulate their emotional
activation. We compared 14 phobic prone (PP) subjects, whose
identity is more centered on the inner experience ("inward")
and around control of environmental threat, and 14 eating
disorders prone (EDP) subjects, whose identity is more
centered on external referential contexts ("outward") and
much less around control of threatening stimuli. During fMRI
subjects either matched the identity of one of two angry and
fearful faces to that of a simultaneously presented target
face or identified the expression of a target face by
choosing one of two simultaneously presented linguistic
labels. The fMRI results indicated that PP subjects had
greater mPFC activation when compared with EDP subjects
during cognitive labeling of threatening stimuli. Activity
in the mPFC also correlated with personality style scores.
These results demonstrate that PP subjects recruit greater
neuronal resources in mPFC whose activity is associated with
cognitive aspects that are closely intertwined with
emotional processing. These findings are consistent with the
contention that cognitive evaluation and salience of
emotional stimuli are associated with different personality
styles.},
Doi = {10.1016/j.brainresbull.2007.06.019},
Key = {fds251998}
}
@article{Gianaros2007,
Author = {Gianaros, PJ and Horenstein, JA and Cohen, S and Matthews, KA and Brown,
SM and Flory, JD and Critchley, HD and Manuck, SB and Hariri,
AR},
Title = {Perigenual anterior cingulate morphology covaries with
perceived social standing.},
Journal = {Social cognitive and affective neuroscience},
Volume = {2},
Number = {3},
Pages = {161-173},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA 15213, USA. gianarospj@upmc.edu},
Year = {2007},
Month = {September},
ISSN = {1749-5016},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18418472},
Keywords = {Adult • Cognition/physiology • Female • Gyrus
Cinguli/*anatomy \& histology/physiology • Humans
• Male • Middle Aged • *Social Class •
*Social Perception},
Abstract = {Low socioeconomic status (SES) increases the risk for
developing psychiatric and chronic medical disorders. A
stress-related pathway by which low SES may affect mental
and physical health is through the perception of holding a
low social standing, termed low subjective social status.
This proposal implicates overlapping brain regions mediating
stress reactivity and socioemotional behaviors as
neuroanatomical substrates that could plausibly link
subjective social status to health-related outcomes. In a
test of this proposal, we used a computational structural
neuroimaging method (voxel-based morphometry) in a healthy
community sample to examine the relationships between
reports of subjective social status and regional gray matter
volume. Results showed that after accounting for potential
demographic confounds, subclinical depressive symptoms,
dispositional forms of negative emotionality and
conventional indicators of SES, self-reports of low
subjective social status uniquely covaried with reduced gray
matter volume in the perigenual area of the anterior
cingulate cortex (pACC)-a brain region involved in
experiencing emotions and regulating behavioral and
physiological reactivity to psychosocial stress. The pACC
may represent a neuroanatomical substrate by which perceived
social standing relates to mental and physical
health.},
Language = {eng},
Doi = {10.1093/scan/nsm013},
Key = {Gianaros2007}
}
@article{Conklin2007,
Author = {Conklin, SM and Gianaros, PJ and Brown, SM and Yao, JK and Hariri, AR and Manuck, SB and Muldoon, MF},
Title = {Long-chain omega-3 fatty acid intake is associated
positively with corticolimbic gray matter volume in healthy
adults.},
Journal = {Neuroscience letters},
Volume = {421},
Number = {3},
Pages = {209-212},
Address = {Department of Psychiatry, University of Pittsburgh, School
of Medicine, Pittsburgh, PA 15260, United States.
conklinSM@UPMC.Edu},
Year = {2007},
Month = {June},
ISSN = {0304-3940},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17574755},
Keywords = {Adult • Brain Mapping • Cerebral Cortex/anatomy \&
histology/*drug effects • Fatty Acids,
Omega-3/*administration \& dosage • Female •
Humans • Limbic System/*anatomy \& histology/*drug
effects • Magnetic Resonance Imaging/methods •
Male • Middle Aged},
Abstract = {<h4>Background</h4>In animals, dendritic arborization and
levels of brain derived neurotrophic factor are positively
associated with intake of the omega-3 fatty acids. Here, we
test whether omega-3 fatty acid intake in humans varies with
individual differences in gray matter volume, an in vivo,
systems-level index of neuronal integrity.<h4>Methods</h4>Fifty-five
healthy adults completed two 24h dietary recall interviews.
Intake of long-chain omega-3 fatty acids was categorized by
tertiles. Regional gray matter volumes in a putative
emotional brain circuitry comprised of the anterior
cingulate cortex (ACC), amygdala and hippocampus were
calculated using optimized voxel-based morphometry on
high-resolution structural magnetic resonance
images.<h4>Results</h4>Region of interest analyses revealed
positive associations between reported dietary omega-3
intake and gray matter volume in the subgenual ACC, the
right hippocampus and the right amygdala, adjusted for total
gray matter volume of brain. Unconstrained whole-brain
analyses confirmed that higher intake of omega-3 fatty acids
was selectively associated with increased greater gray
matter volume in these and not other regions.<h4>Conclusions</h4>Higher
reported consumption of the long-chain omega-3 fatty acids
is associated with greater gray matter volume in nodes of a
corticolimbic circuitry supporting emotional arousal and
regulation. Such associations may mediate previously
observed effects of omega-3 fatty acids on memory, mood and
affect regulation.},
Language = {eng},
Doi = {10.1016/j.neulet.2007.04.086},
Key = {Conklin2007}
}
@article{Heinz2007,
Author = {Heinz, A and Smolka, MN and Braus, DF and Wrase, J and Beck, A and Flor, H and Mann, K and Schumann, G and Büchel, C and Hariri, AR and Weinberger,
DR},
Title = {Serotonin transporter genotype (5-HTTLPR): effects of
neutral and undefined conditions on amygdala
activation.},
Journal = {Biological psychiatry},
Volume = {61},
Number = {8},
Pages = {1011-1014},
Address = {Department of Psychiatry, Charite University Medicine
Berlin, Campus Charite Mitte, Germany.},
Year = {2007},
Month = {April},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17157270},
Keywords = {Adult • Amygdala/blood supply/*physiology •
Emotions/*physiology • Functional Laterality •
Gene Frequency • Genotype • Humans • Image
Processing, Computer-Assisted/methods • Magnetic
Resonance Imaging/methods • Male • Middle Aged
• Oxygen/blood • Photic Stimulation •
Polymorphism, Genetic • Serotonin Plasma Membrane
Transport Proteins/*genetics},
Abstract = {<h4>Background</h4>A polymorphism of the human serotonin
transporter gene (SCL6A4) has been associated with serotonin
transporter expression and with processing of aversive
stimuli in the amygdala. Functional imaging studies show
that during the presentation of aversive versus neutral
cues, healthy carriers of the short (s) allele showed
stronger amygdala activation than long (l) carriers.
However, a recent report suggested that this interaction is
driven by amygdala deactivation during presentation of
neutral stimuli in s carriers.<h4>Methods</h4>Functional MRI
was used to assess amygdala activation during the
presentation of a fixation cross or affectively aversive or
neutral visual stimuli in 29 healthy men.<h4>Results</h4>Amygdala
activation was increased in s carriers during undefined
states such as the presentation of a fixation cross compared
with emotionally neutral conditions.<h4>Conclusions</h4>This
finding suggests that s carriers show stronger amygdala
reactivity to stimuli and contexts that are relatively
uncertain, which we propose are stressful.},
Language = {eng},
Doi = {10.1016/j.biopsych.2006.08.019},
Key = {Heinz2007}
}
@article{fds251997,
Author = {Hariri, AR and Fisher, PM},
Title = {Regulation of corticolimbic reactivity via the
5-HT1A autoreceptor in the pathophysiology and
treatment of depression},
Journal = {Future Neurology},
Volume = {2},
Number = {2},
Pages = {121-124},
Publisher = {Future Medicine Ltd},
Year = {2007},
Month = {March},
ISSN = {1479-6708},
Doi = {10.2217/14796708.2.2.121},
Key = {fds251997}
}
@article{fds251996,
Author = {Fisher, PM and Meltzer, CC and Ziolko, SK and Price, JC and Moses-Kolko,
EL and Berga, SL and Hariri, AR},
Title = {Erratum: Capacity for 5-HT1A-mediated autoregulation
predicts amygdala reactivity (Nature Neuroscience (2006) 9
(1362-1363))},
Journal = {Nature Neuroscience},
Volume = {10},
Number = {2},
Pages = {263},
Publisher = {Springer Nature},
Year = {2007},
Month = {February},
ISSN = {1097-6256},
Doi = {10.1038/nn0207-263a},
Key = {fds251996}
}
@article{Lerner2007,
Author = {Lerner, JS and Dahl, RE and Hariri, AR and Taylor,
SE},
Title = {Facial expressions of emotion reveal neuroendocrine and
cardiovascular stress responses.},
Journal = {Biological psychiatry},
Volume = {61},
Number = {2},
Pages = {253-260},
Address = {Department of Social \& Decision Sciences, Carnegie Mellon
University, Pittsburgh, PA 15213, USA. jlerner@cmu.edu},
Year = {2007},
Month = {January},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17150197},
Keywords = {Adolescent • Adult • Anger/physiology •
Arousal/*physiology • Blood Pressure/*physiology •
Emotions/*physiology • *Facial Expression • Facial
Muscles/physiology • Fear/physiology • Female
• Heart Rate/*physiology • Humans •
Hydrocortisone/*blood • Hypothalamo-Hypophyseal
System/*physiology • Male • Pituitary-Adrenal
System/*physiology • Principal Component Analysis
• Problem Solving/physiology • Stress,
Psychological/complications},
Abstract = {<h4>Background</h4>The classic conception of stress involves
undifferentiated negative affect and corresponding
biological reactivity. The present study hypothesized a new
conception, disaggregating stress into emotion-specific,
contrasting patterns of biological response. Specifically,
it hypothesized contrasting patterns for indignation
(comprised of anger and disgust) versus fear. Moreover, it
hypothesized that facial expressions of these emotions would
signal corresponding biological stress responses.<h4>Methods</h4>Ninety-two
adults engaged in annoyingly difficult stress-challenge
tasks, during which cardiovascular responses,
hypothalamic-pituitary-adrenocortical (HPA) axis responses
(i.e., cortisol), emotional expressions (i.e., facial muscle
movements), and subjective emotional experience were
assessed.<h4>Results</h4>Pronounced individual differences
emerged in specific emotional responses to the stressors.
Analyses of facial expressions revealed that the more fear
individuals displayed in response to the stressors, the
higher their cardiovascular and cortisol responses to
stress. By contrast, the more indignation individuals
displayed in response to the same stressors the lower their
cortisol levels and cardiovascular responses.<h4>Conclusions</h4>Facial
expressions of emotion signal biological responses to
stress. Fear expressions signal elevated cortisol and
cardiovascular reactivity; indignation signals attenuated
cortisol and cardiovascular reactivity, patterns that
implicate individual differences in stress appraisals.
Rather than conceptualizing stress as generalized negative
affect, studies can be informed by this emotion-specific
approach to stress responses.},
Language = {eng},
Doi = {10.1016/j.biopsych.2006.08.016},
Key = {Lerner2007}
}
@article{fds251995,
Author = {Bertolino, A and Rubino, V and Sambataro, F and Blasi, G and Latorre, V and Fazio, L and Caforio, G and Petruzzella, V and Kolachana, B and Hariri,
A and Meyer-Lindenberg, A and Nardini, M and Weinberger, DR and Scarabino, T},
Title = {Prefrontal-hippocampal coupling during memory processing is
modulated by COMT val158met genotype.},
Journal = {Biological psychiatry},
Volume = {60},
Number = {11},
Pages = {1250-1258},
Year = {2006},
Month = {December},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16950222},
Abstract = {<h4>Background</h4>Studies in humans and in animals have
demonstrated that a network of brain regions is involved in
performance of declarative and recognition memory tasks.
This network includes the hippocampal formation (HF) as well
as the ventrolateral prefrontal cortex (VLPFC). Studies in
animals have suggested that the relationship between these
brain regions is strongly modulated by dopamine.<h4>Methods</h4>Using
fMRI in healthy humans matched for a series of demographic
and genetic variables, we studied the effect of the COMT
val158met polymorphism on function of HF and VLPFC as well
as on their functional coupling during recognition
memory.<h4>Results</h4>The COMT Val allele was associated
with: relatively poorer performance at retrieval; reduced
recruitment of neuronal resources in HF and increased
recruitment in VLPFC during both encoding and retrieval; and
unfavorable functional coupling between these two regions at
retrieval. Moreover, functional coupling during retrieval
was predictive of behavioral accuracy.<h4>Conclusions</h4>These
results shed new light on individual differences in
responsivity and connectivity between HF and VLPFC related
to genetic modulation of dopamine, a mechanism accounting at
least in part for individual differences in recognition
memory performance.},
Doi = {10.1016/j.biopsych.2006.03.078},
Key = {fds251995}
}
@article{fds252080,
Author = {Drabant, EM and Hariri, AR and Meyer-Lindenberg, A and Munoz, KE and Mattay, VS and Kolachana, BS and Egan, MF and Weinberger,
DR},
Title = {Catechol O-methyltransferase val158met genotype and neural
mechanisms related to affective arousal and
regulation.},
Journal = {Archives of general psychiatry},
Volume = {63},
Number = {12},
Pages = {1396-1406},
Year = {2006},
Month = {December},
ISSN = {0003-990X},
Abstract = {<h4>Context</h4>Catechol O-methyltransferase (COMT), the
major enzyme determining cortical dopamine flux, has a
common functional polymorphism (val(158)met) that affects
prefrontal function and working memory capacity and has also
been associated with anxiety and emotional
dysregulation.<h4>Objectives</h4>To examine COMT val(158)met
effects on corticolimbic circuitry reactivity and functional
connectivity during processing of biologically salient
stimuli, as well as the relationship to the temperamental
trait of novelty seeking.<h4>Design</h4>Within-subject
functional magnetic resonance imaging study.<h4>Setting</h4>National
Institute of Mental Health, Genes, Cognition, and Psychosis
Program, Bethesda, Md. Patients One hundred one healthy
subjects of both sexes.<h4>Results</h4>We found that the met
allele was associated with a dose-dependent increase in
hippocampal formation and ventrolateral prefrontal cortex
activation during viewing of faces displaying negative
emotion. In met/met homozygotes, limbic and prefrontal
regions showed increased functional coupling. Moreover, in
these same subjects, the magnitude of amygdala-orbitofrontal
coupling was inversely correlated with novelty seeking, an
index of temperamental inflexibility.<h4>Conclusions</h4>Our
results indicate that heritable variation in dopamine
neurotransmission associated with the met allele of the COMT
polymorphism results in heightened reactivity and
connectivity in corticolimbic circuits. This may reflect a
genetic predisposition for inflexible processing of
affective stimuli, a mechanism possibly accounting for
aspects of arousal and behavioral control that contribute to
emotional dysregulation previously reported in met/met
individuals.},
Doi = {10.1001/archpsyc.63.12.1396},
Key = {fds252080}
}
@article{Hariri2006d,
Author = {Hariri, AR and Brown, SM and Williamson, DE and Flory, JD and de Wit, H and Manuck, SB},
Title = {Preference for immediate over delayed rewards is associated
with magnitude of ventral striatal activity.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {26},
Number = {51},
Pages = {13213-13217},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15213, USA. haririar@upmc.edu},
Year = {2006},
Month = {December},
ISSN = {0270-6474},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17182771},
Keywords = {Adult • Basal Ganglia/*physiology • Behavior,
Addictive/physiopathology/psychology • Choice
Behavior/*physiology • Feedback, Psychological/physiology
• Female • Humans • Impulsive
Behavior/physiopathology/psychology • Male •
Middle Aged • Nerve Net/physiology • *Reward
• Risk Factors • Time Factors},
Abstract = {Discounting future outcomes as a function of their deferred
availability underlies much of human decision making.
Discounting, or preference for immediate over delayed
rewards of larger value, is often associated with
impulsivity and is a risk factor for addictive disorders
such as pathological gambling, cigarette smoking, and drug
and alcohol abuse. The ventral striatum (VS) is involved in
mediating behavioral responses and physiological states
associated with reward, and dysregulation of the VS
contributes to addiction, perhaps by affecting impulsive
decision-making. Behavioral tests of delay discounting (DD),
which index preference for smaller immediate over larger
delayed rewards, covary with impulsive tendencies in humans.
In the current study, we examined the relationship between
individual differences in DD, measured in a behavioral
assessment, and VS activity measured with blood oxygenation
level-dependent functional magnetic resonance imaging, in 45
adult volunteers. VS activity was determined using a task
involving positive and negative feedback with monetary
reward. Analyses revealed that individual differences in DD
correlate positively with magnitude of VS activation in
response to both positive and negative feedback, compared
with a no-feedback control condition. Variability in DD was
also associated with differential VS activation in response
to positive, compared with negative, feedback. Collectively,
our results suggest that increased preference for smaller
immediate over larger delayed rewards reflects both a
relatively indiscriminate and hyper-reactive VS circuitry.
They also highlight a specific neurocognitive mechanism that
may contribute to increased risk for addiction.},
Language = {eng},
Doi = {10.1523/jneurosci.3446-06.2006},
Key = {Hariri2006d}
}
@article{Neumann2006,
Author = {Neumann, SA and Brown, SM and Ferrell, RE and Flory, JD and Manuck, SB and Hariri, AR},
Title = {Human choline transporter gene variation is associated with
corticolimbic reactivity and autonomic-cholinergic
function.},
Journal = {Biological psychiatry},
Volume = {60},
Number = {10},
Pages = {1155-1162},
Address = {Department of Psychiatry and Behavioral Sciences, Eastern
Virginia Medical School, 825 Fairfax Avenue, Norfolk, VA
23501. Neumans@evms.edu},
Year = {2006},
Month = {November},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16876130},
Keywords = {Adult • Autonomic Nervous System/*physiology •
Brain Mapping • Cerebral Cortex/blood
supply/*physiology • Choice Behavior/physiology •
Electrocardiography • European Continental Ancestry
Group • Female • *Genetic Variation • Heart
Rate/physiology • Humans • Image Processing,
Computer-Assisted/methods • Limbic System/blood
supply/*physiology • Magnetic Resonance Imaging/methods
• Male • Membrane Transport Proteins/*genetics
• Middle Aged • Neural Pathways/blood
supply/*physiology • Neuropsychological Tests •
Oxygen/blood • Polymorphism, Single
Nucleotide},
Abstract = {<h4>Background</h4>Our previous work has shown genetic
variation in the human choline transporter gene (CHT1) to be
associated with depressive symptoms and autonomic cardiac
(cholinergic) dysregulation. Here, functional magnetic
resonance imaging (fMRI) was used to examine the relation
between a single nucleotide polymorphism (SNP) in CHT1 on
regional brain reactivity relevant to autonomic
(cholinergic) function.<h4>Methods</h4>Thirty-two
participants of European ancestry (18 men, 14 women; age:
33-54 years) completed an fMRI protocol using corticolimbic
reactivity and prefrontal inhibitory control paradigms.
Resting cholinergic function, as measured by heart rate
variability (HRV), was quantified from electrocardiogram.
Subjects were genotyped for a CHT1 G/T SNP.<h4>Results</h4>GG
homozygotes had greater right (R) dorsal amygdala (p <
.008), bilateral anterior cingulate (p < .009), and R
caudate reactivity (p < .015) than T-allele carriers. Heart
rate variability was related to R frontal cortex (Brodmann
Areas 6, 9, and 46), R hippocampal formation, bilateral
caudate, and bilateral anterior cingulate reactivity (p's <
.007).<h4>Conclusions</h4>CHT1 variation is related to
differences in a distributed corticolimbic circuitry
mediating behavioral and physiologic arousal. These
relations may contribute to a biological mechanism by which
genetic variation in cholinergic neurotransmission affects
cognition, mood, and autonomic cardiac function.},
Language = {eng},
Doi = {10.1016/j.biopsych.2006.03.059},
Key = {Neumann2006}
}
@article{fds252081,
Author = {Fisher, PM and Meltzer, CC and Ziolko, SK and Price, JC and Moses-Kolko,
EL and Berga, SL and Hariri, AR},
Title = {Capacity for 5-HT1A-mediated autoregulation predicts
amygdala reactivity.},
Journal = {Nature neuroscience},
Volume = {9},
Number = {11},
Pages = {1362-1363},
Year = {2006},
Month = {November},
ISSN = {1097-6256},
Abstract = {We examined the contribution of 5-HT1A autoreceptors (with
[11C]WAY100635 positron emission tomography) to amygdala
reactivity (with blood oxygenation level-dependent
functional magnetic resonance imaging) in 20 healthy adult
volunteers. We found a significant inverse relationship
wherein 5-HT1A autoreceptor density predicted a notable
30-44% of the variability in amygdala reactivity. Our data
suggest a potential molecular mechanism by which a reduced
capacity for negative feedback regulation of 5-HT release is
associated with increased amygdala reactivity.},
Doi = {10.1038/nn1780},
Key = {fds252081}
}
@article{Hariri2006a,
Author = {Hariri, AR and Lewis, DA},
Title = {Genetics and the future of clinical psychiatry.},
Journal = {The American journal of psychiatry},
Volume = {163},
Number = {10},
Pages = {1676-1678},
Year = {2006},
Month = {October},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17012672},
Keywords = {Forecasting • Genetics, Medical • Mental
Disorders/genetics • Psychiatry/*trends},
Language = {eng},
Doi = {10.1176/ajp.2006.163.10.1676},
Key = {Hariri2006a}
}
@article{fds251994,
Author = {Goldberg, TE and Straub, RE and Callicott, JH and Hariri, A and Mattay,
VS and Bigelow, L and Coppola, R and Egan, MF and Weinberger,
DR},
Title = {The G72/G30 gene complex and cognitive abnormalities in
schizophrenia.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {31},
Number = {9},
Pages = {2022-2032},
Year = {2006},
Month = {September},
ISSN = {0893-133X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16554747},
Abstract = {A recently discovered gene complex, G72/G30 (hereafter G72,
but now termed DAOA), was found to be associated with
schizophrenia and with bipolar disorder, possibly because of
an indirect effect on NMDA neurotransmission. In principle,
if G72 increases risk for psychosis by this mechanism, it
might impact with greater penetrance those cortically based
cognitive and neurophysiological functions associated with
NMDA signaling. We performed two independent family-based
association studies (one sample contained more than 200
families and the other more than 65) of multiple SNPs in the
G72 region and of multiple SNPs in the gene for D-amino acid
oxidase (DAAO), which may be modulated by G72. We examined
the relationship between select cognitive measures in
attention, working memory, and episodic memory and a
restricted set of G72 SNPs in over 600 normal controls,
schizophrenic patients, and their nonpsychotic siblings
using mixed model ANOVAs. We also determined genotype
effects on neurophysiology measures in normal controls using
the fMRI BOLD response obtained during activation procedures
involving either episodic memory or working memory. There
were no significant single G72 SNP associations and clinical
diagnosis in either sample, though one approached
significance (p=0.06). Diagnosis by genotype interaction
effects for G72 SNP 10 were significant for cognitive
variables assessing working memory and attention (p=0.05),
and at the trend level for episodic memory, such that in the
schizophrenia group an exaggerated allele load effect in the
predicted directions was observed. In the fMRI paradigms, a
strong effect of G72 SNP 10 genotype was observed on BOLD
activation in the hippocampus during the episodic memory
paradigm. Tests of association with DAAO were consistently
nonsignificant. We present evidence that SNP variations in
the G72 gene region increase risk of cognitive impairment in
schizophrenia. SNP variations were not strongly associated
with clinical diagnosis in family-based analyses.},
Doi = {10.1038/sj.npp.1301049},
Key = {fds251994}
}
@article{Hariri2006c,
Author = {Hariri, AR and Drabant, EM and Weinberger, DR},
Title = {Imaging genetics: perspectives from studies of genetically
driven variation in serotonin function and corticolimbic
affective processing.},
Journal = {Biological psychiatry},
Volume = {59},
Number = {10},
Pages = {888-897},
Address = {Department of Psychiatry, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania 15213-2593,
USA.},
Year = {2006},
Month = {May},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16442081},
Keywords = {Alleles • Amygdala/*physiopathology • *Diagnostic
Imaging • Emotions/*physiology • Genetic
Variation/*genetics • Humans • Mood
Disorders/*genetics/physiopathology • Neural
Pathways/physiopathology • Polymorphism,
Genetic/*genetics • Prefrontal Cortex/*physiopathology
• Serotonin/*genetics/physiology • Serotonin
Plasma Membrane Transport Proteins/genetics • Synaptic
Transmission/*genetics},
Abstract = {Advances in molecular biology and neuroimaging have provided
a unique opportunity to explore the relationships between
genes, brain, and behavior. In this review, we will briefly
outline the rationale for studying genetic effects on brain
function with neuroimaging. We will then use studies of
genetically driven variation in serotonin transporter
function on corticolimbic structure and function to
highlight the effectiveness of this strategy to delineate
biological pathways and mechanisms by which individual
differences in brain function emerge and potentially bias
behavior and risk for psychiatric illness. In a series of
studies, a relatively frequent regulatory variant of the
human serotonin transporter gene (5-HTTLPR) has been
demonstrated to bias the reactivity of the amygdala to
salient environmental cues. Moreover, the 5-HTTLPR affects
the development of a broader corticolimbic circuit and
alters the functional integration of emotional information
between the amygdala and medial prefrontal cortex. In turn,
corticolimbic circuit function predicts individual
differences in an experimental index of temperamental
anxiety and, thus, might reflect a predictive biological
marker of increased risk for mood disorders associated with
the 5-HTTLPR.},
Language = {eng},
Doi = {10.1016/j.biopsych.2005.11.005},
Key = {Hariri2006c}
}
@article{Brown2006a,
Author = {Brown, SM and Manuck, SB and Flory, JD and Hariri,
AR},
Title = {Neural basis of individual differences in impulsivity:
contributions of corticolimbic circuits for behavioral
arousal and control.},
Journal = {Emotion (Washington, D.C.)},
Volume = {6},
Number = {2},
Pages = {239-245},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA, USA.},
Year = {2006},
Month = {May},
ISSN = {1528-3542},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16768556},
Keywords = {Adult • Amygdala/*physiopathology •
Arousal/*physiology • Brain/*physiopathology •
Cerebral Cortex/*physiopathology • Female • Humans
• Impulse Control Disorders/diagnosis/*physiopathology
• Limbic System/*physiopathology • Magnetic
Resonance Imaging • Male • Middle Aged •
Nerve Net/*physiology • Neural Inhibition/*physiology
• Prefrontal Cortex/physiopathology • Severity of
Illness Index • *Social Control, Informal},
Abstract = {The objective of the current study was to analyze the neural
correlates of behavioral arousal and inhibitory control as
they relate to individual differences in impulsivity via
well-established functional MRI amygdala reactivity and
prefrontal inhibitory control paradigms in healthy adult
subjects. Impulsivity correlated positively with activity of
the bilateral ventral amygdala, parahippocampal gyrus,
dorsal anterior cingulate gyrus (BA 32), and bilateral
caudate. Conversely, impulsivity correlated negatively with
activity of the dorsal amygdala and ventral prefrontal
cortex (BA 47). Together, these findings suggest that
dispositional impulsivity is influenced by the functional
interplay of corticolimbic behavioral arousal and control
circuits.},
Language = {eng},
Doi = {10.1037/1528-3542.6.2.239},
Key = {Brown2006a}
}
@article{fds251993,
Author = {Meyer-Lindenberg, A and Buckholtz, JW and Kolachana, B and R Hariri,
A and Pezawas, L and Blasi, G and Wabnitz, A and Honea, R and Verchinski,
B and Callicott, JH and Egan, M and Mattay, V and Weinberger,
DR},
Title = {Neural mechanisms of genetic risk for impulsivity and
violence in humans.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {103},
Number = {16},
Pages = {6269-6274},
Year = {2006},
Month = {April},
ISSN = {0027-8424},
Abstract = {Neurobiological factors contributing to violence in humans
remain poorly understood. One approach to this question is
examining allelic variation in the X-linked monoamine
oxidase A (MAOA) gene, previously associated with impulsive
aggression in animals and humans. Here, we have studied the
impact of a common functional polymorphism in MAOA on brain
structure and function assessed with MRI in a large sample
of healthy human volunteers. We show that the low expression
variant, associated with increased risk of violent behavior,
predicted pronounced limbic volume reductions and
hyperresponsive amygdala during emotional arousal, with
diminished reactivity of regulatory prefrontal regions,
compared with the high expression allele. In men, the low
expression allele is also associated with changes in
orbitofrontal volume, amygdala and hippocampus
hyperreactivity during aversive recall, and impaired
cingulate activation during cognitive inhibition. Our data
identify differences in limbic circuitry for emotion
regulation and cognitive control that may be involved in the
association of MAOA with impulsive aggression, suggest
neural systems-level effects of X-inactivation in human
brain, and point toward potential targets for a biological
approach toward violence.},
Doi = {10.1073/pnas.0511311103},
Key = {fds251993}
}
@article{Hariri2006b,
Author = {Hariri, AR and Holmes, A},
Title = {Genetics of emotional regulation: the role of the serotonin
transporter in neural function.},
Journal = {Trends in cognitive sciences},
Volume = {10},
Number = {4},
Pages = {182-191},
Address = {Department of Psychiatry and Center for the Neural Basis of
Cognition, University of Pittsburgh, Pittsburgh,
Pennsylvania 15213, USA. haririar@upmc.edu},
Year = {2006},
Month = {April},
ISSN = {1364-6613},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16530463},
Keywords = {Amygdala/pathology/physiology • Animals •
Emotions/*physiology • *Genetic Variation • Humans
• Models, Neurological • Mood Disorders/classification/*genetics
• Serotonin Plasma Membrane Transport
Proteins/*genetics/metabolism},
Abstract = {Identifying biological mechanisms through which genes lead
to individual differences in emotional behavior is paramount
to our understanding of how such differences confer risk for
neuropsychiatric illness. The emergence of techniques such
as in vivo imaging of brain function in humans and genetic
engineering in rodents has provided important new insights
into the impact of serotonin (5-HT), a key modulator of
emotional behavior, on neural systems subserving anxiety and
depression. A major finding has been the discovery of
genetic variation in a crucial regulatory molecule within
the 5-HT system, the 5HT transporter (5-HTT), and its
influence on emotional traits. The study of the 5-HTT
provides a new foundation for understanding the
neurobiological and genetic basis of emotional regulation
and affective illness.},
Language = {eng},
Doi = {10.1016/j.tics.2006.02.011},
Key = {Hariri2006b}
}
@article{Brown2006b,
Author = {Brown, SM and Hariri, AR},
Title = {Neuroimaging studies of serotonin gene polymorphisms:
exploring the interplay of genes, brain, and
behavior.},
Journal = {Cognitive, affective & behavioral neuroscience},
Volume = {6},
Number = {1},
Pages = {44-52},
Address = {Department of Psychiatry, University of Pittsburgh School of
Medicine, Western Psychiatric Institute and Clinic, 3811
O'Hara Street, Room E-729, Pittsburgh, PA 15213-2593,
USA.},
Year = {2006},
Month = {March},
ISSN = {1530-7026},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16869228},
Keywords = {Animals • Behavior/*physiology • Brain/*anatomy \&
histology/*physiology • Brain Mapping • Diagnostic
Imaging/methods • Emotions/physiology • Humans
• Nerve Net • *Polymorphism, Genetic •
Serotonin/*genetics},
Abstract = {Because of the unique ability it provides to investigate
information processing at the level of neural systems,
functional neuroimaging is a powerful tool to explore the
relationship between genes, brain, and behavior. Recently,
functional neuroimaging has provided dramatic illustrations
of how a promoter polymorphism in the human serotonin
transporter gene, which has been weakly related to several
dimensions of emotional behaviors (such as neuroticism and
anxiety traits), is strongly related to the engagement of
neural systems--namely, the amygdala and subgenual
prefrontal cortex, subserving emotional information
processing. This review will outline the experimental
strategy by which these genetic effects on brain function
have been explored and highlight the effectiveness of this
strategy to delineate biological pathways and mechanisms
contributing to the emergence of individual differences in
brain function that potentially bias behavior and risk for
psychiatric illness.},
Language = {eng},
Doi = {10.3758/cabn.6.1.44},
Key = {Brown2006b}
}
@article{Viding2006,
Author = {Viding, E and Williamson, DE and Hariri, AR},
Title = {Developmental imaging genetics: challenges and promises for
translational research.},
Journal = {Development and psychopathology},
Volume = {18},
Number = {3},
Pages = {877-892},
Address = {University College London.},
Year = {2006},
Month = {January},
ISSN = {0954-5794},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17152405},
Keywords = {Antisocial Personality Disorder/genetics/pathology/physiopathology
• Brain/*pathology/*physiopathology •
*Electroencephalography • Humans •
*Interdisciplinary Communication • *Magnetic Resonance
Imaging • *Mental Disorders/genetics/pathology/physiopathology
• Research/*standards • Serotonin/genetics},
Abstract = {Advances in molecular biology, neuroimaging, genetic
epidemiology, and developmental psychopathology have
provided a unique opportunity to explore the interplay of
genes, brain, and behavior within a translational research
framework. Herein, we begin by outlining an experimental
strategy by which genetic effects on brain function can be
explored using neuroimaging, namely, imaging genetics. We
next describe some major findings in imaging genetics to
highlight the effectiveness of this strategy for delineating
biological pathways and mechanisms by which individual
differences in brain function emerge and potentially bias
behavior and risk for psychiatric illness. We then discuss
the importance of applying imaging genetics to the study of
psychopathology within a developmental framework. By
beginning to move toward a systems-level approach to
understanding pathways to behavioral outcomes as they are
expressed across development, it is anticipated that we will
move closer to understanding the complexities of the
specific mechanisms involved in the etiology of psychiatric
disease. Despite the numerous challenges that lie ahead, we
believe that developmental imaging genetics has potential to
yield highly informative results that will ultimately
translate into public health benefits. We attempt to set out
guidelines and provide exemplars that may help in designing
fruitful translational research applications that
incorporate a developmental imaging genetics
strategy.},
Language = {eng},
Doi = {10.1017/s0954579406060433},
Key = {Viding2006}
}
@article{Hariri2006e,
Author = {Hariri, AR and Brown, SM},
Title = {Serotonin.},
Journal = {The American journal of psychiatry},
Volume = {163},
Number = {1},
Pages = {12},
Year = {2006},
Month = {January},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16390882},
Keywords = {Amygdala/*metabolism/physiopathology • European
Continental Ancestry Group/genetics • Gene Frequency
• Genetic Variation • Genotype • Humans
• Mood Disorders/*genetics/physiopathology •
Serotonin/genetics/metabolism/*physiology • Serotonin
Plasma Membrane Transport Proteins/*genetics/physiology},
Language = {eng},
Doi = {10.1176/appi.ajp.163.1.12},
Key = {Hariri2006e}
}
@article{Mattay2006,
Author = {Mattay, VS and Fera, F and Tessitore, A and Hariri, AR and Berman, KF and Das, S and Meyer-Lindenberg, A and Goldberg, TE and Callicott, JH and Weinberger, DR},
Title = {Neurophysiological correlates of age-related changes in
working memory capacity.},
Journal = {Neuroscience letters},
Volume = {392},
Number = {1-2},
Pages = {32-37},
Address = {Clinical Brain Disorders Branch, Genes, Cognition and
Psychosis Program, National Institute of Mental Health,
National Institutes of Health, 9000 Rockville Pike,
Bethesda, MD 20892, USA. vsm@mail.nih.gov},
Year = {2006},
Month = {January},
ISSN = {0304-3940},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16213083},
Keywords = {Adult • Age Factors • Aged •
Aging/*physiology • Drug Combinations • Female
• Humans • Magnetic Resonance Imaging/methods
• Male • Memory, Short-Term/*physiology •
Middle Aged • Neuropsychological Tests/statistics \&
numerical data • Peroxides/blood • Prefrontal
Cortex/blood supply/*physiology • Reaction
Time/physiology • Urea/analogs \& derivatives/blood},
Abstract = {Cognitive abilities such as working memory (WM) capacity
decrease with age. To determine the neurophysiological
correlates of age-related reduction in working memory
capacity, we studied 10 young subjects (<35 years of age;
mean age=29) and twelve older subjects (>55 years of age;
mean age=59) with whole brain blood oxygenation-level
dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a
SPIRAL FLASH pulse sequence (TE=24 ms, TR=56 ms, FA=60
degrees , voxel dimensions=3.75 mm(3)). Subjects performed a
modified version of the "n" back working memory task at
different levels of increasing working memory load (1-Back,
2-Back and 3-Back). Older subjects performed as well as the
younger subjects at 1-Back (p=0.4), but performed worse than
the younger subjects at 2-Back (p<0.01) and 3-Back (p=0.06).
Older subjects had significantly longer reaction time (RT)
than younger subjects (p<0.04) at all levels of task
difficulty. Image analysis using SPM 99 revealed a similar
distribution of cortical activity between younger and older
subjects at all task levels. However, an analysis of
variance revealed a significant group x task interaction in
the prefrontal cortex bilaterally; within working memory
capacity, as in 1-Back when the older subjects performed as
well as the younger subjects, they showed greater prefrontal
cortical (BA 9) activity bilaterally. At higher working
memory loads, however, when they performed worse then the
younger subjects, the older subjects showed relatively
reduced activity in these prefrontal regions. These data
suggest that, within capacity, compensatory mechanisms such
as additional prefrontal cortical activity are called upon
to maintain proficiency in task performance. As cognitive
demand increases, however, they are pushed past a threshold
beyond which physiological compensation cannot be made and,
a decline in performance occurs.},
Language = {eng},
Doi = {10.1016/j.neulet.2005.09.025},
Key = {Mattay2006}
}
@article{Drabant2006,
Author = {Drabant, E. M. and Hariri, A. R. and Meyer-Lindenberg, A. and Munoz, K. E. and Mattay, V. S. and Kolachana, B. S. and Egan, M. F. and Weinberger, D. R.},
Title = {Catechol O-methyltransferase val158met genotype and neural
mechanisms related to affective arousal and
regulation},
Journal = {Archives of general psychiatry},
Volume = {63},
Number = {12},
Pages = {1396--406},
Address = {Genes, Cognition, and Psychosis Program, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health/DHHS, 10 Center Drive, Bethesda, MD
20892, USA.},
Year = {2006},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17146014},
Keywords = {Adult • Affect/*physiology/*radiation effects •
Affective Symptoms/diagnosis/*genetics •
Amygdala/physiology • Arousal/genetics/*physiology
• Brain Mapping/methods • Catechol
O-Methyltransferase/*genetics • Exploratory
Behavior/physiology • Facial Expression • Female
• Genotype • Humans • Limbic
System/*physiology • Magnetic Resonance
Imaging/statistics \& numerical data • Male •
Methionine/genetics • Neural Pathways/physiology •
Oxygen/blood • Polymorphism, Genetic/*physiology •
Prefrontal Cortex/*physiology • Synaptic
Transmission/physiology • Temperament/physiology •
Valine/genetics • Visual Perception/physiology},
Abstract = {CONTEXT: Catechol O-methyltransferase (COMT), the major
enzyme determining cortical dopamine flux, has a common
functional polymorphism (val(158)met) that affects
prefrontal function and working memory capacity and has also
been associated with anxiety and emotional dysregulation.
OBJECTIVES: To examine COMT val(158)met effects on
corticolimbic circuitry reactivity and functional
connectivity during processing of biologically salient
stimuli, as well as the relationship to the temperamental
trait of novelty seeking. DESIGN: Within-subject functional
magnetic resonance imaging study. SETTING: National
Institute of Mental Health, Genes, Cognition, and Psychosis
Program, Bethesda, Md. Patients One hundred one healthy
subjects of both sexes. RESULTS: We found that the met
allele was associated with a dose-dependent increase in
hippocampal formation and ventrolateral prefrontal cortex
activation during viewing of faces displaying negative
emotion. In met/met homozygotes, limbic and prefrontal
regions showed increased functional coupling. Moreover, in
these same subjects, the magnitude of amygdala-orbitofrontal
coupling was inversely correlated with novelty seeking, an
index of temperamental inflexibility. CONCLUSIONS: Our
results indicate that heritable variation in dopamine
neurotransmission associated with the met allele of the COMT
polymorphism results in heightened reactivity and
connectivity in corticolimbic circuits. This may reflect a
genetic predisposition for inflexible processing of
affective stimuli, a mechanism possibly accounting for
aspects of arousal and behavioral control that contribute to
emotional dysregulation previously reported in met/met
individuals.},
Language = {eng},
Doi = {10.1001/archpsyc.63.12.1396},
Key = {Drabant2006}
}
@article{Fisher2006,
Author = {Fisher, P. M. and Meltzer, C. C. and Ziolko, S. K. and Price, J. C. and Moses-Kolko, E. L. and Berga, S. L. and Hariri, A. R.},
Title = {Capacity for 5-HT1A-mediated autoregulation predicts
amygdala reactivity},
Journal = {Nature neuroscience},
Volume = {9},
Number = {11},
Pages = {1362--3},
Address = {Department of Psychiatry, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania 15213,
USA.},
Year = {2006},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17013380},
Keywords = {Adult • Amygdala/*physiology •
Depression/metabolism • Feedback/physiology •
Homeostasis/*physiology • Humans • Magnetic
Resonance Imaging • Oxygen/blood •
Piperazines/pharmacology • Positron-Emission Tomography
• Pyridines/pharmacology • Receptor, Serotonin,
5-HT1A/drug effects/*physiology • Serotonin
Antagonists/pharmacology},
Abstract = {We examined the contribution of 5-HT1A autoreceptors (with
[11C]WAY100635 positron emission tomography) to amygdala
reactivity (with blood oxygenation level-dependent
functional magnetic resonance imaging) in 20 healthy adult
volunteers. We found a significant inverse relationship
wherein 5-HT1A autoreceptor density predicted a notable
30-44\% of the variability in amygdala reactivity. Our data
suggest a potential molecular mechanism by which a reduced
capacity for negative feedback regulation of 5-HT release is
associated with increased amygdala reactivity.},
Language = {eng},
Doi = {10.1038/nn1780},
Key = {Fisher2006}
}
@article{fds251992,
Author = {Fera, F and Weickert, TW and Goldberg, TE and Tessitore, A and Hariri,
A and Das, S and Lee, S and Zoltick, B and Meeter, M and Myers, CE and Gluck,
MA and Weinberger, DR and Mattay, VS},
Title = {Neural mechanisms underlying probabilistic category learning
in normal aging.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {25},
Number = {49},
Pages = {11340-11348},
Year = {2005},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16339029},
Abstract = {Probabilistic category learning engages neural circuitry
that includes the prefrontal cortex and caudate nucleus, two
regions that show prominent changes with normal aging.
However, the specific contributions of these brain regions
are uncertain, and the effects of normal aging have not been
examined previously in probabilistic category learning. In
the present study, using a blood oxygenation level-dependent
functional magnetic resonance imaging block design, 18
healthy young adults (mean age, 25.5 +/- 2.6 years) and 15
older adults (mean age, 67.1 +/- 5.3 years) were assessed on
the probabilistic category learning "weather prediction"
test. Whole-brain functional images acquired using a 1.5T
scanner (General Electric, Milwaukee, WI) with gradient
echo, echo planar imaging (3/1 mm; repetition time, 3000 ms;
echo time, 50 ms) were analyzed using second-level
random-effects procedures [SPM99 (Statistical Parametric
Mapping)]. Young and older adults displayed equivalent
probabilistic category learning curves, used similar
strategies, and activated analogous neural networks,
including the prefrontal and parietal cortices and the
caudate nucleus. However, the extent of caudate and
prefrontal activation was less and parietal activation was
greater in older participants. The percentage correct and
reaction time were mainly positively correlated with caudate
and prefrontal activation in young individuals but
positively correlated with prefrontal and parietal cortices
in older individuals. Differential activation within a
circumscribed neural network in the context of equivalent
learning suggests that some brain regions, such as the
parietal cortices, may provide a compensatory mechanism for
healthy older adults in the context of deficient prefrontal
cortex and caudate nuclei responses.},
Doi = {10.1523/jneurosci.2736-05.2005},
Key = {fds251992}
}
@article{fds252011,
Author = {Dahl, RE and Hariri, AR},
Title = {Lessons from G. Stanley Hall: Connecting new research in
biological sciences to the study of adolescent
development},
Journal = {Journal of Research on Adolescence},
Volume = {15},
Number = {4},
Pages = {367-382},
Publisher = {WILEY},
Year = {2005},
Month = {December},
ISSN = {1050-8392},
Doi = {10.1111/j.1532-7795.2005.00102.x},
Key = {fds252011}
}
@article{Lerner2005,
Author = {Lerner, JS and Gonzalez, RM and Dahl, RE and Hariri, AR and Taylor,
SE},
Title = {Facial expressions of emotion reveal neuroendocrine and
cardiovascular stress responses.},
Journal = {Biological psychiatry},
Volume = {58},
Number = {9},
Pages = {743-750},
Address = {Department of Social and Decision Sciences, Carnegie Mellon
University, Pittsburgh, Pennsylvania 15213, USA.
jlerner@cmu.edu},
Year = {2005},
Month = {November},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16256075},
Keywords = {Adult • *Cardiovascular Physiological Phenomena •
Emotions/*physiology • *Facial Expression •
Fear/physiology/psychology • Female •
Hemodynamics/physiology • Humans •
Hydrocortisone/blood • Male • Neurosecretory
Systems/*physiology • Saliva/metabolism • Stress,
Psychological/*physiopathology},
Abstract = {<h4>Background</h4>The classic conception of stress involves
undifferentiated negative affect and corresponding
biological reactivity. The present study hypothesized a new
conception that disaggregates stress into emotion-specific,
contrasting patterns of biological response.<h4>Methods</h4>Ninety-two
healthy adults engaged in stress-challenge tasks, during
which cardiovascular responses, hypothalamic-pituitary-adrenocortical
(HPA) axis responses (i.e., cortisol), emotional expressions
(i.e., facial muscle movements), and subjective emotional
experience (self-reported) were assessed.<h4>Results</h4>Pronounced
individual differences emerged in specific emotional
responses to the stressors. Analyses of facial expressions
revealed that the more fear individuals displayed in
response to the stressors, the higher their cardiovascular
and cortisol responses to stress. By contrast, the more
anger and disgust (indignation) individuals displayed in
response to the same stressors, the lower their cortisol
levels and cardiovascular responses. Individual differences
in optimistic appraisals appeared to mediate these
correlated patterns.<h4>Conclusions</h4>Facial expressions
of emotion signal biological responses to stress. Fear
expressions signal elevated cortisol and cardiovascular
reactivity; anger and disgust signal attenuated cortisol and
cardiovascular reactivity, patterns that implicate
individual differences in stress appraisals. Rather than
conceptualizing stress as generalized negative affect,
studies can be informed by this emotion-specific approach to
stress responses.},
Language = {eng},
Doi = {10.1016/j.biopsych.2005.08.011},
Key = {Lerner2005}
}
@article{Brown2005,
Author = {Brown, SM and Peet, E and Manuck, SB and Williamson, DE and Dahl, RE and Ferrell, RE and Hariri, AR},
Title = {A regulatory variant of the human tryptophan hydroxylase-2
gene biases amygdala reactivity},
Journal = {Molecular Psychiatry},
Volume = {10},
Number = {9},
Pages = {805},
Publisher = {Springer Nature},
Address = {Department of Psychiatry, University of Pittsburgh,
Pittsburgh, PA 15213, USA.},
Year = {2005},
Month = {September},
ISSN = {1359-4184},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16044172},
Keywords = {Amygdala/*enzymology/physiology • Brain/anatomy \&
histology/physiology • Emotions/*physiology • Gene
Frequency • *Genetic Variation • Genotype •
Humans • Magnetic Resonance Imaging • Oxygen/blood
• Sequence Deletion • Tryptophan
Hydroxylase/*genetics},
Abstract = {Recent studies have indicated that a newly identified second
isoform of the tryptophan hydroxylase gene (TPH2) is
preferentially involved in the rate-limiting synthesis of
neuronal serotonin. Genetic variation in the human TPH2 gene
(hTPH2) has been associated with altered in vitro enzyme
activity as well as increased risk for mood disorders. Here,
we provide the first in vivo evidence that a relatively
frequent regulatory variant (G(-844)T) of hTPH2 biases the
reactivity of the amygdala, a neural structure critical in
the generation and regulation of emotional
behaviors.},
Language = {eng},
Doi = {10.1038/sj.mp.4001725},
Key = {Brown2005}
}
@article{Lee2005,
Author = {Lee, M and Bailer, UF and Frank, GK and Henry, SE and Meltzer, CC and Price, JC and Mathis, CA and Putnam, KT and Ferrell, RE and Hariri, AR and Kaye, WH},
Title = {Relationship of a 5-HT transporter functional polymorphism
to 5-HT1A receptor binding in healthy women.},
Journal = {Molecular psychiatry},
Volume = {10},
Number = {8},
Pages = {715-716},
Year = {2005},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15940302},
Keywords = {Amygdala/physiology • Female • Genotype •
Humans • Membrane Glycoproteins/*genetics •
Membrane Transport Proteins/*genetics • Nerve Tissue
Proteins/*genetics • Neurons/physiology •
*Polymorphism, Genetic • Receptor, Serotonin,
5-HT1A/*genetics • Reference Values • Serotonin
Plasma Membrane Transport Proteins • Statistics,
Nonparametric},
Language = {eng},
Doi = {10.1038/sj.mp.4001680},
Key = {Lee2005}
}
@article{Meyer-Lindenberg2005,
Author = {Meyer-Lindenberg, A and Hariri, AR and Munoz, KE and Mervis, CB and Mattay, VS and Morris, CA and Berman, KF},
Title = {Neural correlates of genetically abnormal social cognition
in Williams syndrome.},
Journal = {Nature neuroscience},
Volume = {8},
Number = {8},
Pages = {991-993},
Address = {Section on Integrative Neuroimaging, National Institute of
Mental Health, National Institutes of Health, Department of
Health and Human Services, Bethesda, Maryland 20892, USA.
andreasml@nih.gov},
Year = {2005},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16007084},
Keywords = {Amygdala/physiopathology • Anxiety/physiopathology
• Brain/*physiopathology • Brain Mapping •
Case-Control Studies • *Cognition • Frontal
Lobe/physiopathology • Humans • *Magnetic
Resonance Imaging • Prefrontal Cortex/physiopathology
• *Social Behavior • Williams Syndrome/*physiopathology/*psychology},
Abstract = {Williams-Beuren syndrome (WBS), caused by a microdeletion of
approximately 21 genes on chromosome 7q11.23, is
characterized by unique hypersociability combined with
increased non-social anxiety. Using functional neuroimaging,
we found reduced amygdala activation in individuals with WBS
for threatening faces but increased activation for
threatening scenes, relative to matched normal controls.
Activation and interactions of prefrontal regions linked to
amygdala, especially orbitofrontal cortex, were abnormal,
suggesting a genetically controlled neural circuitry for
regulating human social behavior.},
Language = {eng},
Doi = {10.1038/nn1494},
Key = {Meyer-Lindenberg2005}
}
@article{fds251989,
Author = {Lieberman, MD and Hariri, A and Jarcho, JM and Eisenberger, NI and Bookheimer, SY},
Title = {An fMRI investigation of race-related amygdala activity in
African-American and Caucasian-American individuals.},
Journal = {Nature neuroscience},
Volume = {8},
Number = {6},
Pages = {720-722},
Year = {2005},
Month = {June},
ISSN = {1097-6256},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15880106},
Abstract = {Functional magnetic resonance imaging (fMRI) was used to
examine the nature of amygdala sensitivity to race. Both
African-American and Caucasian-American individuals showed
greater amygdala activity to African-American targets than
to Caucasian-American targets, suggesting that race-related
amygdala activity may result from cultural learning rather
than from the novelty of other races. Additionally, verbal
encoding of African-American targets produced significantly
less amygdala activity than perceptual encoding of
African-American targets.},
Doi = {10.1038/nn1465},
Key = {fds251989}
}
@article{fds251990,
Author = {Bertolino, A and Arciero, G and Rubino, V and Latorre, V and De Candia,
M and Mazzola, V and Blasi, G and Caforio, G and Hariri, A and Kolachana,
B and Nardini, M and Weinberger, DR and Scarabino,
T},
Title = {Variation of human amygdala response during threatening
stimuli as a function of 5'HTTLPR genotype and personality
style.},
Journal = {Biological psychiatry},
Volume = {57},
Number = {12},
Pages = {1517-1525},
Year = {2005},
Month = {June},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15953488},
Abstract = {<h4>Background</h4>In the brain, processing of fearful
stimuli engages the amygdala, and the variability of its
activity is associated with genetic factors as well as with
emotional salience. The objective of this study was to
explore the relevance of personality style for variability
of amygdala response.<h4>Methods</h4>We studied two groups
(n=14 in each group) of healthy subjects categorized by
contrasting cognitive styles with which they attribute
salience to fearful stimuli: so-called phobic prone subjects
who exaggerate potential environmental threat versus
so-called eating disorders prone subjects who tend to be
much less centered around fear. The two groups underwent
functional magnetic resonance imaging (fMRI) at 3T during
performance of a perceptual task of threatening stimuli and
they were also matched for the genotype of the 5' variable
number tandem repeat (VNTR) polymorphism in the serotonin
transporter.<h4>Results</h4>The fMRI results indicated that
phobic prone subjects selectively recruit the amygdala to a
larger extent than eating disorders prone subjects. Activity
in the amygdala was also independently predicted by
personality style and genotype of the serotonin transporter.
Moreover, brain activity during a working memory task did
not differentiate the two groups.<h4>Conclusions</h4>The
results of the present study suggest that aspects of
personality style are rooted in biological responses of the
fear circuitry associated with processing of environmental
information.},
Doi = {10.1016/j.biopsych.2005.02.031},
Key = {fds251990}
}
@article{Pezawas2005,
Author = {Pezawas, L and Meyer-Lindenberg, A and Drabant, EM and Verchinski,
BA and Munoz, KE and Kolachana, BS and Egan, MF and Mattay, VS and Hariri,
AR and Weinberger, DR},
Title = {5-HTTLPR polymorphism impacts human cingulate-amygdala
interactions: a genetic susceptibility mechanism for
depression.},
Journal = {Nature neuroscience},
Volume = {8},
Number = {6},
Pages = {828-834},
Address = {Genes, Cognition and Psychosis Program, National Institute
of Mental Health, National Institutes of Health, 10 Center
Drive 4S235, Bethesda, Maryland 20892-1379,
USA.},
Year = {2005},
Month = {June},
ISSN = {1097-6256},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15880108},
Keywords = {Amygdala/*metabolism/pathology/physiopathology •
Anthropometry • Anxiety Disorders/*genetics/metabolism/pathology
• Atrophy/genetics/metabolism/pathology • Brain
Chemistry/genetics • Brain Mapping • Depressive
Disorder/*genetics/metabolism/pathology •
Fear/physiology/psychology • Genetic Predisposition to
Disease/*genetics • Gyrus Cinguli/*metabolism/pathology/physiopathology
• Humans • Magnetic Resonance Imaging •
Membrane Glycoproteins/*genetics • Membrane Transport
Proteins/*genetics • Mutation/genetics • Nerve
Tissue Proteins/*genetics • Neural Pathways/metabolism/pathology/physiopathology
• Neuropsychological Tests • Polymorphism,
Genetic/genetics • Questionnaires •
Serotonin/metabolism • Serotonin Plasma Membrane
Transport Proteins},
Abstract = {Carriers of the short allele of a functional 5' promoter
polymorphism of the serotonin transporter gene have
increased anxiety-related temperamental traits, increased
amygdala reactivity and elevated risk of depression. Here,
we used multimodal neuroimaging in a large sample of healthy
human subjects to elucidate neural mechanisms underlying
this complex genetic association. Morphometrical analyses
showed reduced gray matter volume in short-allele carriers
in limbic regions critical for processing of negative
emotion, particularly perigenual cingulate and amygdala.
Functional analysis of those regions during perceptual
processing of fearful stimuli demonstrated tight coupling as
a feedback circuit implicated in the extinction of negative
affect. Short-allele carriers showed relative uncoupling of
this circuit. Furthermore, the magnitude of coupling
inversely predicted almost 30% of variation in temperamental
anxiety. These genotype-related alterations in anatomy and
function of an amygdala-cingulate feedback circuit critical
for emotion regulation implicate a developmental,
systems-level mechanism underlying normal emotional
reactivity and genetic susceptibility for
depression.},
Language = {eng},
Doi = {10.1038/nn1463},
Key = {Pezawas2005}
}
@article{Callicott2005,
Author = {Callicott, JH and Straub, RE and Pezawas, L and Egan, MF and Mattay, VS and Hariri, AR and Verchinski, BA and Meyer-Lindenberg, A and Balkissoon,
R and Kolachana, B and Goldberg, TE and Weinberger,
DR},
Title = {Variation in DISC1 affects hippocampal structure and
function and increases risk for schizophrenia.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {102},
Number = {24},
Pages = {8627-8632},
Address = {Genes, Cognition, and Psychosis Program, Clinical Brain
Disorders Branch, Division of Intramural Research, National
Institute of Mental Health, National Institutes of Health,
Bethesda, MD 20892, USA. callicottj@mail.nih.gov},
Year = {2005},
Month = {June},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15939883},
Keywords = {Adult • African Americans • *Alleles •
European Continental Ancestry Group • Female •
Haplotypes/genetics • Hippocampus/*anatomy \&
histology/metabolism/*physiology • Humans •
Magnetic Resonance Imaging • Male • Nerve Tissue
Proteins/*genetics/metabolism • Polymorphism, Single
Nucleotide/genetics • Psychomotor Performance/physiology
• Risk Factors • Schizophrenia/*genetics},
Abstract = {Disrupted-in-schizophrenia 1 (DISC1) is a promising
schizophrenia candidate gene expressed predominantly within
the hippocampus. We typed 12 single-nucleotide polymorphisms
(SNPs) that covered the DISC1 gene. A three-SNP haplotype
[hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of
the gene was associated with schizophrenia in a family-based
sample (P = 0.002). A common nonconservative SNP (Ser704Cys)
(rs821616) within this haplotype was associated with
schizophrenia (P = 0.004). Based on primary expression of
DISC1 in hippocampus, we hypothesized that allelic variation
at Ser704Cys would have a measurable impact on hippocampal
structure and function as assayed via specific
hippocampus-related intermediate phenotypes. In addition to
overtransmission in schizophrenia, the Ser allele was
associated with altered hippocampal structure and function
in healthy subjects, including reduced hippocampal gray
matter volume and altered engagement of the hippocampus
during several cognitive tasks assayed with functional
magnetic resonance imaging. These convergent data suggest
that allelic variation within DISC1, either at Ser704Cys or
haplotypes monitored by it, increases the risk for
schizophrenia and that the mechanism of this effect involves
structural and functional alterations in the hippocampal
formation.},
Language = {eng},
Doi = {10.1073/pnas.0500515102},
Key = {Callicott2005}
}
@article{Tessitore2005,
Author = {Tessitore, A and Hariri, AR and Fera, F and Smith, WG and Das, S and Weinberger, DR and Mattay, VS},
Title = {Functional changes in the activity of brain regions
underlying emotion processing in the elderly.},
Journal = {Psychiatry research},
Volume = {139},
Number = {1},
Pages = {9-18},
Address = {Clinical Brain Disorders Branch, Genes, Cognition and
Psychosis Program, National Institute of Mental Health,
National Institutes of Health, 10 Center Drive, Bldg. 10,
Room 3C108, Bethesda, MD 20892-1384, USA.},
Year = {2005},
Month = {May},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15936178},
Keywords = {Adult • *Affect • Aged • Aged, 80 and over
• Aging/physiology • Amygdala/anatomy \& histology
• Brain/*anatomy \& histology/*metabolism • Humans
• *Magnetic Resonance Imaging • Middle Aged •
Oxygen/metabolism • Prefrontal Cortex/anatomy \&
histology/metabolism},
Abstract = {Aging is associated with a decline in both cognitive and
motor abilities that reflects deterioration of underlying
brain circuitry. While age-related alterations have also
been described in brain regions underlying emotional
behavior (e.g., the amygdala), the functional consequence of
such changes is less clear. To this end, we used blood
oxygenation-level dependent (BOLD) functional magnetic
resonance imaging (fMRI) to explore age-related changes in
brain regions underlying emotion processing. Twelve young
(age <30 years) and 14 elderly subjects (age >60 years) were
studied with BOLD fMRI during a paradigm that involved
perceptual processing of fearful and threatening stimuli.
Consistent with previous reports, direct group comparisons
revealed relatively increased BOLD fMRI responses in
prefrontal cortical regions, including Broca's area, and
relatively decreased responses in the amygdala and posterior
fusiform gyri in elderly subjects. Importantly, additional
analyses using an elderly-specific brain template for
spatial normalization of the elderly BOLD fMRI data
confirmed these divergent regional response patterns. While
there was no difference between groups in accuracy on the
task, elderly subjects were significantly slower (delayed
reaction times) in performing the task. Our current data
suggest that elderly subjects engage a more distributed
neocortical network during the perceptual processing of
emotional facial expressions. In light of recent converging
data from two other studies, our observed effects may
reflect age-related compensatory responses and/or
alternative strategies in processing emotions, as the
elderly appear to engage cognitive/linguistic systems in the
context of reduced sensory and/or limbic
responses.},
Language = {eng},
Doi = {10.1016/j.pscychresns.2005.02.009},
Key = {Tessitore2005}
}
@article{Hariri2005,
Author = {Hariri, AR and Drabant, EM and Munoz, KE and Kolachana, BS and Mattay,
VS and Egan, MF and Weinberger, DR},
Title = {A susceptibility gene for affective disorders and the
response of the human amygdala.},
Journal = {Archives of general psychiatry},
Volume = {62},
Number = {2},
Pages = {146-152},
Address = {Genes, Cognition and Psychosis Program, National Institute
of Mental Health Intramural Research Program, National
Institutes of Health, US Department of Health and Human
Services, Bethesda, MD 20892, USA.},
Year = {2005},
Month = {February},
ISSN = {0003-990X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15699291},
Keywords = {Adult • Amygdala/*physiology • Anger/physiology
• Emotions/*physiology • Facial Expression •
Fear/physiology • Female • Genetic Predisposition
to Disease/genetics • Genetic Variation/physiology
• Genotype • Humans • Magnetic Resonance
Imaging • Male • Membrane Glycoproteins/*genetics
• Membrane Transport Proteins/*genetics • Mood
Disorders/diagnosis/epidemiology/*genetics • Nerve
Tissue Proteins/*genetics • Oxygen/blood •
Serotonin Plasma Membrane Transport Proteins • Sex
Distribution • Stress, Psychological/diagnosis/genetics
• Transcription, Genetic/physiology • Visual
Perception/physiology},
Abstract = {<h4>Background</h4>A common regulatory variant (5-HTTLPR) in
the human serotonin transporter gene (SLC6A4), resulting in
altered transcription and transporter availability, has been
associated with vulnerability for affective disorders,
including anxiety and depression. A recent functional
magnetic resonance imaging study suggested that this
association may be mediated by 5-HTTLPR effects on the
response bias of the human amygdala-a brain region critical
for emotional and social behavior-to environmental
threat.<h4>Objectives and design</h4>To examine the effects
of 5-HTTLPR genotype on the reactivity of the human amygdala
to salient environmental cues with functional magnetic
resonance imaging in a large (N = 92) cohort of volunteers
carefully screened for past and present medical or
psychiatric illness, and to explore the effects of 5-HTTLPR
genotype as well as amygdala reactivity on harm avoidance, a
putative personality measure related to trait
anxiety.<h4>Results</h4>We now confirm the finding of
5-HTTLPR short allele-driven amygdala hyperreactivity in a
large independent cohort of healthy subjects with no history
of psychiatric illness or treatment. Furthermore, we
demonstrate that these genotype effects on amygdala function
are consistent with a dominant short allele effect and are
equally prominent in men and women. However, neither
5-HTTLPR genotype, amygdala reactivity, nor genotype-driven
variability in this reactivity was reflected in harm
avoidance scores.<h4>Conclusions</h4>Our results reveal a
potent modulatory effect of the 5-HTTLPR on amygdala
reactivity to environmental threat. Since this genetically
driven effect exists in healthy subjects, it does not, in
and of itself, predict dimensions of mood or temperament. As
such, the 5-HTTLPR may represent a classic susceptibility
factor for affective disorders by biasing the functional
reactivity of the human amygdala in the context of stressful
life experiences and/or deficient cortical regulatory
input.},
Language = {eng},
Doi = {10.1001/archpsyc.62.2.146},
Key = {Hariri2005}
}
@article{Winterer2005,
Author = {Winterer, G and Hariri, AR and Goldman, D and Weinberger,
DR},
Title = {Neuroimaging and human genetics.},
Journal = {International review of neurobiology},
Volume = {67},
Pages = {325-383},
Address = {Genes, Cognition and Psychosis Program, National Institute
of Mental Health National Institutes of Health, Bethesda,
Maryland 20892, USA.},
Year = {2005},
Month = {January},
ISSN = {0074-7742},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16291027},
Keywords = {Brain/*anatomy \& histology/physiology • *Brain Mapping
• *Diagnostic Imaging • *Genetics • Genetics,
Medical • Humans},
Abstract = {The past few years have seen a rapid expansion of the
application of neuroimaging tools to the investigation of
the genetics of brain structure and function. In this
chapter, we will (1) highlight the most important steps
during the historical development of this research field,
(2) explain the major purposes of using neuroimaging in
genetic research, (3) address methodological issues that are
relevant with regard to the application of neuroimaging in
genetic research, (4) give an overview of the present
state-of-research, and (5) provide several examples of how
neuroimaging was successfully applied. © 2005 Elsevier Inc.
All rights reserved.},
Language = {eng},
Doi = {10.1016/s0074-7742(05)67010-9},
Key = {Winterer2005}
}
@article{Egan2004,
Author = {Egan, MF and Straub, RE and Goldberg, TE and Yakub, I and Callicott, JH and Hariri, AR and Mattay, VS and Bertolino, A and Hyde, TM and Shannon-Weickert, C and Akil, M and Crook, J and Vakkalanka, RK and Balkissoon, R and Gibbs, RA and Kleinman, JE and Weinberger,
DR},
Title = {Variation in GRM3 affects cognition, prefrontal glutamate,
and risk for schizophrenia.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {101},
Number = {34},
Pages = {12604-12609},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health/NIH/DHHS,
Building 10, Center Drive, Bethesda, MD 20892,
USA.},
Year = {2004},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15310849},
Keywords = {Adult • Cognition/*physiology • Genetic
Predisposition to Disease • Genotype •
Glutamates/*metabolism • Haplotypes •
Hippocampus/anatomy \& histology/metabolism • Humans
• Magnetic Resonance Imaging • Middle Aged •
Neuropsychological Tests • Phenotype • Prefrontal
Cortex/*metabolism • Receptors, Metabotropic
Glutamate/genetics/*metabolism • Schizophrenia/*metabolism
• Sequence Analysis, DNA},
Abstract = {GRM3, a metabotropic glutamate receptor-modulating synaptic
glutamate, is a promising schizophrenia candidate gene. In a
family-based association study, a common GRM3 haplotype was
strongly associated with schizophrenia (P = 0.0001). Within
this haplotype, the A allele of single-nucleotide
polymorphism (SNP) 4 (hCV11245618) in intron 2 was slightly
overtransmitted to probands (P = 0.02). We studied the
effects of this SNP on neurobiological traits related to
risk for schizophrenia and glutamate neurotransmission. The
SNP4 A allele was associated with poorer performance on
several cognitive tests of prefrontal and hippocampal
function. The physiological basis of this effect was
assessed with functional MRI, which showed relatively
deleterious activation patterns in both cortical regions in
control subjects homozygous for the SNP4 A allele. We next
looked at SNP4's effects on two indirect measures of
prefrontal glutamate neurotransmission. Prefrontal
N-acetylaspartate, an in vivo MRI measure related to
synaptic activity and closely correlated with tissue
glutamate, was lower in SNP4 AA homozygotes. In postmortem
human prefrontal cortex, AA homozygotes had lower mRNA
levels of the glial glutamate transporter EAAT2, a protein
regulated by GRM3 that critically modulates synaptic
glutamate. Effects of SNP4 on prefrontal GRM3 mRNA and
protein levels were marginal. Resequencing revealed no
missense or splice-site SNPs, suggesting that the intronic
SNP4 or related haplotypes may exert subtle regulatory
effects on GRM3 transcription. These convergent data point
to a specific molecular pathway by which GRM3 genotype
alters glutamate neurotransmission, prefrontal and
hippocampal physiology and cognition, and thereby increased
risk for schizophrenia.},
Language = {eng},
Doi = {10.1073/pnas.0405077101},
Key = {Egan2004}
}
@article{Wang2004,
Author = {Wang, AT and Dapretto, M and Hariri, AR and Sigman, M and Bookheimer,
SY},
Title = {Neural correlates of facial affect processing in children
and adolescents with autism spectrum disorder.},
Journal = {Journal of the American Academy of Child and Adolescent
Psychiatry},
Volume = {43},
Number = {4},
Pages = {481-490},
Address = {Department of Psychology, UCLA, Los Angeles, CA,
USA.},
Year = {2004},
Month = {April},
ISSN = {0890-8567},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15187809},
Keywords = {Adolescent • Amygdala/*physiopathology • Analysis
of Variance • Autistic Disorder/*physiopathology •
Brain Mapping • Case-Control Studies • Cerebral
Cortex/*physiopathology • Child • Emotions •
*Facial Expression • Humans • Magnetic Resonance
Imaging • Male • Psycholinguistics •
Regression Analysis • *Social Perception},
Abstract = {<h4>Objective</h4>To examine the neural basis of impairments
in interpreting facial emotions in children and adolescents
with autism spectrum disorders (ASD).<h4>Method</h4>Twelve
children and adolescents with ASD and 12 typically
developing (TD) controls matched faces by emotion and
assigned a label to facial expressions while undergoing
functional magnetic resonance imaging.<h4>Results</h4>Both
groups engaged similar neural networks during facial emotion
processing, including activity in the fusiform gyrus (FG)
and prefrontal cortex. However, between-group analyses in
regions of interest revealed that when matching facial
expressions, the ASD group showed significantly less
activity than the TD group in the FG, but reliably greater
activity in the precuneus. During the labeling of facial
emotions, no between-group differences were observed at the
behavioral or neural level. Furthermore, activity in the
amygdala was moderated by task demands in the TD group but
not in the ASD group.<h4>Conclusions</h4>These findings
suggest that children and adolescents with ASD in part
recruit different neural networks and rely on different
strategies when processing facial emotions. High-functioning
individuals with ASD may be relatively unimpaired in the
cognitive assessment of basic emotions, yet still show
differences in the automatic processing of facial
expressions.},
Language = {eng},
Doi = {10.1097/00004583-200404000-00015},
Key = {Wang2004}
}
@article{Holmes2003,
Author = {Holmes, A and Hariri, AR},
Title = {The serotonin transporter gene-linked polymorphism and
negative emotionality: placing single gene effects in the
context of genetic background and environment.},
Journal = {Genes, brain, and behavior},
Volume = {2},
Number = {6},
Pages = {332-335},
Year = {2003},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14653304},
Keywords = {Animals • Brain/physiopathology • Carrier
Proteins/*genetics • Disease Models, Animal •
Emotions/*physiology • Environment • Humans •
Membrane Glycoproteins/*genetics • *Membrane Transport
Proteins • Mice • Mood Disorders/*genetics •
*Nerve Tissue Proteins • Polymorphism,
Genetic/*physiology • Promoter Regions,
Genetic/*genetics • Serotonin • Serotonin Plasma
Membrane Transport Proteins},
Language = {eng},
Doi = {10.1046/j.1601-1848.2003.00052.x},
Key = {Holmes2003}
}
@article{Hariri2003b,
Author = {Hariri, AR and Weinberger, DR},
Title = {Functional neuroimaging of genetic variation in serotonergic
neurotransmission.},
Journal = {Genes, brain, and behavior},
Volume = {2},
Number = {6},
Pages = {341-349},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, US Department of Health and Human
Services, Bethesda, Maryland, USA. haririar@upmc.edu},
Year = {2003},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14653306},
Keywords = {Amygdala/*physiology • Animals • *Brain Mapping
• Fear/physiology • Genetic Variation •
Humans • *Magnetic Resonance Imaging • Nerve
Net/physiology • Neural Pathways/physiology •
Polymorphism, Genetic/*genetics • Serotonin/*genetics
• Synaptic Transmission/*genetics},
Abstract = {Serotonin (5-hydroxytryptamine; 5-HT) is a potent modulator
of the physiology and behavior involved in generating
appropriate responses to environmental cues such as danger
or threat. Furthermore, genetic variation in 5-HT subsystem
genes can impact upon several dimensions of emotional
behavior including neuroticism and psychopathology, but
especially anxiety traits. Recently, functional neuroimaging
has provided a dramatic illustration of how a promoter
polymorphism in the human 5-HT transporter (5-HTT) gene,
which has been weakly related to these behaviors, is
strongly related to the engagement of neural systems, namely
the amygdala, subserving emotional processes. In this
commentary, we discuss how functional neuroimaging can be
used to characterize the effects of polymorphisms in 5-HT
subsystem genes on the response of neural circuits
underlying the generation and regulation of mood and
temperament as well as susceptibility to affective illness.
We argue that in time, such knowledge will allow us to not
only transcend phenomenological diagnosis and represent
mechanisms of disease, but also identify at-risk individuals
and biological pathways for the development of new
treatments.},
Language = {eng},
Doi = {10.1046/j.1601-1848.2003.00048.x},
Key = {Hariri2003b}
}
@article{fds252120,
Author = {Hariri, AR and Goldberg, TE and Mattay, VS and Kolachana, BS and Callicott, JH and Egan, MF and Weinberger, DR},
Title = {Brain-derived neurotrophic factor val66met polymorphism
affects human memory-related hippocampal activity and
predicts memory performance.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {23},
Number = {17},
Pages = {6690-6694},
Year = {2003},
Month = {July},
Abstract = {BDNF plays a critical role in activity-dependent
neuroplasticity underlying learning and memory in the
hippocampus. A frequent single nucleotide polymorphism in
the targeting region of the human BDNF gene (val66met) has
been associated with abnormal intracellular trafficking and
regulated secretion of BDNF in cultured hippocampal neurons
transfected with the met allele. In addition, the met allele
has been associated with abnormal hippocampal neuronal
function as well as impaired episodic memory in human
subjects, but a direct effect of BDNF alleles on hippocampal
processing of memory has not been demonstrated. We studied
the relationship of the BDNF val66met genotype and
hippocampal activity during episodic memory processing using
blood oxygenation level-dependent functional magnetic
resonance imaging and a declarative memory task in healthy
individuals. Met carriers exhibited relatively diminished
hippocampal engagement in comparison with val homozygotes
during both encoding and retrieval processes. Remarkably,
the interaction between the BDNF val66met genotype and the
hippocampal response during encoding accounted for 25% of
the total variation in recognition memory performance. These
data implicate a specific genetic mechanism for substantial
normal variation in human declarative memory and suggest
that the basic effects of BDNF signaling on hippocampal
function in experimental animals are important in
humans.},
Doi = {10.1523/jneurosci.23-17-06690.2003},
Key = {fds252120}
}
@article{fds252077,
Author = {Mattay, VS and Goldberg, TE and Fera, F and Hariri, AR and Tessitore, A and Egan, MF and Kolachana, B and Callicott, JH and Weinberger,
DR},
Title = {Catechol O-methyltransferase val158-met genotype and
individual variation in the brain response to
amphetamine.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {100},
Number = {10},
Pages = {6186-6191},
Year = {2003},
Month = {May},
ISSN = {0027-8424},
Abstract = {Monamines subserve many critical roles in the brain, and
monoaminergic drugs such as amphetamine have a long history
in the treatment of neuropsychiatric disorders and also as a
substance of abuse. The clinical effects of amphetamine are
quite variable, from positive effects on mood and cognition
in some individuals, to negative responses in others,
perhaps related to individual variations in monaminergic
function and monoamine system genes. We explored the effect
of a functional polymorphism (val(158)-met) in the catechol
O-methyltransferase gene, which has been shown to modulate
prefrontal dopamine in animals and prefrontal cortical
function in humans, on the modulatory actions of amphetamine
on the prefrontal cortex. Amphetamine enhanced the
efficiency of prefrontal cortex function assayed with
functional MRI during a working memory task in subjects with
the high enzyme activity val/val genotype, who presumably
have relatively less prefrontal synaptic dopamine, at all
levels of task difficulty. In contrast, in subjects with the
low activity met/met genotype who tend to have superior
baseline prefrontal function, the drug had no effect on
cortical efficiency at low-to-moderate working memory load
and caused deterioration at high working memory load. These
data illustrate an application of functional neuroimaging in
pharmacogenomics and extend basic evidence of an
inverted-"U" functional-response curve to increasing
dopamine signaling in the prefrontal cortex. Further,
individuals with the met/met catechol O-methyltransferase
genotype appear to be at increased risk for an adverse
response to amphetamine.},
Doi = {10.1073/pnas.0931309100},
Key = {fds252077}
}
@article{Hariri2003c,
Author = {Hariri, AR and Mattay, VS and Tessitore, A and Fera, F and Weinberger,
DR},
Title = {Neocortical modulation of the amygdala response to fearful
stimuli.},
Journal = {Biological psychiatry},
Volume = {53},
Number = {6},
Pages = {494-501},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, Department of Health and Human
Services, Bethesda, Maryland 20892, USA.},
Year = {2003},
Month = {March},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12644354},
Keywords = {Adult • Affect • Amygdala/*anatomy \&
histology/*metabolism • Cognition/physiology •
Equipment Design • *Fear • Female • Galvanic
Skin Response/physiology • Humans • Magnetic
Resonance Imaging/instrumentation • Male •
Oxygen/blood • Photic Stimulation • Prefrontal
Cortex/*anatomy \& histology/*metabolism},
Abstract = {<h4>Background</h4>The cortical circuitry involved in
conscious cognitive processes and the subcortical circuitry
involved in fear responses have been extensively studied
with neuroimaging, but their interactions remain largely
unexplored. A recent functional magnetic resonance imaging
(fMRI) study demonstrated that the engagement of the right
prefrontal cortex during the cognitive evaluation of angry
and fearful facial expressions is associated with an
attenuation of the response of the amygdala to these same
stimuli, providing evidence for a functional neural network
for emotional regulation.<h4>Methods</h4>In the current
study, we have explored the generalizability of this
functional network by using threatening and fearful non-face
stimuli derived from the International Affective Picture
System (IAPS), as well as the influence of this network on
peripheral autonomic responses.<h4>Results</h4>Similar to
the earlier findings with facial expressions, blood oxygen
level dependent fMRI revealed that whereas perceptual
processing of IAPS stimuli was associated with a bilateral
amygdala response, cognitive evaluation of these same
stimuli was associated with attenuation of this amygdala
response and a correlated increase in response of the right
prefrontal cortex and the anterior cingulate cortex.
Moreover, this pattern was reflected in changes in skin
conductance.<h4>Conclusions</h4>The current results further
implicate the importance of neocortical regions, including
the prefrontal and anterior cingulate cortices, in
regulating emotional responses mediated by the amygdala
through conscious evaluation and appraisal.},
Language = {eng},
Doi = {10.1016/s0006-3223(02)01786-9},
Key = {Hariri2003c}
}
@article{Hariri2003a,
Author = {Hariri, AR and Weinberger, DR},
Title = {Imaging genomics.},
Journal = {British medical bulletin},
Volume = {65},
Pages = {259-270},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, Maryland 20892,
USA.},
Year = {2003},
Month = {January},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12697630},
Keywords = {Apolipoproteins E/genetics • Brain/*pathology •
Brain Diseases/*genetics/pathology • Carrier
Proteins/genetics • Catechol O-Methyltransferase/genetics
• *Genomics • Humans • *Magnetic Resonance
Imaging • Membrane Glycoproteins/genetics •
*Membrane Transport Proteins • *Nerve Tissue Proteins
• Polymorphism, Genetic • Serotonin Plasma
Membrane Transport Proteins},
Abstract = {The recent completion of a working draft of the human genome
sequence promises to provide unprecedented opportunities to
explore the genetic basis of individual differences in
complex behaviours and vulnerability to neuropsychiatric
illness. Functional neuroimaging, because of its unique
ability to assay information processing at the level of
brain within individuals, provides a powerful approach to
such functional genomics. Recent fMRI studies have
established important physiological links between functional
genetic polymorphisms and robust differences in information
processing within distinct brain regions and circuits that
have been linked to the manifestation of various disease
states such as Alzheimer's disease, schizophrenia and
anxiety disorders. Importantly, all of these biological
relationships have been revealed in relatively small samples
of healthy volunteers and in the absence of observable
differences at the level of behaviour, underscoring the
power of a direct assay of brain physiology like fMRI in
exploring the functional impact of genetic
variation.},
Language = {eng},
Doi = {10.1093/bmb/65.1.259},
Key = {Hariri2003a}
}
@article{Hariri2003d,
Author = {Hariri, A. R. and Goldberg, T. E. and Mattay, V. S. and Kolachana, B. S. and Callicott, J. H. and Egan, M. F. and Weinberger, D. R.},
Title = {Brain-derived neurotrophic factor val66met polymorphism
affects human memory-related hippocampal activity and
predicts memory performance},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {23},
Number = {17},
Pages = {6690--4},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, United States Department of Health and
Human Services, Bethesda, Maryland 20892-1384,
USA.},
Year = {2003},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12890761},
Keywords = {Adult • Amino Acid Substitution/*genetics •
Brain/anatomy \& histology/physiology • Brain Mapping
• Brain-Derived Neurotrophic Factor/*genetics •
Cohort Studies • DNA Mutational Analysis • Female
• Genotype • Heterozygote •
Hippocampus/anatomy \& histology/*physiology •
Homozygote • Humans • Magnetic Resonance Imaging
• Male • Memory/*physiology • Photic
Stimulation • Polymorphism, Genetic/*genetics •
Reference Values • Regression Analysis},
Abstract = {BDNF plays a critical role in activity-dependent
neuroplasticity underlying learning and memory in the
hippocampus. A frequent single nucleotide polymorphism in
the targeting region of the human BDNF gene (val66met) has
been associated with abnormal intracellular trafficking and
regulated secretion of BDNF in cultured hippocampal neurons
transfected with the met allele. In addition, the met allele
has been associated with abnormal hippocampal neuronal
function as well as impaired episodic memory in human
subjects, but a direct effect of BDNF alleles on hippocampal
processing of memory has not been demonstrated. We studied
the relationship of the BDNF val66met genotype and
hippocampal activity during episodic memory processing using
blood oxygenation level-dependent functional magnetic
resonance imaging and a declarative memory task in healthy
individuals. Met carriers exhibited relatively diminished
hippocampal engagement in comparison with val homozygotes
during both encoding and retrieval processes. Remarkably,
the interaction between the BDNF val66met genotype and the
hippocampal response during encoding accounted for 25\% of
the total variation in recognition memory performance. These
data implicate a specific genetic mechanism for substantial
normal variation in human declarative memory and suggest
that the basic effects of BDNF signaling on hippocampal
function in experimental animals are important in
humans.},
Language = {eng},
Key = {Hariri2003d}
}
@article{Mattay2003,
Author = {Mattay, V. S. and Goldberg, T. E. and Fera, F. and Hariri,
A. R. and Tessitore, A. and Egan, M. F. and Kolachana, B. and Callicott, J. H. and Weinberger, D. R.},
Title = {Catechol O-methyltransferase val158-met genotype and
individual variation in the brain response to
amphetamine},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {100},
Number = {10},
Pages = {6186--91},
Address = {Clinical Brain Disorders Branch, National Institute of
Mental Health, National Institutes of Health, Department of
Health and Human Services, Building 10, Center Drive, Room
4S-235, Bethesda, MD 20982-1379, USA.},
Year = {2003},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12716966},
Keywords = {Amino Acid Substitution • Brain/drug
effects/enzymology/*physiology • Catechol
O-Methyltransferase/*genetics • DNA/genetics/isolation
\& purification • Dextroamphetamine/*pharmacology
• Genotype • Humans • Magnetic Resonance
Imaging • Methionine • Organ Specificity •
Valine},
Abstract = {Monamines subserve many critical roles in the brain, and
monoaminergic drugs such as amphetamine have a long history
in the treatment of neuropsychiatric disorders and also as a
substance of abuse. The clinical effects of amphetamine are
quite variable, from positive effects on mood and cognition
in some individuals, to negative responses in others,
perhaps related to individual variations in monaminergic
function and monoamine system genes. We explored the effect
of a functional polymorphism (val(158)-met) in the catechol
O-methyltransferase gene, which has been shown to modulate
prefrontal dopamine in animals and prefrontal cortical
function in humans, on the modulatory actions of amphetamine
on the prefrontal cortex. Amphetamine enhanced the
efficiency of prefrontal cortex function assayed with
functional MRI during a working memory task in subjects with
the high enzyme activity val/val genotype, who presumably
have relatively less prefrontal synaptic dopamine, at all
levels of task difficulty. In contrast, in subjects with the
low activity met/met genotype who tend to have superior
baseline prefrontal function, the drug had no effect on
cortical efficiency at low-to-moderate working memory load
and caused deterioration at high working memory load. These
data illustrate an application of functional neuroimaging in
pharmacogenomics and extend basic evidence of an
inverted-``U'' functional-response curve to increasing
dopamine signaling in the prefrontal cortex. Further,
individuals with the met/met catechol O-methyltransferase
genotype appear to be at increased risk for an adverse
response to amphetamine.},
Language = {eng},
Doi = {10.1073/pnas.0931309100},
Key = {Mattay2003}
}
@article{fds251988,
Author = {Tessitore, A and Hariri, AR and Fera, F and Smith, WG and Chase, TN and Hyde, TM and Weinberger, DR and Mattay, VS},
Title = {Erratum: Dopamine modulates the response of the human
amygdala: A study in Parkinson's disease (Journal of
Neuroscience (October 15, 2002) (9099-9103))},
Journal = {Journal of Neuroscience},
Volume = {22},
Number = {24},
Pages = {i},
Year = {2002},
Month = {December},
Key = {fds251988}
}
@article{Hariri2002c,
Author = {Hariri, AR and Mattay, VS and Tessitore, A and Fera, F and Smith, WG and Weinberger, DR},
Title = {Dextroamphetamine modulates the response of the human
amygdala.},
Journal = {Neuropsychopharmacology : official publication of the
American College of Neuropsychopharmacology},
Volume = {27},
Number = {6},
Pages = {1036-1040},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD, USA.
hariria@intra.nimh.nih.gov},
Year = {2002},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12464460},
Keywords = {Adult • Amygdala/*drug effects/physiology •
Dextroamphetamine/*pharmacology • Double-Blind Method
• Emotions/*drug effects/physiology • Facial
Expression • Female • Humans • Magnetic
Resonance Imaging/methods/statistics \& numerical data
• Male},
Abstract = {Amphetamine, a potent monoaminergic agonist, has pronounced
effects on emotional behavior in humans, including the
generation of fear and anxiety. Recent animal studies have
demonstrated the importance of monoamines, especially
dopamine, in modulating the response of the amygdala, a key
brain region involved in the perception of fearful and
threatening stimuli, and the generation of appropriate
physiological and behavioral responses. We have explored the
possibility that the anxiogenic effect of amphetamine in
humans reflects the drug's influence on the activity of the
amygdala. In a double-blind placebo controlled study, fMRI
revealed that dextroamphetamine potentiated the response of
the amygdala during the perceptual processing of angry and
fearful facial expressions. Our results provide the first
evidence of a specific neural substrate for the anxiogenic
effects of amphetamine and are consistent with animal models
of dopaminergic activation of the amygdala.},
Language = {eng},
Doi = {10.1016/s0893-133x(02)00373-1},
Key = {Hariri2002c}
}
@article{Tessitore2002,
Author = {Tessitore, A and Hariri, AR and Fera, F and Smith, WG and Chase, TN and Hyde, TM and Weinberger, DR and Mattay, VS},
Title = {Dopamine modulates the response of the human amygdala: a
study in Parkinson's disease.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {22},
Number = {20},
Pages = {9099-9103},
Address = {Clinical Brain Disorders Branch, National Institute of
Mental Health, National Institutes of Health, Bethesda,
Maryland 20892-1384, USA.},
Year = {2002},
Month = {October},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12388617},
Keywords = {Amygdala/drug effects/*physiopathology • Antiparkinson
Agents/therapeutic use • Behavior • Brain Mapping
• Dopamine/*metabolism/pharmacology • Dopamine
Agonists/therapeutic use • Drug Therapy, Combination
• Emotions/physiology • Facial Expression •
Female • Humans • Magnetic Resonance Imaging
• Male • Middle Aged • Parkinson
Disease/*physiopathology • Pattern Recognition, Visual
• Photic Stimulation • Reaction Time •
Reference Values},
Abstract = {In addition to classic motor signs and symptoms, Parkinson's
disease (PD) is characterized by neuropsychological and
emotional deficits, including a blunted emotional response.
In the present study, we explored both the neural basis of
abnormal emotional behavior in PD and the physiological
effects of dopaminergic therapy on the response of the
amygdala, a central structure in emotion processing. PD
patients and matched normal controls (NCs) were studied with
blood oxygenation level-dependent functional magnetic
resonance imaging during a paradigm that involved perceptual
processing of fearful stimuli. PD patients were studied
twice, once during a relatively hypodopaminergic state
(i.e., > or =12 hr after their last dose of dopamimetic
treatment) and again during a dopamine-replete state. The
imaging data revealed a robust bilateral amygdala response
in NCs that was absent in PD patients during the
hypodopaminergic state. Dopamine repletion partially
restored this response in PD patients. Our results
demonstrate an abnormal amygdala response in PD that may
underlie the emotional deficits accompanying the disease.
Furthermore, consistent with findings in experimental animal
paradigms, our results provide in vivo evidence of the role
of dopamine in modulating the response of the amygdala to
sensory information in human subjects.},
Language = {eng},
Doi = {10.1523/jneurosci.22-20-09099.2002},
Key = {Tessitore2002}
}
@article{Hariri2002a,
Author = {Hariri, AR and Tessitore, A and Mattay, VS and Fera, F and Weinberger,
DR},
Title = {The amygdala response to emotional stimuli: a comparison of
faces and scenes.},
Journal = {NeuroImage},
Volume = {17},
Number = {1},
Pages = {317-323},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, Maryland 20892, USA.
hariria@intra.nimh.nih.gov},
Year = {2002},
Month = {September},
ISSN = {1053-8119},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12482086},
Keywords = {Adult • Amygdala/anatomy \& histology/*physiology
• Anger/physiology • Emotions/*physiology •
*Facial Expression • Fear/physiology • Female
• Galvanic Skin Response/physiology • Humans
• Image Interpretation, Computer-Assisted •
Individuality • Magnetic Resonance Imaging • Male
• Reaction Time/physiology • Social
Perception},
Abstract = {As a central fear processor of the brain, the amygdala
initiates a cascade of critical physiological and behavioral
responses. Neuroimaging studies have shown that the human
amygdala responds not only to fearful and angry facial
expressions but also to fearful and threatening scenes such
as attacks, explosions, and mutilations. Given the relative
importance of facial expressions in adaptive social
behavior, we hypothesized that the human amygdala would
exhibit a stronger response to angry and fearful facial
expressions in comparison to other fearful and threatening
stimuli. Twelve subjects completed two tasks while
undergoing fMRI: matching angry or fearful facial
expressions, and matching scenes depicting fearful or
threatening situations derived from the International
Affective Picture System (IAPS). While there was an amygdala
response to both facial expressions and IAPS stimuli, direct
comparison revealed that the amygdala response to facial
expressions was significantly greater than that to IAPS
stimuli. Autonomic reactivity, measured by skin conductance
responses, was also greater to facial expressions. These
results suggest that the human amygdala shows a stronger
response to affective facial expressions than to scenes, a
bias that should be considered in the design of experimental
paradigms interested in probing amygdala
function.},
Language = {eng},
Doi = {10.1006/nimg.2002.1179},
Key = {Hariri2002a}
}
@article{Hariri2002b,
Author = {Hariri, AR and Mattay, VS and Tessitore, A and Kolachana, B and Fera, F and Goldman, D and Egan, MF and Weinberger, DR},
Title = {Serotonin transporter genetic variation and the response of
the human amygdala.},
Journal = {Science (New York, N.Y.)},
Volume = {297},
Number = {5580},
Pages = {400-403},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD 20892,
USA.},
Year = {2002},
Month = {July},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12130784},
Keywords = {Adult • Alleles • Amygdala/*physiology •
Carrier Proteins/*genetics/physiology • Cohort Studies
• Facial Expression • *Fear • Female •
Functional Laterality • *Genetic Variation •
Genotype • Humans • Magnetic Resonance Imaging
• Male • Membrane Glycoproteins/*genetics/physiology
• *Membrane Transport Proteins • *Nerve Tissue
Proteins • Personality • Polymorphism, Genetic
• *Promoter Regions, Genetic •
Serotonin/*metabolism • Serotonin Plasma Membrane
Transport Proteins • Sex Characteristics},
Abstract = {A functional polymorphism in the promoter region of the
human serotonin transporter gene (SLC6A4) has been
associated with several dimensions of neuroticism and
psychopathology, especially anxiety traits, but the
predictive value of this genotype against these complex
behaviors has been inconsistent. Serotonin [5-
hydroxytryptamine, (5-HT)] function influences normal fear
as well as pathological anxiety, behaviors critically
dependent on the amygdala in animal models and in clinical
studies. We now report that individuals with one or two
copies of the short allele of the serotonin transporter
(5-HTT) promoter polymorphism, which has been associated
with reduced 5-HTT expression and function and increased
fear and anxiety-related behaviors, exhibit greater amygdala
neuronal activity, as assessed by BOLD functional magnetic
resonance imaging, in response to fearful stimuli compared
with individuals homozygous for the long allele. These
results demonstrate genetically driven variation in the
response of brain regions underlying human emotional
behavior and suggest that differential excitability of the
amygdala to emotional stimuli may contribute to the
increased fear and anxiety typically associated with the
short SLC6A4 allele.},
Language = {eng},
Doi = {10.1126/science.1071829},
Key = {Hariri2002b}
}
@article{Mattay2002,
Author = {Mattay, VS and Fera, F and Tessitore, A and Hariri, AR and Das, S and Callicott, JH and Weinberger, DR},
Title = {Neurophysiological correlates of age-related changes in
human motor function.},
Journal = {Neurology},
Volume = {58},
Number = {4},
Pages = {630-635},
Address = {Clinical Brain Disorders Branch, Intramural Research
Program, National Institute of Mental Health, NIH, Bethesda,
MD 20892-1379, USA. vsm@helix.nih.gov},
Year = {2002},
Month = {February},
ISSN = {0028-3878},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11865144},
Keywords = {Adult • Aging/*physiology • Analysis of Variance
• Brain/*physiology • Female • Humans •
Magnetic Resonance Imaging/statistics \& numerical data
• Male • Middle Aged • Psychomotor
Performance/*physiology},
Abstract = {<h4>Background</h4>There are well-defined and characteristic
age-related deficits in motor abilities that may reflect
structural and chemical changes in the aging
brain.<h4>Objective</h4>To delineate age-related changes in
the physiology of brain systems subserving simple motor
behavior.<h4>Methods</h4>Ten strongly right-handed young
(<35 years of age) and 12 strongly right-handed elderly (>50
years of age) subjects with no evidence of cognitive or
motor deficits participated in the study. Whole-brain
functional imaging was performed on a 1.5-T MRI scanner
using a spiral pulse sequence while the subjects performed a
visually paced "button-press" motor task with their dominant
right hand alternating with a rest state.<h4>Results</h4>Although
the groups did not differ in accuracy, there was an increase
in reaction time in the elderly subjects (mean score plus
minus SD, young subjects = 547 +/- 97 ms, elderly subjects =
794 +/- 280 ms, p < 0.03). There was a greater extent of
activation in the contralateral sensorimotor cortex, lateral
premotor area, supplementary motor area, and ipsilateral
cerebellum in the elderly subjects relative to the young
subjects (p < 0.001). Additional areas of activation, absent
in the young subjects, were seen in the ipsilateral
sensorimotor cortex, putamen (left > right), and
contralateral cerebellum of the elderly subjects.<h4>Conclusions</h4>The
results of this study show that elderly subjects recruit
additional cortical and subcortical areas even for the
performance of a simple motor task. These changes may
represent compensatory mechanisms invoked by the aging
brain, such as reorganization and redistribution of
functional networks to compensate for age-related structural
and neurochemical changes.},
Language = {eng},
Doi = {10.1212/wnl.58.4.630},
Key = {Mattay2002}
}
@article{fds252009,
Author = {Hariri, A and Sigman, M and Bookheimer, S},
Title = {Abnormal regional brain activity associated with processing
emotional stimuli in autistic subjects},
Journal = {NeuroImage},
Volume = {11},
Number = {5 PART II},
Pages = {S242},
Year = {2000},
Month = {January},
Doi = {10.1016/s1053-8119(00)91174-1},
Key = {fds252009}
}
@article{Hariri2000,
Author = {Hariri, AR and Bookheimer, SY and Mazziotta, JC},
Title = {Modulating emotional responses: effects of a neocortical
network on the limbic system.},
Journal = {Neuroreport},
Volume = {11},
Number = {1},
Pages = {43-48},
Address = {Brain Mapping Division, UCLA School of Medicine,
Ahmanson-Lovelace Brain Mapping Center 90095,
USA.},
Year = {2000},
Month = {January},
ISSN = {0959-4965},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10683827},
Keywords = {Adult • Amygdala/blood supply/physiology •
Anger/physiology • Cerebrovascular Circulation/physiology
• Emotions/*physiology • Facial Expression •
Fear/physiology • Female • Humans • Image
Interpretation, Computer-Assisted • Limbic System/blood
supply/*physiology • Magnetic Resonance Imaging •
Male • Neocortex/blood supply/*physiology • Nerve
Net/*physiology • Social Perception},
Abstract = {Humans share with animals a primitive neural system for
processing emotions such as fear and anger. Unlike other
animals, humans have the unique ability to control and
modulate instinctive emotional reactions through
intellectual processes such as reasoning, rationalizing, and
labeling our experiences. This study used functional MRI to
identify the neural networks underlying this ability.
Subjects either matched the affect of one of two faces to
that of a simultaneously presented target face (a perceptual
task) or identified the affect of a target face by choosing
one of two simultaneously presented linguistic labels (an
intellectual task). Matching angry or frightened expressions
was associated with increased regional cerebral blood flow
(rCBF) in the left and right amygdala, the brain's primary
fear centers. Labeling these same expressions was associated
with a diminished rCBF response in the amygdalae. This
decrease correlated with a simultaneous increase in rCBF in
the right prefrontal cortex, a neocortical region implicated
in regulating emotional responses. These results provide
evidence for a network in which higher regions attenuate
emotional responses at the most fundamental levels in the
brain and suggest a neural basis for modulating emotional
experience through interpretation and labeling.},
Language = {eng},
Doi = {10.1097/00001756-200001170-00009},
Key = {Hariri2000}
}
@article{Hale2000,
Author = {Hale, TS and Hariri, AR and McCracken, JT},
Title = {Attention-deficit/hyperactivity disorder: perspectives from
neuroimaging},
Journal = {Mental retardation and developmental disabilities research
reviews},
Volume = {6},
Number = {3},
Pages = {214-219},
Address = {UCLA School of Medicine, Los Angeles, California 90024,
USA.},
Year = {2000},
ISSN = {1080-4013},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10982499},
Keywords = {Attention Deficit Disorder with Hyperactivity/*pathology/physiopathology
• Brain/*pathology/radiography/radionuclide imaging
• Electroencephalography • Humans • Magnetic
Resonance Imaging • Tomography, Emission-Computed,
Single-Photon • Tomography, X-Ray Computed},
Abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common
childhood behavioral disorder most often characterized by
inattentiveness, impulsivity, and hyperactivity. Current
etiologic theories suggest that ADHD stems from
abnormalities in dopaminergic and possibly noradrenergic
brainstem nuclei that act to regulate a cortico-striato-thalamo-cortical
network, believed to be critical for executive functions and
the regulation of behavioral responses such as arousal,
attention, and inhibition. Noninvasive structural and
functional neuroimaging techniques provide a new avenue for
exploring the validity of these theories. Despite their
limitations, neuroimaging studies have provided a unique and
otherwise inaccessible, biological perspective of ADHD.
Collectively, the studies reviewed here reveal that
dysfunction in arousal, behavioral inhibition, and attention
associated with ADHD may result from structural
abnormalities in frontostriatal regions that in turn result
in diminished activity essential for normal
function.},
Language = {eng},
Doi = {10.1002/1098-2779(2000)6:33.0.CO;2-M},
Key = {Hale2000}
}
@article{fds252007,
Author = {Dapretto, M and Hariri, A and Bialik, MH and Bookheimer,
SY},
Title = {Cortical correlates of affective vs. linguistic prosody: An
fMRI study},
Journal = {NeuroImage},
Volume = {9},
Number = {6 PART II},
Pages = {S1054},
Year = {1999},
Month = {December},
ISSN = {1053-8119},
Key = {fds252007}
}
@article{fds252008,
Author = {Hariri, A and Quintana, J and Kovalik, E and Bookheimer,
S},
Title = {Processing of facial affect in schizophrenics: An fMRI
study},
Journal = {NeuroImage},
Volume = {9},
Number = {6 PART II},
Pages = {S647},
Year = {1999},
Month = {December},
ISSN = {1053-8119},
Key = {fds252008}
}
@article{fds252006,
Author = {Hariri, AR and Werren, JH and Wilkinson, GS},
Title = {Distribution and reproductive effects of Wolbachia in
stalk-eyed flies (Diptera: Diopsidae)},
Journal = {Heredity},
Volume = {81},
Number = {3},
Pages = {254-260},
Publisher = {Springer Nature America, Inc},
Year = {1998},
Month = {September},
Abstract = {Wolbachia are cytoplasmically inherited bacteria capable of
altering the reproductive biology of their hosts in a manner
which increases their spread within a population. These
microbes can cause cytoplasmic incompatibility,
parthenogenesis and feminization of genetic males. Because
Wolbachia have been associated with female-biased sex ratio
distortion, we used a PCR assay to examine 17 species of
stalk-eyed flies (Diptera: Diopsidae), two of which exhibit
female-biased sex ratios, for the presence of these
microbes. Type A Wolbachia was detected in four diopsid
species, three from the genus Sphyracephala, none of which
exhibit biased progeny sex ratios. The reproductive effects
of the microbe were examined in one of those species, S.
beccarii, by conducting reciprocal crosses between infected
and uninfected strains. In this species, Wolbachia do not
cause detectable cytoplasmic incompatibility or reduce host
fecundity. In contrast, our results are consistent with an
association between the microbes and enhanced male
fertility. Possible explanations for the pattern of
distribution and effects on male fertility include a
predisposition for acquiring Type A Wolbachia by these flies
and accommodation by the host genome to bacterial
presence.},
Doi = {10.1038/sj.hdy.6883640},
Key = {fds252006}
}
@article{fds252005,
Author = {Bookheimer, SY and Zeineh, MM and Strojwas, MH and Hariri,
AR},
Title = {Localization of memory-related activation on a picture
priming task using fMRI},
Journal = {NeuroImage},
Volume = {7},
Number = {4 PART II},
Pages = {S824},
Year = {1998},
Month = {January},
Doi = {10.1016/s1053-8119(18)31657-4},
Key = {fds252005}
}