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| Publications of Maxwell Elliott :chronological by type listing:
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@article{fds340304,
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},
url = {http://dx.doi.org/10.1016/j.biopsych.2018.03.012},
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 = {fds340304}
}
@article{fds350927,
Author = {Elliott, M and Romer, A and Knodt, A and Hariri, A},
Title = {A Connectome Wide Functional Signature of Transdiagnostic
Risk for Mental Illness},
Year = {2017},
Month = {September},
url = {http://dx.doi.org/10.1101/196220},
Abstract = {<h4>Background</h4> 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. <h4>Methods</h4> 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). <h4>Results</h4> 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. <h4>Conclusions</h4> 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 = {10.1101/196220},
Key = {fds350927}
}
@article{fds358354,
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},
url = {http://dx.doi.org/10.1177/21677026211030240},
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 = {fds358354}
}
@article{fds358356,
Author = {Elliott, M},
Title = {A Data-Driven Exploration of the Functional Connectome in
Williams Syndrome},
Journal = {Biological Psychiatry},
Volume = {79},
Number = {9},
Pages = {216S-217S},
Year = {2016},
Month = {May},
Key = {fds358356}
}
@article{fds350917,
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},
url = {http://dx.doi.org/10.1002/hbm.24639},
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 = {fds350917}
}
@article{fds350925,
Author = {Elliott, M and Belsky, D and Anderson, K and Corcoran, D and Ge, T and Knodt, A and Prinz, J and Sugden, K and Williams, B and Ireland, D and Poulton, R and Caspi, A and Holmes, A and Moffitt, T and Hariri,
A},
Title = {A Polygenic Score for Higher Educational Attainment is
Associated with Larger Brains},
Year = {2018},
Month = {March},
url = {http://dx.doi.org/10.1101/287490},
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 development of larger brains. We tested
this hypothesis with molecular genetic data using
discoveries from a genome-wide association study (GWAS) of
educational attainment, a correlate of intelligence. We
analyzed genetic, brain imaging, and cognitive test data
from the UK Biobank, the Dunedin Study, the Brain Genomics
Superstruct Project (GSP), and the Duke Neurogenetics Study
(DNS) (combined N=8,271). We measured genetics using
polygenic scores based on published GWAS. 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 UK Biobank and Dunedin samples than in the
GSP and DNS samples. Sensitivity analysis suggested this
effect-size difference partly reflected restricted range of
cognitive performance in the GSP and DNS 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 data to understand
neurobiology linking genetics with individual differences in
cognitive performance.},
Doi = {10.1101/287490},
Key = {fds350925}
}
@article{fds350919,
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},
url = {http://dx.doi.org/10.1093/cercor/bhy219},
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 = {fds350919}
}
@article{fds351245,
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},
url = {http://dx.doi.org/10.1093/gerona/glaa178},
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 = {fds351245}
}
@article{fds353274,
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},
url = {http://dx.doi.org/10.1001/jama.2020.19998},
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 = {fds353274}
}
@article{fds350915,
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 Network Open},
Volume = {2},
Number = {10},
Pages = {e1913123},
Year = {2019},
Month = {October},
url = {http://dx.doi.org/10.1001/jamanetworkopen.2019.13123},
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 = {fds350915}
}
@article{fds363998,
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},
Pages = {10.1212/WNL.0000000000200898},
Year = {2022},
Month = {July},
url = {http://dx.doi.org/10.1212/wnl.0000000000200898},
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 three
'generations' of DNA methylation age algorithms
(1<sup>st</sup> generation: Horvath and Hannum clocks; 2nd
generation: PhenoAge and GrimAge; and 3<sup>rd</sup>
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 AD/ADRD screening
tests (Alzheimer's Disease Assessment Scale; Mini-Mental
State Examination; Montreal Cognitive Assessment); and
scores on cognitive tests (Rey Auditory Verbal Learning
Test; Logical Memory Test; Trail Making Test). In an
independent replication in the FHS Offspring Cohort, we
further tested the longitudinal association between the DNA
methylation algorithms and risk of developing
dementia.<h4>Results</h4>In ADNI (<i>N</i> = 649
individuals), the 1<sup>st</sup> generation (Horvath and
Hannum DNA methylation age clocks) and the 2<sup>nd</sup>
generation (PhenoAge and GrimAge) DNA methylation measures
of aging were not consistently associated with measures of
cognitive impairment in older adults. In contrast, a
3<sup>rd</sup> generation measure of biological aging,
DunedinPACE, was associated with clinical diagnosis of
Alzheimer's Disease (beta[95%CI]=0.28[0.08-0.47]) and with
poorer scores on AD/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, HR[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, in their risk for
cognitive decline, and for evaluating interventions to slow
aging.},
Doi = {10.1212/wnl.0000000000200898},
Key = {fds363998}
}
@article{fds350913,
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},
url = {http://dx.doi.org/10.1038/s41380-019-0626-7},
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 = {fds350913}
}
@article{fds350918,
Author = {Elliott, M and Belsky, D and Knodt, A and Ireland, D and Melzer, T and Poulton, R and Ramrakha, S and Caspi, A and Moffitt, T and Hariri,
A},
Title = {Brain-age in midlife is associated with accelerated
biological aging and cognitive decline in a longitudinal
birth-cohort},
Year = {2019},
Month = {July},
url = {http://dx.doi.org/10.1101/712851},
Abstract = {An individual’s brain-age is the difference between
chronological age and age predicted from machine-learning
models of brain-imaging data. Brain-age has been proposed as
a biomarker of age-related deterioration of the brain.
Having an older brain-age 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 brain-age a biomarker of accelerated brain
aging, a study is needed of a large cohort all born the same
year who nevertheless vary on brain-age. In a
population-representative 1972-73 birth cohort we measured
brain-age at age 45, 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, brain-age was measured reliably (ICC=.81) and ranged
from 24 to 72 years. Those with older midlife brain-ages
tended to have poorer cognitive function in both adulthood
and childhood, as well as impaired brain health at age 3.
Furthermore, those with older brain-ages 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 brain-age as a potential surrogate
biomarker for midlife intervention studies that seek to
measure treatment response to dementia-prevention efforts in
midlife. However, the findings also caution against the
assumption that brain-age scores represent only age-related
deterioration of the brain as they may also index central
nervous system variation present since childhood.},
Doi = {10.1101/712851},
Key = {fds350918}
}
@article{fds354592,
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},
url = {http://dx.doi.org/10.1073/pnas.2010211118},
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 = {fds354592}
}
@article{fds358355,
Author = {Gregory, M and Eisenberg, D and Elliott, M and Czarapata, J and Hegarty,
C and Ianni, A and Kohn, P and Apud, J and Berman, K},
Title = {Connectome-Wide Association of Resting fMRI With Dopamine
Functioning in Patients With Schizophrenia and Healthy
Adults},
Journal = {Neuropsychopharmacology},
Volume = {41},
Pages = {S224-S225},
Year = {2016},
Month = {December},
Key = {fds358355}
}
@article{fds355829,
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},
url = {http://dx.doi.org/10.1038/s43587-021-00044-4},
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 = {fds355829}
}
@article{fds350911,
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},
url = {http://dx.doi.org/10.1002/brb3.1493},
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 = {fds350911}
}
@article{fds350924,
Author = {Elliott, M and Knodt, A and Cooke, M and Kim, J and Melzer, T and Keenan,
R and Ireland, D and Ramrakha, S and Poulton, R and Caspi, A and Moffitt,
T and Hariri, A},
Title = {General Functional Connectivity: shared features of
resting-state and task fMRI drive reliable and heritable
individual differences in functional brain
networks},
Year = {2018},
Month = {May},
url = {http://dx.doi.org/10.1101/330530},
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 displays higher heritability on average than
resting-state functional connectivity. We also show that
predictions of cognitive ability from GFC generalize 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 = {10.1101/330530},
Key = {fds350924}
}
@article{fds341341,
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},
url = {http://dx.doi.org/10.1016/j.neuroimage.2019.01.068},
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 = {fds341341}
}
@article{fds350912,
Author = {Reuben, A and Elliott, M and Caspi, A},
Title = {Implications of legacy lead for children's brain
development.},
Journal = {Nature Medicine},
Volume = {26},
Number = {1},
Pages = {23-25},
Year = {2020},
Month = {January},
url = {http://dx.doi.org/10.1038/s41591-019-0731-9},
Doi = {10.1038/s41591-019-0731-9},
Key = {fds350912}
}
@article{fds356133,
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},
url = {http://dx.doi.org/10.1016/j.biopsych.2021.02.971},
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 = {fds356133}
}
@article{fds350910,
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},
url = {http://dx.doi.org/10.1001/jamanetworkopen.2020.3221},
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 = {fds350910}
}
@article{fds350921,
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},
url = {http://dx.doi.org/10.1002/ab.21820},
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 2 = 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 = {fds350921}
}
@article{fds356036,
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},
url = {http://dx.doi.org/10.3389/fnagi.2021.652575},
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 = {fds356036}
}
@article{fds350908,
Author = {Elliott, ML},
Title = {MRI-based biomarkers of accelerated aging and dementia risk
in midlife: how close are we?},
Journal = {Ageing Research Reviews},
Volume = {61},
Pages = {101075},
Year = {2020},
Month = {August},
url = {http://dx.doi.org/10.1016/j.arr.2020.101075},
Abstract = {The global population is aging, leading to an increasing
burden of age-related neurodegenerative disease. Efforts to
intervene against age-related dementias in older adults have
generally proven ineffective. These failures suggest that a
lifetime of brain aging may be difficult to reverse once
widespread deterioration has occurred. To test interventions
in younger populations, biomarkers of brain aging are needed
that index subtle signs of accelerated brain deterioration
that are part of the putative pathway to dementia. Here I
review potential MRI-based biomarkers that could connect
midlife brain aging to later life dementia. I survey the
literature with three questions in mind, 1) Does the
biomarker index age-related changes across the lifespan? 2)
Does the biomarker index cognitive ability and cognitive
decline? 3) Is the biomarker sensitive to known risk factors
for dementia? I find that while there is preliminary support
for some midlife MRI-based biomarkers for accelerated aging,
the longitudinal research that would best answer these
questions is still in its infancy and needs to be further
developed. I conclude with suggestions for future
research.},
Doi = {10.1016/j.arr.2020.101075},
Key = {fds350908}
}
@article{fds355447,
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},
url = {http://dx.doi.org/10.1177/0956797621996665},
Doi = {10.1177/0956797621996665},
Key = {fds355447}
}
@article{fds350916,
Author = {Romer, A and Elliott, M and Knodt, A and Sison, M and Ireland, D and Houts,
R and Ramrakha, S and Poulton, R and Keenan, R and Melzer, T and Moffitt,
T and Caspi, A and Hariri, A},
Title = {Pervasively thinner neocortex as a transdiagnostic feature
of general psychopathology},
Year = {2019},
Month = {September},
url = {http://dx.doi.org/10.1101/788232},
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 p factor. We 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 p 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 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 p 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 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, the continued pursuit of which
may limit progress toward more effective strategies for
etiological understanding, prevention, and
intervention.},
Doi = {10.1101/788232},
Key = {fds350916}
}
@article{fds355563,
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},
url = {http://dx.doi.org/10.1176/appi.ajp.2020.19090934},
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 = {fds355563}
}
@article{fds350923,
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},
url = {http://dx.doi.org/10.1016/j.biopsych.2017.11.010},
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 = {fds350923}
}
@article{fds350926,
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},
url = {http://dx.doi.org/10.1523/jneurosci.1734-17.2017},
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 = {fds350926}
}
@article{fds350928,
Author = {Beim, JA and Elliott, M and Oxenham, AJ and Wojtczak,
M},
Title = {Stimulus Frequency Otoacoustic Emissions Provide No Evidence
for the Role of Efferents in the Enhancement
Effect.},
Journal = {Journal of the Association for Research in Otolaryngology :
Jaro},
Volume = {16},
Number = {5},
Pages = {613-629},
Year = {2015},
Month = {October},
url = {http://dx.doi.org/10.1007/s10162-015-0534-8},
Abstract = {Auditory enhancement refers to the perceptual phenomenon
that a target sound is heard out more readily from a
background sound if the background is presented alone first.
Here we used stimulus-frequency otoacoustic emissions
(SFOAEs) to test the hypothesis that activation of the
medial olivocochlear efferent system contributes to auditory
enhancement effects. The SFOAEs were used as a tool to
measure changes in cochlear responses to a target component
and the neighboring components of a multitone background
between conditions producing enhancement and conditions
producing no enhancement. In the "enhancement" condition,
the target and multitone background were preceded by a
precursor stimulus with a spectral notch around the signal
frequency; in the control (no-enhancement) condition, the
target and multitone background were presented without the
precursor. In an experiment using a wideband multitone
stimulus known to produce significant psychophysical
enhancement effects, SFOAEs showed no changes consistent
with enhancement, but some aspects of the results indicated
possible contamination of the SFOAE magnitudes by the
activation of the middle-ear-muscle reflex. The same SFOAE
measurements performed using narrower-band stimuli at lower
sound levels also showed no SFOAE changes consistent with
either absolute or relative enhancement despite robust
psychophysical enhancement effects observed in the same
listeners with the same stimuli. The results suggest that
cochlear efferent control does not play a significant role
in auditory enhancement effects.},
Doi = {10.1007/s10162-015-0534-8},
Key = {fds350928}
}
@article{fds357566,
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},
url = {http://dx.doi.org/10.1016/j.tics.2021.05.008},
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 = {fds357566}
}
@article{fds350920,
Author = {Elliott, M and Knodt, A and Ireland, D and Morris, M and Poulton, R and Ramrakha, S and Sison, M and Moffitt, T and Caspi, A and Hariri,
A},
Title = {What is the test-retest reliability of common task-fMRI
measures? New empirical evidence and a meta-analysis},
Year = {2019},
Month = {June},
url = {http://dx.doi.org/10.1101/681700},
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-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 (N=1,008)
revealed poor overall reliability (mean ICC=.397). Second,
the test-retest reliabilities of activity in a priori
regions of interest across 11 common fMRI tasks collected in
the context of the Human Connectome Project (N=45) and the
Dunedin Study (N=20) were poor (ICCs=.067-.485).
Collectively, these findings demonstrate that common
task-fMRI measures are not currently suitable for brain
biomarker discovery or individual differences research. We
review how this state of affairs came to be and highlight
avenues for improving task-fMRI reliability.},
Doi = {10.1101/681700},
Key = {fds350920}
}
@article{fds350909,
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},
url = {http://dx.doi.org/10.1177/0956797620916786},
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 = {fds350909}
}
@article{fds350922,
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},
url = {http://dx.doi.org/10.1093/braincomms/fcz041},
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 T2-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 (ß = -0.08, P = 0.013) and adult IQ
(ß=-0.15, P < 0.001). Moreover, white matter
hyperintensity volume was associated with greater cognitive
decline from childhood to midlife (ß=-0.09, P < 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 = {fds350922}
}
@article{fds350914,
Author = {Gregory, MD and Mervis, CB and Elliott, ML and Kippenhan, JS and Nash,
T and B Czarapata and J and Prabhakaran, R and Roe, K and Eisenberg, DP and Kohn, PD and Berman, KF},
Title = {Williams syndrome hemideletion and LIMK1 variation both
affect dorsal stream functional connectivity.},
Journal = {Brain},
Volume = {142},
Number = {12},
Pages = {3963-3974},
Year = {2019},
Month = {December},
url = {http://dx.doi.org/10.1093/brain/awz323},
Abstract = {Williams syndrome is a rare genetic disorder caused by
hemizygous deletion of ∼1.6 Mb affecting 26 genes on
chromosome 7 (7q11.23) and is clinically typified by two
cognitive/behavioural hallmarks: marked visuospatial
deficits relative to verbal and non-verbal reasoning
abilities and hypersocial personality. Clear knowledge of
the circumscribed set of genes that are affected in Williams
syndrome, along with the well-characterized neurobehavioural
phenotype, offers the potential to elucidate neurogenetic
principles that may apply in genetically and clinically more
complex settings. The intraparietal sulcus, in the dorsal
visual processing stream, has been shown to be structurally
and functionally altered in Williams syndrome, providing a
target for investigating resting-state functional
connectivity and effects of specific genes hemideleted in
Williams syndrome. Here, we tested for effects of the LIMK1
gene, deleted in Williams syndrome and important for
neuronal maturation and migration, on intraparietal sulcus
functional connectivity. We first defined a target brain
phenotype by comparing intraparietal sulcus resting
functional connectivity in individuals with Williams
syndrome, in whom LIMK1 is hemideleted, with typically
developing children. Then in two separate cohorts from the
general population, we asked whether intraparietal sulcus
functional connectivity patterns similar to those found in
Williams syndrome were associated with sequence variation of
the LIMK1 gene. Four independent between-group comparisons
of resting-state functional MRI data (total n = 510) were
performed: (i) 20 children with Williams syndrome compared
to 20 age- and sex-matched typically developing children;
(ii) a discovery cohort of 99 healthy adults stratified by
LIMK1 haplotype; (iii) a replication cohort of 32 healthy
adults also stratified by LIMK1 haplotype; and (iv) 339
healthy adolescent children stratified by LIMK1 haplotype.
For between-group analyses, differences in intraparietal
sulcus resting-state functional connectivity were calculated
comparing children with Williams syndrome to matched
typically developing children and comparing LIMK1 haplotype
groups in each of the three general population cohorts
separately. Consistent with the visuospatial construction
impairment and hypersocial personality that typify Williams
syndrome, the Williams syndrome cohort exhibited opposite
patterns of intraparietal sulcus functional connectivity
with visual processing regions and social processing
regions: decreased circuit function in the former and
increased circuit function in the latter. All three general
population groups also showed LIMK1 haplotype-related
differences in intraparietal sulcus functional connectivity
localized to the fusiform gyrus, a visual processing region
also identified in the Williams syndrome-typically
developing comparison. These results suggest a neurogenetic
mechanism, in part involving LIMK1, that may bias neural
circuit function in both the general population and
individuals with Williams syndrome.},
Doi = {10.1093/brain/awz323},
Key = {fds350914}
}
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