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| Publications of Karen Sugden :chronological alphabetical combined listing:
%% Journal Articles
@article{fds363996,
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},
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 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 = {fds363996}
}
@article{fds339458,
Author = {Rasmussen, LJH and Moffitt, TE and Eugen-Olsen, J and Belsky, DW and Danese, A and Harrington, H and Houts, RM and Poulton, R and Sugden, K and Williams, B and Caspi, A},
Title = {Cumulative childhood risk is associated with a new measure
of chronic inflammation in adulthood.},
Journal = {Journal of Child Psychology and Psychiatry, and Allied
Disciplines},
Volume = {60},
Number = {2},
Pages = {199-208},
Year = {2019},
Month = {February},
url = {http://dx.doi.org/10.1111/jcpp.12928},
Abstract = {Childhood risk factors are associated with elevated
inflammatory biomarkers in adulthood, but it is unknown
whether these risk factors are associated with increased
adult levels of the chronic inflammation marker soluble
urokinase plasminogen activator receptor (suPAR). We aimed
to test the hypothesis that childhood exposure to risk
factors for adult disease is associated with elevated suPAR
in adulthood and to compare suPAR with the oft-reported
inflammatory biomarker C-reactive protein (CRP). Prospective
study of a population-representative 1972-1973 birth cohort;
the Dunedin Multidisciplinary Health and Development Study
observed participants to age 38 years. Main childhood
predictors were poor health, socioeconomic disadvantage,
adverse childhood experiences (ACEs), low IQ, and poor
self-control. Main adult outcomes were adulthood
inflammation measured as suPAR and high-sensitivity CRP
(hsCRP). Participants with available plasma samples at age
38 were included (N = 837, 50.5% male). suPAR (mean
2.40 ng/ml; SD 0.91) was positively correlated with hsCRP
(r 0.15, p < .001). After controlling for sex, body mass
index (BMI), and smoking, children who experienced more
ACEs, lower IQ, or had poorer self-control showed elevated
adult suPAR. When the five childhood risks were aggregated
into a Cumulative Childhood Risk index, and controlling for
sex, BMI, and smoking, Cumulative Childhood Risk was
associated with higher suPAR (b 0.10; SE 0.03; p = .002).
Cumulative Childhood Risk predicted elevated suPAR, after
controlling for hsCRP (b 0.18; SE 0.03; p < .001).
Exposure to more childhood risk factors was associated with
higher suPAR levels, independent of CRP. suPAR is a useful
addition to studies connecting childhood risk to adult
inflammatory burden.},
Doi = {10.1111/jcpp.12928},
Key = {fds339458}
}
@article{fds340987,
Author = {Hannon, E and Knox, O and Sugden, K and Burrage, J and Wong, CCY and Belsky, DW and Corcoran, DL and Arseneault, L and Moffitt, TE and Caspi,
A and Mill, J},
Title = {Characterizing genetic and environmental influences on
variable DNA methylation using monozygotic and dizygotic
twins.},
Journal = {Plos Genetics},
Volume = {14},
Number = {8},
Pages = {e1007544},
Year = {2018},
Month = {August},
url = {http://dx.doi.org/10.1371/journal.pgen.1007544},
Abstract = {Variation in DNA methylation is being increasingly
associated with health and disease outcomes. Although DNA
methylation is hypothesized to be a mechanism by which both
genetic and non-genetic factors can influence the regulation
of gene expression, little is known about the extent to
which DNA methylation at specific sites is influenced by
heritable as well as environmental factors. We quantified
DNA methylation in whole blood at age 18 in a birth cohort
of 1,464 individuals comprising 426 monozygotic (MZ) and 306
same-sex dizygotic (DZ) twin pairs. Site-specific levels of
DNA methylation were more strongly correlated across the
genome between MZ than DZ twins. Structural equation models
revealed that although the average contribution of additive
genetic influences on DNA methylation across the genome was
relatively low, it was notably elevated at the highly
variable sites characterized by intermediate levels of DNAm
that are most relevant for epigenetic epidemiology. Sites at
which variable DNA methylation was most influenced by
genetic factors were significantly enriched for DNA
methylation quantitative trait loci (mQTL) effects, and
overlapped with sites where inter-individual variation
correlates across tissues. Finally, we show that DNA
methylation at sites robustly associated with environmental
exposures such as tobacco smoking and obesity is also
influenced by additive genetic effects, highlighting the
need to control for genetic background in analyses of
exposure-associated DNA methylation differences. Estimates
of the contribution of genetic and environmental influences
to DNA methylation at all sites profiled in this study are
available as a resource for the research community
(http://www.epigenomicslab.com/online-data-resources).},
Doi = {10.1371/journal.pgen.1007544},
Key = {fds340987}
}
@article{fds339457,
Author = {Belsky, DW and Moffitt, TE and Cohen, AA and Corcoran, DL and Levine,
ME and Prinz, JA and Schaefer, J and Sugden, K and Williams, B and Poulton,
R and Caspi, A},
Title = {Eleven Telomere, Epigenetic Clock, and Biomarker-Composite
Quantifications of Biological Aging: Do They Measure the
Same Thing?},
Journal = {American Journal of Epidemiology},
Volume = {187},
Number = {6},
Pages = {1220-1230},
Year = {2018},
Month = {June},
url = {http://dx.doi.org/10.1093/aje/kwx346},
Abstract = {The geroscience hypothesis posits that therapies to slow
biological processes of aging can prevent disease and extend
healthy years of life. To test such "geroprotective"
therapies in humans, outcome measures are needed that can
assess extension of disease-free life span. This need has
spurred development of different methods to quantify
biological aging. But different methods have not been
systematically compared in the same humans. We implemented 7
methods to quantify biological aging using repeated-measures
physiological and genomic data in 964 middle-aged humans in
the Dunedin Study (New Zealand; persons born 1972-1973). We
studied 11 measures in total: telomere-length and erosion, 3
epigenetic-clocks and their ticking rates, and 3
biomarker-composites. Contrary to expectation, we found low
agreement between different measures of biological aging. We
next compared associations between biological aging measures
and outcomes that geroprotective therapies seek to modify:
physical functioning, cognitive decline, and subjective
signs of aging, including aged facial appearance. The
71-cytosine-phosphate-guanine epigenetic clock and biomarker
composites were consistently related to these aging-related
outcomes. However, effect sizes were modest. Results
suggested that various proposed approaches to quantifying
biological aging may not measure the same aspects of the
aging process. Further systematic evaluation and refinement
of measures of biological aging is needed to furnish
outcomes for geroprotector trials.},
Doi = {10.1093/aje/kwx346},
Key = {fds339457}
}
@article{fds339456,
Author = {Marzi, SJ and Sugden, K and Arseneault, L and Belsky, DW and Burrage, J and Corcoran, DL and Danese, A and Fisher, HL and Hannon, E and Moffitt, TE and Odgers, CL and Pariante, C and Poulton, R and Williams, BS and Wong,
CCY and Mill, J and Caspi, A},
Title = {Analysis of DNA Methylation in Young People: Limited
Evidence for an Association Between Victimization Stress and
Epigenetic Variation in Blood.},
Journal = {The American Journal of Psychiatry},
Volume = {175},
Number = {6},
Pages = {517-529},
Year = {2018},
Month = {June},
url = {http://dx.doi.org/10.1176/appi.ajp.2017.17060693},
Abstract = {<h4>Objective</h4>DNA methylation has been proposed as an
epigenetic mechanism by which early-life experiences become
"embedded" in the genome and alter transcriptional processes
to compromise health. The authors sought to investigate
whether early-life victimization stress is associated with
genome-wide DNA methylation.<h4>Method</h4>The authors
tested the hypothesis that victimization is associated with
DNA methylation in the Environmental Risk (E-Risk)
Longitudinal Study, a nationally representative 1994-1995
birth cohort of 2,232 twins born in England and Wales and
assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms
of victimization were ascertained in childhood and
adolescence (including physical, sexual, and emotional
abuse; neglect; exposure to intimate-partner violence;
bullying; cyber-victimization; and crime).<h4>Results</h4>Epigenome-wide
analyses of polyvictimization across childhood and
adolescence revealed few significant associations with DNA
methylation in peripheral blood at age 18, but these
analyses were confounded by tobacco smoking and/or did not
survive co-twin control tests. Secondary analyses of
specific forms of victimization revealed sparse associations
with DNA methylation that did not replicate across different
operationalizations of the same putative victimization
experience. Hypothesis-driven analyses of six candidate
genes in the stress response (NR3C1, FKBP5, BDNF, AVP,
CRHR1, SLC6A4) did not reveal predicted associations with
DNA methylation in probes annotated to these
genes.<h4>Conclusions</h4>Findings from this epidemiological
analysis of the epigenetic effects of early-life stress do
not support the hypothesis of robust changes in DNA
methylation in victimized young people. We need to come to
terms with the possibility that epigenetic epidemiology is
not yet well matched to experimental, nonhuman models in
uncovering the biological embedding of stress.},
Doi = {10.1176/appi.ajp.2017.17060693},
Key = {fds339456}
}
@article{fds339459,
Author = {Wertz, J and Caspi, A and Belsky, DW and Beckley, AL and Arseneault, L and Barnes, JC and Corcoran, DL and Hogan, S and Houts, RM and Morgan, N and Odgers, CL and Prinz, JA and Sugden, K and Williams, BS and Poulton, R and Moffitt, TE},
Title = {Genetics and Crime: Integrating New Genomic Discoveries Into
Psychological Research About Antisocial Behavior.},
Journal = {Psychological Science},
Volume = {29},
Number = {5},
Pages = {791-803},
Year = {2018},
Month = {May},
url = {http://dx.doi.org/10.1177/0956797617744542},
Abstract = {Drawing on psychological and sociological theories of crime
causation, we tested the hypothesis that genetic risk for
low educational attainment (assessed via a genome-wide
polygenic score) is associated with criminal offending. We
further tested hypotheses of how polygenic risk relates to
the development of antisocial behavior from childhood
through adulthood. Across the Dunedin and Environmental Risk
(E-Risk) birth cohorts of individuals growing up 20 years
and 20,000 kilometers apart, education polygenic scores
predicted risk of a criminal record with modest effects.
Polygenic risk manifested during primary schooling in lower
cognitive abilities, lower self-control, academic
difficulties, and truancy, and it was associated with a
life-course-persistent pattern of antisocial behavior that
onsets in childhood and persists into adulthood. Crime is
central in the nature-nurture debate, and findings reported
here demonstrate how molecular-genetic discoveries can be
incorporated into established theories of antisocial
behavior. They also suggest that improving school
experiences might prevent genetic influences on crime from
unfolding.},
Doi = {10.1177/0956797617744542},
Key = {fds339459}
}
@article{fds339460,
Author = {Baldwin, JR and Arseneault, L and Caspi, A and Fisher, HL and Moffitt,
TE and Odgers, CL and Pariante, C and Ambler, A and Dove, R and Kepa, A and Matthews, T and Menard, A and Sugden, K and Williams, B and Danese,
A},
Title = {Childhood victimization and inflammation in young adulthood:
A genetically sensitive cohort study.},
Journal = {Brain, Behavior, and Immunity},
Volume = {67},
Pages = {211-217},
Year = {2018},
Month = {January},
url = {http://dx.doi.org/10.1016/j.bbi.2017.08.025},
Abstract = {<h4>Objective</h4>Childhood victimization is an important
risk factor for later immune-related disorders. Previous
evidence has demonstrated that childhood victimization is
associated with elevated levels of inflammation biomarkers
measured decades after exposure. However, it is unclear
whether this association is (1) already detectable in young
people, (2) different in males and females, and (3)
confounded by genetic liability to inflammation. Here we
sought to address these questions.<h4>Method</h4>Participants
were 2232 children followed from birth to age 18years as
part of the Environmental Risk (E-Risk) Longitudinal Twin
Study. Childhood victimization was measured prospectively
from birth to age 12years. Inflammation was measured through
C-reactive protein (CRP) levels in dried blood spots at age
18years. Latent genetic liability for high inflammation
levels was assessed through a twin-based
method.<h4>Results</h4>Greater exposure to childhood
victimization was associated with higher CRP levels at age
18 (serum-equivalent means were 0.65 in non-victimized Study
members, 0.74 in those exposed to one victimization type,
and 0.81 in those exposed to poly-victimization; p=0.018).
However, this association was driven by a significant
association in females (serum-equivalent means were 0.75 in
non-victimized females, 0.87 in those exposed to one type of
victimization, and 1.19 in those exposed to
poly-victimization; p=0.010), while no significant
association was observed in males (p=0.19). Victimized
females showed elevated CRP levels independent of latent
genetic influence, as well as childhood socioeconomic
status, and waist-hip ratio and body temperature at the time
of CRP assessment.<h4>Conclusion</h4>Childhood victimization
is associated with elevated CRP levels in young women,
independent of latent genetic influences and other key risk
factors. These results strengthen causal inference about the
effects of childhood victimization on inflammation levels in
females by accounting for potential genetic
confounding.},
Doi = {10.1016/j.bbi.2017.08.025},
Key = {fds339460}
}
@article{fds339461,
Author = {Reuben, A and Caspi, A and Belsky, DW and Broadbent, J and Harrington,
H and Sugden, K and Houts, RM and Ramrakha, S and Poulton, R and Moffitt,
TE},
Title = {Association of Childhood Blood Lead Levels With Cognitive
Function and Socioeconomic Status at Age 38 Years and With
IQ Change and Socioeconomic Mobility Between Childhood and
Adulthood.},
Journal = {Jama},
Volume = {317},
Number = {12},
Pages = {1244-1251},
Year = {2017},
Month = {March},
url = {http://dx.doi.org/10.1001/jama.2017.1712},
Abstract = {<h4>Importance</h4>Many children in the United States and
around the world are exposed to lead, a developmental
neurotoxin. The long-term cognitive and socioeconomic
consequences of lead exposure are uncertain.<h4>Objective</h4>To
test the hypothesis that childhood lead exposure is
associated with cognitive function and socioeconomic status
in adulthood and with changes in IQ and socioeconomic
mobility between childhood and midlife.<h4>Design, setting,
and participants</h4>A prospective cohort study based on a
population-representative 1972-1973 birth cohort from New
Zealand; the Dunedin Multidisciplinary Health and
Development Study observed participants to age 38 years
(until December 2012).<h4>Exposures</h4>Childhood lead
exposure ascertained as blood lead levels measured at age 11
years. High blood lead levels were observed among children
from all socioeconomic status levels in this cohort.<h4>Main
outcomes and measures</h4>The IQ (primary outcome) and
indexes of Verbal Comprehension, Perceptual Reasoning,
Working Memory, and Processing Speed (secondary outcomes)
were assessed at age 38 years using the Wechsler Adult
Intelligence Scale-IV (WAIS-IV; IQ range, 40-160).
Socioeconomic status (primary outcome) was assessed at age
38 years using the New Zealand Socioeconomic Index-2006
(NZSEI-06; range, 10 [lowest]-90 [highest]).<h4>Results</h4>Of
1037 original participants, 1007 were alive at age 38 years,
of whom 565 (56%) had been lead tested at age 11 years (54%
male; 93% white). Mean (SD) blood lead level at age 11 years
was 10.99 (4.63) µg/dL. Among blood-tested participants
included at age 38 years, mean WAIS-IV score was 101.16
(14.82) and mean NZSEI-06 score was 49.75 (17.12). After
adjusting for maternal IQ, childhood IQ, and childhood
socioeconomic status, each 5-µg/dL higher level of blood
lead in childhood was associated with a 1.61-point lower
score (95% CI, -2.48 to -0.74) in adult IQ, a 2.07-point
lower score (95% CI, -3.14 to -1.01) in perceptual
reasoning, and a 1.26-point lower score (95% CI, -2.38 to
-0.14) in working memory. Associations of childhood blood
lead level with deficits in verbal comprehension and
processing speed were not statistically significant. After
adjusting for confounders, each 5-µg/dL higher level of
blood lead in childhood was associated with a 1.79-unit
lower score (95% CI, -3.17 to -0.40) in socioeconomic
status. An association between greater blood lead levels and
a decline in IQ and socioeconomic status from childhood to
adulthood was observed with 40% of the association with
downward mobility mediated by cognitive decline from
childhood.<h4>Conclusions and relevance</h4>In this cohort
born in New Zealand in 1972-1973, childhood lead exposure
was associated with lower cognitive function and
socioeconomic status at age 38 years and with declines in IQ
and with downward social mobility. Childhood lead exposure
may have long-term ramifications.},
Doi = {10.1001/jama.2017.1712},
Key = {fds339461}
}
@article{fds339462,
Author = {Schaefer, JD and Caspi, A and Belsky, DW and Harrington, H and Houts, R and Israel, S and Levine, ME and Sugden, K and Williams, B and Poulton, R and Moffitt, TE},
Title = {Early-Life Intelligence Predicts Midlife Biological
Age.},
Journal = {The Journals of Gerontology. Series B, Psychological
Sciences and Social Sciences},
Volume = {71},
Number = {6},
Pages = {968-977},
Year = {2016},
Month = {November},
url = {http://dx.doi.org/10.1093/geronb/gbv035},
Abstract = {<h4>Objectives</h4>Early-life intelligence has been shown to
predict multiple causes of death in populations around the
world. This finding suggests that intelligence might
influence mortality through its effects on a general process
of physiological deterioration (i.e., individual variation
in "biological age"). We examined whether intelligence could
predict measures of aging at midlife before the onset of
most age-related disease.<h4>Methods</h4>We tested whether
intelligence assessed in early childhood, middle childhood,
and midlife predicted midlife biological age in members of
the Dunedin Study, a population-representative birth
cohort.<h4>Results</h4>Lower intelligence predicted more
advanced biological age at midlife as captured by perceived
facial age, a 10-biomarker algorithm based on data from the
National Health and Nutrition Examination Survey (NHANES),
and Framingham heart age (r = 0.1-0.2). Correlations between
intelligence and telomere length were less consistent. The
associations between intelligence and biological age were
not explained by differences in childhood health or parental
socioeconomic status, and intelligence remained a
significant predictor of biological age even when
intelligence was assessed before Study members began their
formal schooling.<h4>Discussion</h4>These results suggest
that accelerated aging may serve as one of the factors
linking low early-life intelligence to increased rates of
morbidity and mortality.},
Doi = {10.1093/geronb/gbv035},
Key = {fds339462}
}
@article{fds339463,
Author = {Belsky, DW and Moffitt, TE and Corcoran, DL and Domingue, B and Harrington, H and Hogan, S and Houts, R and Ramrakha, S and Sugden, K and Williams, BS and Poulton, R and Caspi, A},
Title = {The Genetics of Success: How Single-Nucleotide Polymorphisms
Associated With Educational Attainment Relate to Life-Course
Development.},
Journal = {Psychological Science},
Volume = {27},
Number = {7},
Pages = {957-972},
Year = {2016},
Month = {July},
url = {http://dx.doi.org/10.1177/0956797616643070},
Abstract = {A previous genome-wide association study (GWAS) of more than
100,000 individuals identified molecular-genetic predictors
of educational attainment. We undertook in-depth life-course
investigation of the polygenic score derived from this GWAS
using the four-decade Dunedin Study (N = 918). There were
five main findings. First, polygenic scores predicted adult
economic outcomes even after accounting for educational
attainments. Second, genes and environments were correlated:
Children with higher polygenic scores were born into
better-off homes. Third, children's polygenic scores
predicted their adult outcomes even when analyses accounted
for their social-class origins; social-mobility analysis
showed that children with higher polygenic scores were more
upwardly mobile than children with lower scores. Fourth,
polygenic scores predicted behavior across the life course,
from early acquisition of speech and reading skills through
geographic mobility and mate choice and on to financial
planning for retirement. Fifth, polygenic-score associations
were mediated by psychological characteristics, including
intelligence, self-control, and interpersonal skill. Effect
sizes were small. Factors connecting DNA sequence with life
outcomes may provide targets for interventions to promote
population-wide positive development.},
Doi = {10.1177/0956797616643070},
Key = {fds339463}
}
@article{fds339464,
Author = {Sugden, K and Moffitt, TE and Pinto, L and Poulton, R and Williams, BS and Caspi, A},
Title = {Is Toxoplasma Gondii Infection Related to Brain and Behavior
Impairments in Humans? Evidence from a Population-Representative
Birth Cohort},
Journal = {Plos One},
Volume = {11},
Number = {2},
Year = {2016},
Month = {February},
url = {http://dx.doi.org/10.1371/journal.pone.0148435},
Doi = {10.1371/journal.pone.0148435},
Key = {fds339464}
}
@article{fds339465,
Author = {Sugden, K and Moffitt, TE and Pinto, L and Poulton, R and Williams, BS and Caspi, A},
Title = {Is Toxoplasma Gondii Infection Related to Brain and Behavior
Impairments in Humans? Evidence from a Population-Representative
Birth Cohort.},
Journal = {Plos One},
Volume = {11},
Number = {2},
Pages = {e0148435},
Year = {2016},
Month = {January},
url = {http://dx.doi.org/10.1371/journal.pone.0148435},
Abstract = {<h4>Background</h4>Toxoplasma gondii (T. gondii) is a
protozoan parasite present in around a third of the human
population. Infected individuals are commonly asymptomatic,
though recent reports have suggested that infection might
influence aspects of the host's behavior. In particular,
Toxoplasma infection has been linked to schizophrenia,
suicide attempt, differences in aspects of personality and
poorer neurocognitive performance. However, these studies
are often conducted in clinical samples or convenience
samples.<h4>Methods/results</h4>In a population-representative
birth-cohort of individuals tested for presence of
antibodies to T. gondii (N = 837) we investigated the
association between infection and four facets of human
behavior: neuropsychiatric disorder (schizophrenia and major
depression), poor impulse control (suicidal behavior and
criminality), personality, and neurocognitive performance.
Suicide attempt was marginally more frequent among
individuals with T. gondii seropositivity (p = .06).
Seropositive individuals also performed worse on one out of
14 measures of neuropsychological function.<h4>Conclusion</h4>On
the whole, there was little evidence that T. gondii was
related to increased risk of psychiatric disorder, poor
impulse control, personality aberrations or neurocognitive
impairment.},
Doi = {10.1371/journal.pone.0148435},
Key = {fds339465}
}
@article{fds339466,
Author = {Moffitt, TE and Houts, R and Asherson, P and Belsky, DW and Corcoran,
DL and Hammerle, M and Harrington, H and Hogan, S and Meier, MH and Polanczyk, GV and Poulton, R and Ramrakha, S and Sugden, K and Williams,
B and Rohde, LA and Caspi, A},
Title = {Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder?
Evidence From a Four-Decade Longitudinal Cohort
Study.},
Journal = {The American Journal of Psychiatry},
Volume = {172},
Number = {10},
Pages = {967-977},
Year = {2015},
Month = {October},
url = {http://dx.doi.org/10.1176/appi.ajp.2015.14101266},
Abstract = {<h4>Objective</h4>Despite a prevailing assumption that adult
ADHD is a childhood-onset neurodevelopmental disorder, no
prospective longitudinal study has described the childhoods
of the adult ADHD population. The authors report follow-back
analyses of ADHD cases diagnosed in adulthood, alongside
follow-forward analyses of ADHD cases diagnosed in
childhood, in one cohort.<h4>Method</h4>Participants
belonged to a representative birth cohort of 1,037
individuals born in Dunedin, New Zealand, in 1972 and 1973
and followed to age 38, with 95% retention. Symptoms of
ADHD, associated clinical features, comorbid disorders,
neuropsychological deficits, genome-wide association
study-derived polygenic risk, and life impairment indicators
were assessed. Data sources were participants, parents,
teachers, informants, neuropsychological test results, and
administrative records. Adult ADHD diagnoses used DSM-5
criteria, apart from onset age and cross-setting
corroboration, which were study outcome measures.<h4>Results</h4>As
expected, childhood ADHD had a prevalence of 6%
(predominantly male) and was associated with childhood
comorbid disorders, neurocognitive deficits, polygenic risk,
and residual adult life impairment. Also as expected, adult
ADHD had a prevalence of 3% (gender balanced) and was
associated with adult substance dependence, adult life
impairment, and treatment contact. Unexpectedly, the
childhood ADHD and adult ADHD groups comprised virtually
nonoverlapping sets; 90% of adult ADHD cases lacked a
history of childhood ADHD. Also unexpectedly, the adult ADHD
group did not show tested neuropsychological deficits in
childhood or adulthood, nor did they show polygenic risk for
childhood ADHD.<h4>Conclusions</h4>The findings raise the
possibility that adults presenting with the ADHD symptom
picture may not have a childhood-onset neurodevelopmental
disorder. If this finding is replicated, then the disorder's
place in the classification system must be reconsidered, and
research must investigate the etiology of adult
ADHD.},
Doi = {10.1176/appi.ajp.2015.14101266},
Key = {fds339466}
}
@article{fds339467,
Author = {Belsky, DW and Caspi, A and Houts, R and Cohen, HJ and Corcoran, DL and Danese, A and Harrington, H and Israel, S and Levine, ME and Schaefer,
JD and Sugden, K and Williams, B and Yashin, AI and Poulton, R and Moffitt,
TE},
Title = {Quantification of biological aging in young
adults.},
Journal = {Proc Natl Acad Sci U S A},
Volume = {112},
Number = {30},
Pages = {E4104-E4110},
Year = {2015},
Month = {July},
url = {http://dx.doi.org/10.1073/pnas.1506264112},
Abstract = {Antiaging therapies show promise in model organism research.
Translation to humans is needed to address the challenges of
an aging global population. Interventions to slow human
aging will need to be applied to still-young individuals.
However, most human aging research examines older adults,
many with chronic disease. As a result, little is known
about aging in young humans. We studied aging in 954 young
humans, the Dunedin Study birth cohort, tracking multiple
biomarkers across three time points spanning their third and
fourth decades of life. We developed and validated two
methods by which aging can be measured in young adults, one
cross-sectional and one longitudinal. Our longitudinal
measure allows quantification of the pace of coordinated
physiological deterioration across multiple organ systems
(e.g., pulmonary, periodontal, cardiovascular, renal,
hepatic, and immune function). We applied these methods to
assess biological aging in young humans who had not yet
developed age-related diseases. Young individuals of the
same chronological age varied in their "biological aging"
(declining integrity of multiple organ systems). Already,
before midlife, individuals who were aging more rapidly were
less physically able, showed cognitive decline and brain
aging, self-reported worse health, and looked older.
Measured biological aging in young adults can be used to
identify causes of aging and evaluate rejuvenation
therapies.},
Doi = {10.1073/pnas.1506264112},
Key = {fds339467}
}
@article{fds339468,
Author = {Sugden, K and Danese, A and Shalev, I and Williams, BS and Caspi,
A},
Title = {Blood Substrate Collection and Handling Procedures under
Pseudo-Field Conditions: Evaluation of Suitability for
Inflammatory Biomarker Measurement.},
Journal = {Biodemography and Social Biology},
Volume = {61},
Number = {3},
Pages = {273-284},
Year = {2015},
Month = {January},
url = {http://dx.doi.org/10.1080/19485565.2015.1062717},
Abstract = {Routine incorporation of blood-based biomarker measurements
in population studies has been hampered by challenges in
obtaining samples suitable for biomarker assessment outside
of laboratory settings. Here, we assessed the suitability of
venous blood left unprocessed for 4, 24, or 48 hours
post-collection at either room temperature or 4°C for
quantification of two biomarkers, Interleukin-6 (IL-6) and
C-reactive protein (CRP). Blood samples were collected in
both K2EDTA tubes and a dedicated plasma-preservation tube,
P100. Dried blood spot (DBS) samples from the same subjects
were also collected in order to compare delayed-processing
plasma performance against a popular alternative collection
method. We found that K2EDTA mean plasma concentrations of
both IL-6 and CRP were not significantly different from
concentrations in plasma processed immediately; this was
observed for tubes stored up to 48 hours pre-processing at
either temperature. Concentrations of IL-6 measured in P100
tubes showed significant time-dependent increases when
stored at room temperature; otherwise, levels of IL-6 and
CRP were similar to those found in samples processed
immediately. Levels of CRP in DBS were correlated with
plasma CRP levels, even when pre-processed blood was stored
for up to 48 hours. These data indicate that plasma is
suitable for IL-6 and CRP estimation under data collection
conditions that involve processing delays.},
Doi = {10.1080/19485565.2015.1062717},
Key = {fds339468}
}
@article{fds339471,
Author = {Shalev, I and Caspi, A and Ambler, A and Belsky, DW and Chapple, S and Cohen, HJ and Israel, S and Poulton, R and Ramrakha, S and Rivera, CD and Sugden, K and Williams, B and Wolke, D and Moffitt,
TE},
Title = {Perinatal complications and aging indicators by
midlife.},
Journal = {Pediatrics},
Volume = {134},
Number = {5},
Pages = {e1315-e1323},
Year = {2014},
Month = {November},
url = {http://dx.doi.org/10.1542/peds.2014-1669},
Abstract = {BACKGROUND: Perinatal complications predict increased risk
for morbidity and early mortality. Evidence of perinatal
programming of adult mortality raises the question of what
mechanisms embed this long-term effect. We tested a
hypothesis related to the theory of developmental origins of
health and disease: that perinatal complications assessed at
birth predict indicators of accelerated aging by midlife.
METHODS: Perinatal complications, including both maternal
and neonatal complications, were assessed in the Dunedin
Multidisciplinary Health and Development Study cohort (N =
1037), a 38-year, prospective longitudinal study of a
representative birth cohort. Two aging indicators were
assessed at age 38 years, objectively by leukocyte telomere
length (TL) and subjectively by perceived facial age.
RESULTS: Perinatal complications predicted both leukocyte TL
(β = -0.101; 95% confidence interval, -0.169 to -0.033; P =
.004) and perceived age (β = 0.097; 95% confidence
interval, 0.029 to 0.165; P = .005) by midlife. We repeated
analyses with controls for measures of family history and
social risk that could predispose to perinatal complications
and accelerated aging, and for measures of poor health taken
in between birth and the age-38 follow-up. These covariates
attenuated, but did not fully explain the associations
observed between perinatal complications and aging
indicators. CONCLUSIONS: Our findings provide support for
early-life developmental programming by linking newborns'
perinatal complications to accelerated aging at midlife. We
observed indications of accelerated aging "inside," as
measured by leukocyte TL, an indicator of cellular aging,
and "outside," as measured by perceived age, an indicator of
declining tissue integrity. A better understanding of
mechanisms underlying perinatal programming of adult aging
is needed.},
Doi = {10.1542/peds.2014-1669},
Key = {fds339471}
}
@article{fds339470,
Author = {Shalev, I and Moffitt, TE and Braithwaite, AW and Danese, A and Fleming,
NI and Goldman-Mellor, S and Harrington, HL and Houts, RM and Israel, S and Poulton, R and Robertson, SP and Sugden, K and Williams, B and Caspi,
A},
Title = {Internalizing disorders and leukocyte telomere erosion: a
prospective study of depression, generalized anxiety
disorder and post-traumatic stress disorder.},
Journal = {Molecular Psychiatry},
Volume = {19},
Number = {11},
Pages = {1163-1170},
Year = {2014},
Month = {November},
url = {http://dx.doi.org/10.1038/mp.2013.183},
Abstract = {There is evidence that persistent psychiatric disorders lead
to age-related disease and premature mortality. Telomere
length has emerged as a promising biomarker in studies that
test the hypothesis that internalizing psychiatric disorders
are associated with accumulating cellular damage. We tested
the association between the persistence of internalizing
disorders (depression, generalized anxiety disorder and
post-traumatic stress disorder) and leukocyte telomere
length (LTL) in the prospective longitudinal Dunedin Study
(n=1037). Analyses showed that the persistence of
internalizing disorders across repeated assessments from
ages 11 to 38 years predicted shorter LTL at age 38 years in
a dose-response manner, specifically in men (β=-0.137, 95%
confidence interval (CI): -0.232, -0.042, P=0.005). This
association was not accounted for by alternative explanatory
factors, including childhood maltreatment, tobacco smoking,
substance dependence, psychiatric medication use, poor
physical health or low socioeconomic status. Additional
analyses using DNA from blood collected at two time points
(ages 26 and 38 years) showed that LTL erosion was
accelerated among men who were diagnosed with internalizing
disorder in the interim (β=-0.111, 95% CI: -0.184, -0.037,
P=0.003). No significant associations were found among women
in any analysis, highlighting potential sex differences in
internalizing-related telomere biology. These findings point
to a potential mechanism linking internalizing disorders to
accelerated biological aging in the first half of the life
course, particularly in men. Because internalizing disorders
are treatable, the findings suggest the hypothesis that
treating psychiatric disorders in the first half of the life
course may reduce the population burden of age-related
disease and extend health expectancy.},
Doi = {10.1038/mp.2013.183},
Key = {fds339470}
}
@article{fds339472,
Author = {Belsky, DW and Shalev, I and Sears, MR and Hancox, RJ and Lee
Harrington, H and Houts, R and Moffitt, TE and Sugden, K and Williams,
B and Poulton, R and Caspi, A},
Title = {Is chronic asthma associated with shorter leukocyte telomere
length at midlife?},
Journal = {American Journal of Respiratory and Critical Care
Medicine},
Volume = {190},
Number = {4},
Pages = {384-391},
Year = {2014},
Month = {August},
url = {http://dx.doi.org/10.1164/rccm.201402-0370OC},
Abstract = {RATIONALE: Asthma is prospectively associated with
age-related chronic diseases and mortality, suggesting the
hypothesis that asthma may relate to a general, multisystem
phenotype of accelerated aging. OBJECTIVES: To test whether
chronic asthma is associated with a proposed biomarker of
accelerated aging, leukocyte telomere length. METHODS:
Asthma was ascertained prospectively in the Dunedin
Multidisciplinary Health and Development Study cohort (n =
1,037) at nine in-person assessments spanning ages 9-38
years. Leukocyte telomere length was measured at ages 26 and
38 years. Asthma was classified as life-course-persistent,
childhood-onset not meeting criteria for persistence, and
adolescent/adult-onset. We tested associations between
asthma and leukocyte telomere length using regression
models. We tested for confounding of asthma-leukocyte
telomere length associations using covariate adjustment. We
tested serum C-reactive protein and white blood cell counts
as potential mediators of asthma-leukocyte telomere length
associations. MEASUREMENTS AND MAIN RESULTS: Study members
with life-course-persistent asthma had shorter leukocyte
telomere length as compared with sex- and age-matched peers
with no reported asthma. In contrast, leukocyte telomere
length in study members with childhood-onset and
adolescent/adult-onset asthma was not different from
leukocyte telomere length in peers with no reported asthma.
Adjustment for life histories of obesity and smoking did not
change results. Study members with life-course-persistent
asthma had elevated blood eosinophil counts. Blood
eosinophil count mediated 29% of the life-course-persistent
asthma-leukocyte telomere length association. CONCLUSIONS:
Life-course-persistent asthma is related to a proposed
biomarker of accelerated aging, possibly via systemic
eosinophilic inflammation. Life histories of asthma can
inform studies of aging.},
Doi = {10.1164/rccm.201402-0370OC},
Key = {fds339472}
}
@article{fds339475,
Author = {Shalev, I and Moffitt, TE and Sugden, K and Williams, B and Houts, RM and Danese, A and Mill, J and Arseneault, L and Caspi,
A},
Title = {Exposure to violence during childhood is associated with
telomere erosion from 5 to 10 years of age: a longitudinal
study.},
Journal = {Molecular Psychiatry},
Volume = {18},
Number = {5},
Pages = {576-581},
Year = {2013},
Month = {May},
url = {http://dx.doi.org/10.1038/mp.2012.32},
Abstract = {There is increasing interest in discovering mechanisms that
mediate the effects of childhood stress on late-life disease
morbidity and mortality. Previous studies have suggested one
potential mechanism linking stress to cellular aging,
disease and mortality in humans: telomere erosion. We
examined telomere erosion in relation to children's exposure
to violence, a salient early-life stressor, which has known
long-term consequences for well-being and is a major
public-health and social-welfare problem. In the first
prospective-longitudinal study with repeated telomere
measurements in children while they experienced stress, we
tested the hypothesis that childhood violence exposure would
accelerate telomere erosion from age 5 to age 10 years.
Violence was assessed as exposure to maternal domestic
violence, frequent bullying victimization and physical
maltreatment by an adult. Participants were 236 children
(49% females; 42% with one or more violence exposures)
recruited from the Environmental-Risk Longitudinal Twin
Study, a nationally representative 1994-1995 birth cohort.
Each child's mean relative telomere length was measured
simultaneously in baseline and follow-up DNA samples, using
the quantitative PCR method for T/S ratio (the ratio of
telomere repeat copy numbers to single-copy gene numbers).
Compared with their counterparts, the children who
experienced two or more kinds of violence exposure showed
significantly more telomere erosion between age-5 baseline
and age-10 follow-up measurements, even after adjusting for
sex, socioeconomic status and body mass index (B=-0.052,
s.e.=0.021, P=0.015). This finding provides support for a
mechanism linking cumulative childhood stress to telomere
maintenance, observed already at a young age, with potential
impact for life-long health.},
Doi = {10.1038/mp.2012.32},
Key = {fds339475}
}
@article{fds339476,
Author = {Belsky, DW and Moffitt, TE and Baker, TB and Biddle, AK and Evans, JP and Harrington, H and Houts, R and Meier, M and Sugden, K and Williams, B and Poulton, R and Caspi, A},
Title = {Polygenic risk and the developmental progression to heavy,
persistent smoking and nicotine dependence: evidence from a
4-decade longitudinal study.},
Journal = {Jama Psychiatry},
Volume = {70},
Number = {5},
Pages = {534-542},
Year = {2013},
Month = {May},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2013.736},
Abstract = {<h4>Importance</h4>Genome-wide hypothesis-free discovery
methods have identified loci that are associated with heavy
smoking in adulthood. Research is needed to understand
developmental processes that link newly discovered genetic
risks with adult heavy smoking.<h4>Objective</h4>To test how
genetic risks discovered in genome-wide association studies
of adult smoking influence the developmental progression of
smoking behavior from initiation through conversion to daily
smoking, progression to heavy smoking, nicotine dependence,
and struggles with cessation.<h4>Design</h4>A 38-year,
prospective, longitudinal study of a representative birth
cohort.<h4>Setting</h4>The Dunedin Multidisciplinary Health
and Development Study of New Zealand.<h4>Participants</h4>The
study included 1037 male and female participants.<h4>Exposure</h4>We
assessed genetic risk with a multilocus genetic risk score.
The genetic risk score was composed of single-nucleotide
polymorphisms identified in 3 meta-analyses of genome-wide
association studies of smoking quantity phenotypes.<h4>Main
outcomes and measures</h4>Smoking initiation, conversion to
daily smoking, progression to heavy smoking, nicotine
dependence (Fagerström Test of Nicotine Dependence), and
cessation difficulties were evaluated at 8 assessments
spanning the ages of 11 to 38 years.<h4>Results</h4>Genetic
risk score was unrelated to smoking initiation. However,
individuals at higher genetic risk were more likely to
convert to daily smoking as teenagers, progressed more
rapidly from smoking initiation to heavy smoking, persisted
longer in smoking heavily, developed nicotine dependence
more frequently, were more reliant on smoking to cope with
stress, and were more likely to fail in their cessation
attempts. Further analysis revealed that 2 adolescent
developmental phenotypes-early conversion to daily smoking
and rapid progression to heavy smoking-mediated associations
between the genetic risk score and mature phenotypes of
persistent heavy smoking, nicotine dependence, and cessation
failure. The genetic risk score predicted smoking risk over
and above family history.<h4>Conclusions and
relevance</h4>Initiatives that disrupt the developmental
progression of smoking behavior among adolescents may
mitigate genetic risks for developing adult smoking
problems. Future genetic research may maximize discovery
potential by focusing on smoking behavior soon after smoking
initiation and by studying young smokers.},
Doi = {10.1001/jamapsychiatry.2013.736},
Key = {fds339476}
}
@article{fds339477,
Author = {Belsky, DW and Moffitt, TE and Sugden, K and Williams, B and Houts, R and McCarthy, J and Caspi, A},
Title = {Development and evaluation of a genetic risk score for
obesity.},
Journal = {Biodemography and Social Biology},
Volume = {59},
Number = {1},
Pages = {85-100},
Year = {2013},
url = {http://dx.doi.org/10.1080/19485565.2013.774628},
Abstract = {Multi-locus profiles of genetic risk, so-called "genetic
risk scores," can be used to translate discoveries from
genome-wide association studies into tools for population
health research. We developed a genetic risk score for
obesity from results of 16 published genome-wide association
studies of obesity phenotypes in European-descent samples.
We then evaluated this genetic risk score using data from
the Atherosclerosis Risk in Communities (ARIC) cohort GWAS
sample (N = 10,745, 55% female, 77% white, 23% African
American). Our 32-locus GRS was a statistically significant
predictor of body mass index (BMI) and obesity among ARIC
whites [for BMI, r = 0.13, p<1 × 10(-30); for obesity,
area under the receiver operating characteristic curve (AUC)
= 0.57 (95% CI 0.55-0.58)]. The GRS predicted differences in
obesity risk net of demographic, geographic, and
socioeconomic information. The GRS performed less well among
African Americans. The genetic risk score we derived from
GWAS provides a molecular measurement of genetic
predisposition to elevated BMI and obesity.[Supplemental
materials are available for this article. Go to the
publisher's online edition of Biodemography and Social
Biology for the following resource: Supplement to
Development & Evaluation of a Genetic Risk Score for
Obesity.].},
Doi = {10.1080/19485565.2013.774628},
Key = {fds339477}
}
@article{fds339473,
Author = {Belsky, DW and Sears, MR and Hancox, RJ and Harrington, H and Houts, R and Moffitt, TE and Sugden, K and Williams, B and Poulton, R and Caspi,
A},
Title = {Polygenic risk and the development and course of asthma: an
analysis of data from a four-decade longitudinal
study},
Journal = {The Lancet Respiratory Medicine},
Volume = {1},
Number = {6},
Pages = {453-361},
Year = {2013},
url = {http://dx.doi.org/10.1016/S2213-2600(13)70101-2},
Abstract = {Background Genome-wide association studies (GWAS) have
discovered genetic variants that predispose individuals to
asthma. To integrate these new discoveries with emerging
models of asthma pathobiology, we aimed to test how genetic
discoveries relate to developmental and biological
characteristics of asthma. Methods In this prospective
longitudinal study, we investigated a multilocus profile of
genetic risk derived from published GWAS of asthma case
status. We then tested associations between this genetic
risk score and developmental and biological characteristics
of asthma in participants enrolled in a population-based
long-running birth cohort, the Dunedin Multidisciplinary
Health and Development Study (n=1037). We used data on
asthma onset, asthma persistence, atopy, airway
hyper-responsiveness, incompletely reversible airflow
obstruction, and asthma-related school and work absenteeism
and hospital admissions obtained during nine prospective
assessments spanning the ages of 9 to 38 years. Analyses
included cohort members of European descent from whom
genetic data had been obtained. Findings Of the 880 cohort
members included in our analysis, those at higher genetic
risk developed asthma earlier in life than did those with
lower genetic risk (hazard ratio [HR] 1·12, 95% CI
1·01–1·26). Of cohort members with childhood-onset
asthma, those with higher genetic risk were more likely to
develop life-course-persistent asthma than were those with a
lower genetic risk (relative risk [RR] 1·36, 95% CI
1·14–1·63). Participants with asthma at higher genetic
risk more often had atopy (RR 1·07, 1·01–1·14), airway
hyper-responsiveness (RR 1·16, 1·03–1·32), and
incompletely reversible airflow obstruction (RR 1·28,
1·04–1·57) than did those with a lower genetic risk.
They were also more likely to miss school or work (incident
rate ratio 1·38, 1·02–1·86) and be admitted to hospital
(HR 1·38, 1·07–1·79) because of asthma. Genotypic
information about asthma risk was independent of and
additive to information derived from cohort members’
family histories of asthma. Interpretation Our findings
confirm that GWAS discoveries for asthma are associated with
a childhood-onset phenotype. Genetic risk assessments might
be able to predict which childhood-onset asthma cases remit
and which become life-course-persistent, who might develop
impaired lung function, and the burden of asthma in terms of
missed school and work and hospital admissions, although
these predictions are not sufficiently sensitive or specific
to support immediate clinical translation.},
Doi = {10.1016/S2213-2600(13)70101-2},
Key = {fds339473}
}
@article{fds339478,
Author = {Belsky, DW and Moffitt, TE and Houts, R and Bennett, GG and Biddle, AK and Blumenthal, JA and Evans, JP and Harrington, H and Sugden, K and Williams, B and Poulton, R and Caspi, A},
Title = {Polygenic risk, rapid childhood growth, and the development
of obesity: evidence from a 4-decade longitudinal
study.},
Journal = {Arch Pediatr Adolesc Med},
Volume = {166},
Number = {6},
Pages = {515-521},
Year = {2012},
Month = {June},
url = {http://dx.doi.org/10.1001/archpediatrics.2012.131},
Abstract = {OBJECTIVE: To test how genomic loci identified in
genome-wide association studies influence the development of
obesity. DESIGN: A 38-year prospective longitudinal study of
a representative birth cohort. SETTING: The Dunedin
Multidisciplinary Health and Development Study, Dunedin, New
Zealand. PARTICIPANTS: One thousand thirty-seven male and
female study members. MAIN EXPOSURES: We assessed genetic
risk with a multilocus genetic risk score. The genetic risk
score was composed of single-nucleotide polymorphisms
identified in genome-wide association studies of
obesity-related phenotypes. We assessed family history from
parent body mass index data collected when study members
were 11 years of age. MAIN OUTCOME MEASURES: Body mass index
growth curves, developmental phenotypes of obesity, and
adult obesity outcomes were defined from anthropometric
assessments at birth and at 12 subsequent in-person
interviews through 38 years of age. RESULTS: Individuals
with higher genetic risk scores were more likely to be
chronically obese in adulthood. Genetic risk first
manifested as rapid growth during early childhood. Genetic
risk was unrelated to birth weight. After birth, children at
higher genetic risk gained weight more rapidly and reached
adiposity rebound earlier and at a higher body mass index.
In turn, these developmental phenotypes predicted adult
obesity, mediating about half the genetic effect on adult
obesity risk. Genetic associations with growth and obesity
risk were independent of family history, indicating that the
genetic risk score could provide novel information to
clinicians. CONCLUSIONS: Genetic variation linked with
obesity risk operates, in part, through accelerating growth
in the early childhood years after birth. Etiological
research and prevention strategies should target early
childhood to address the obesity epidemic.},
Doi = {10.1001/archpediatrics.2012.131},
Key = {fds339478}
}
@article{fds339474,
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},
Year = {2012},
url = {http://dx.doi.org/10.1038/mp.2012.72},
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.},
Doi = {10.1038/mp.2012.72},
Key = {fds339474}
}
@article{fds339479,
Author = {Uher, R and Caspi, A and Houts, R and Sugden, K and Williams, B and Poulton, R and Moffitt, TE},
Title = {Serotonin transporter gene moderates childhood
maltreatment's effects on persistent but not single-episode
depression: replications and implications for resolving
inconsistent results.},
Journal = {Journal of Affective Disorders},
Volume = {135},
Number = {1-3},
Pages = {56-65},
Year = {2011},
Month = {December},
url = {http://dx.doi.org/10.1016/j.jad.2011.03.010},
Abstract = {<h4>Background</h4>Genetic and environmental factors shape
life-long vulnerability to depression, but most
gene-environment interaction (G×E) research has focused on
cross-sectional assessments rather than life-course
phenotypes. This study tests the hypothesis that the G×E
involving the length polymorphism in the
serotonin-transporter-gene-linked-promoter-region (5-HTTLPR)
and childhood maltreatment is specific to depression that
runs a persistent course in adulthood.<h4>Methods</h4>The
hypothesis is tested in two cohorts. Men and women in the
Dunedin Study (N=847), New Zealand, followed to age 32 years
with 96% retention and women in the E-Risk Study (N=930),
England, followed to age 40 years with 96% retention.
Diagnoses of past-year major depressive episode were
established at four separate assessments. Depression
diagnosed on two or more occasions was considered
persistent.<h4>Results</h4>In both cohorts, statistical
tests of gene-environment interactions showed positive
results for persistent depression but not single-episode
depression. Individuals with two short 5-HTTLPR alleles and
childhood maltreatment had elevated risk of persistent but
not single-episode depression.<h4>Limitations</h4>Some cases
of recurrent depression may have been misclassified as
single-episode due to non-contiguous assessment windows, but
this would have a conservative effect on the findings.
Chronic and recurrent depression could not be reliably
distinguished due to non-contiguous periods of assessment.
Therefore, the term persistent depression is used to
describe either chronic or recurrent course.<h4>Conclusions</h4>The
specific effect on persistent depression increases the
significance of this G×E for public health. Research that
does not distinguish persistent course may underestimate
G×E effects and account for some replication failures in
G×E research.},
Doi = {10.1016/j.jad.2011.03.010},
Key = {fds339479}
}
@article{fds339480,
Author = {Danese, A and Caspi, A and Williams, B and Ambler, A and Sugden, K and Mika, J and Werts, H and Freeman, J and Pariante, CM and Moffitt, TE and Arseneault, L},
Title = {Biological embedding of stress through inflammation
processes in childhood.},
Journal = {Molecular Psychiatry},
Volume = {16},
Number = {3},
Pages = {244-246},
Year = {2011},
Month = {March},
url = {http://dx.doi.org/10.1038/mp.2010.5},
Doi = {10.1038/mp.2010.5},
Key = {fds339480}
}
@article{fds324085,
Author = {Sugden, K and Arseneault, L and Harrington, H and Moffitt, TE and Williams, B and Caspi, A},
Title = {Serotonin transporter gene moderates the development of
emotional problems among children following bullying
victimization.},
Journal = {Journal of the American Academy of Child and Adolescent
Psychiatry},
Volume = {49},
Number = {8},
Pages = {830-840},
Year = {2010},
Month = {August},
url = {http://dx.doi.org/10.1016/j.jaac.2010.01.024},
Abstract = {<h4>Objective</h4>Bullying is the act of intentionally and
repeatedly causing harm to someone who has difficulty
defending him- or herself, and is a relatively widespread
school-age phenomenon. Being the victim of bullying is
associated with a broad spectrum of emotional problems;
however, not all children who are bullied go on to develop
such problems.<h4>Method</h4>We tested the hypothesis that
the relationship between bullying victimization and
emotional problems was moderated by variation in the
serotonin transporter (5-HTT) gene in 2,232 British children
comprising the Environmental Risk (E-Risk) study
cohort.<h4>Results</h4>Our data supported the hypothesis
that children's bullying victimization leads to their
developing emotional problems, and that genetic variation in
the 5-HTTLPR moderates this relationship. Specifically,
frequently bullied children with the SS genotype were at
greater risk for developing emotional problems at age 12
than were children with the SL or LL genotype. Furthermore,
we demonstrated that this genetic moderation persisted (a)
after controlling for children's previctimization emotional
problems by assessing intraindividual change in problems
between ages 5 and 12 years, and (b) after controlling for
other risk factors shared by children growing up in the same
family by comparing emotional problems in twins discordant
for bullying victimization.<h4>Conclusions</h4>These
findings are further evidence that the 5-HTTLPR moderates
the risk of emotional disturbance after exposure to
stressful events.},
Doi = {10.1016/j.jaac.2010.01.024},
Key = {fds324085}
}
@article{fds339481,
Author = {Polanczyk, G and Caspi, A and Williams, B and Price, TS and Danese, A and Sugden, K and Uher, R and Poulton, R and Moffitt,
TE},
Title = {Protective effect of CRHR1 gene variants on the development
of adult depression following childhood maltreatment:
replication and extension.},
Journal = {Archives of General Psychiatry},
Volume = {66},
Number = {9},
Pages = {978-985},
Year = {2009},
Month = {September},
url = {http://dx.doi.org/10.1001/archgenpsychiatry.2009.114},
Abstract = {<h4>Context</h4>A previous study reported a gene x
environment interaction in which a haplotype in the
corticotropin-releasing hormone receptor 1 gene (CRHR1) was
associated with protection against adult depressive symptoms
in individuals who were maltreated as children (as assessed
by the Childhood Trauma Questionnaire [CTQ]).<h4>Objective</h4>To
replicate the interaction between childhood maltreatment and
a TAT haplotype formed by rs7209436, rs110402, and rs242924
in CRHR1, predicting adult depression.<h4>Design</h4>Two
prospective longitudinal cohort studies.<h4>Setting</h4>England
and New Zealand.<h4>Participants</h4>Participants in the
first sample were women in the E-Risk Study (N = 1116),
followed up to age 40 years with 96% retention. Participants
in the second sample were men and women in the Dunedin Study
(N = 1037), followed up to age 32 years with 96% retention.
Main Outcome Measure Research diagnoses of past-year and
recurrent major depressive disorder.<h4>Results</h4>In the
E-Risk Study, the TAT haplotype was associated with a
significant protective effect. In this effect, women who
reported childhood maltreatment on the CTQ were protected
against depression. In the Dunedin Study, which used a
different type of measure of maltreatment, this finding was
not replicated.<h4>Conclusions</h4>A haplotype in CRHR1 has
been suggested to exert a protective effect against adult
depression among research participants who reported
maltreatment on the CTQ, a measure that elicits emotional
memories. This suggests the hypothesis that CRHR1's
protective effect may relate to its function in the
consolidation of memories of emotionally arousing
experiences.},
Doi = {10.1001/archgenpsychiatry.2009.114},
Key = {fds339481}
}
@article{fds339482,
Author = {Caspi, A and Sugden, K and Moffitt, TE and Taylor, A and Craig, IW and Harrington, H and McClay, J and Mill, J and Martin, J and Braithwaite,
A and Poulton, R},
Title = {Influence of life stress on depression: moderation by a
polymorphism in the 5-HTT gene.},
Journal = {Science (New York, N.Y.)},
Volume = {301},
Number = {5631},
Pages = {386-389},
Year = {2003},
Month = {July},
url = {http://dx.doi.org/10.1126/science.1083968},
Abstract = {In a prospective-longitudinal study of a representative
birth cohort, we tested why stressful experiences lead to
depression in some people but not in others. A functional
polymorphism in the promoter region of the serotonin
transporter (5-HT T) gene was found to moderate the
influence of stressful life events on depression.
Individuals with one or two copies of the short allele of
the 5-HT T promoter polymorphism exhibited more depressive
symptoms, diagnosable depression, and suicidality in
relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study
thus provides evidence of a gene-by-environment interaction,
in which an individual's response to environmental insults
is moderated by his or her genetic makeup.},
Doi = {10.1126/science.1083968},
Key = {fds339482}
}
@article{fds339483,
Author = {Mill, JS and Caspi, A and McClay, J and Sugden, K and Purcell, S and Asherson, P and Craig, I and McGuffin, P and Braithwaite, A and Poulton,
R and Moffitt, TE},
Title = {The dopamine D4 receptor and the hyperactivity phenotype: a
developmental-epidemiological study.},
Journal = {Molecular Psychiatry},
Volume = {7},
Number = {4},
Pages = {383-391},
Year = {2002},
Month = {January},
url = {http://dx.doi.org/10.1038/sj.mp.4000984},
Abstract = {Attention-deficit hyperactivity disorder (ADHD) affects 2-6%
of school-age children and is a precursor of behavioural
problems in adolescence and adulthood. Underlying the
categorical definition of ADHD are the quantitative traits
of activity, impulsivity, and inattention which vary
continuously in the population. Both ADHD and quantitative
measures of hyperactivity are heritable, and influenced by
multiple genes of small effect. Several studies have
reported an association between clinically defined ADHD and
the seven-repeat allele of a 48-bp tandem repeat
polymorphism in the third exon of the dopamine D4 receptor
gene (DRD4). We tested this association in a large,
unselected birth cohort (n = 1037) using multiple measures
of the hyperactivity phenotype taken at multiple assessment
ages across 20 years. This longitudinal approach allowed us
to ascertain whether or not DRD4 has a general effect on the
diagnosed (n = 49) or continuously distributed hyperactivity
phenotype, and related personality traits. We found no
evidence to support this association.},
Doi = {10.1038/sj.mp.4000984},
Key = {fds339483}
}
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