A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.
Date
2014-01
Editor
Walss-Bass, Consuelo
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Abstract
Psychosocial stress is well known to be positively associated with subsequent depressive
symptoms. Cortisol response to stress may be one of a number of biological mechanisms
that links psychological stress to depressive symptoms, although the precise causal
pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also
been shown to be associated with depression and with clinical response to antidepressant
medications. We recently demonstrated that variation in a single nucleotide polymorphism
on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release
and short-term changes in affect in response to a series of stress tasks in the laboratory.
Based on this observation, we decided to examine whether rs6318 might moderate the
association between psychosocial stress and subsequent depressive symptoms. In the
present study we use cross-sectional data from a large population-based sample of
young adult White men (N = 2,366) and White women (N = 2,712) in the United States
to test this moderation hypothesis. Specifically, we hypothesized that the association
between self-reported stressful life events and depressive symptoms would be stronger
among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers.
In separate within-sex analyses a genotype-by-life stress interaction was observed
for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported
high levels of life stress had depressive symptom scores that were about 0.3 standard
deviations higher than female Cys23 G carriers with similarly high stress levels.
In contrast, no appreciable difference in depressive symptoms was observed between
genotypes at lower levels of stress. Our findings support prior work that suggests
a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms
in White women with a history of significant life stress.
Type
Journal articleSubject
HumansHydrocortisone
Receptor, Serotonin, 5-HT2C
Cross-Sectional Studies
Stress, Psychological
Depressive Disorder
Sex Factors
Genotype
Polymorphism, Single Nucleotide
Adult
European Continental Ancestry Group
United States
Female
Male
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https://hdl.handle.net/10161/17608Published Version (Please cite this version)
10.1371/journal.pone.0114451Publication Info
Brummett, Beverly H; Babyak, Michael A; Williams, Redford B; Harris, Kathleen Mullan;
Jiang, Rong; Kraus, William E; ... Siegler, Ilene C (2014). A putatively functional polymorphism in the HTR2C gene is associated with depressive
symptoms in white females reporting significant life stress. PloS one, 9(12). pp. e114451. 10.1371/journal.pone.0114451. Retrieved from https://hdl.handle.net/10161/17608.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Michael Alan Babyak
Professor Emeritus in Psychiatry and Behavioral Sciences
Since coming to Duke as an intern in 1994 I have collaborated as a biostatistician
and co-investigator at Duke on numerous observational and experimental studies involving
behavior, psychosocial factors, health, and disease. The substantive topics have ranged
across questions concerning exercise and depression, hypertension, weight loss, the
genetics of stress and heart disease, sickle cell disease, to name a few. I am particularly
interested in the issue of improving reproducibility and transpa
Beverly H. Brummett
Associate Professor Emeritus in Psychiatry and Behavioral Sciences
In the early part of my career, my work generally focused on examining psychosocial
determinants or correlates (e.g., emotion, personality, and socioeconomic status)
of cardiovascular disease. However, in the past several years, my work has also expanded
to include examining how stressful emotional responses, combined with proposed genetic
markers, influence metabolic functioning, cognitive decline, functional capacity and
quality of live in the elderly, depressive symptomology, and maj
Paul T. Costa Jr.
Adjunct Professor in the Department of Psychiatry and Behavioral Sciences
Anastasia Georgiades
Research Scientist
Dr Georgiades research has focused on evaluating bio-behavioral risk-factors, in particular
the role mental stress, in the development of diabetes and cardiovascular disease.
She have written and co-authored over 45 papers in the area of behavioral medicine
and have vast experience from designing experimental studies and evaluating epidemiological
cohort studies. In addition, she has been co-investigator on intervention studies
examining the effects of cognitive behavioral therapy, stress man
Rong Jiang
Assistant Professor in Psychiatry and Behavioral Sciences
William Erle Kraus
Richard and Pat Johnson University Distinguished Professor
My training, expertise and research interests range from human integrative physiology
and genetics to animal exercise models to cell culture models of skeletal muscle adaptation
to mechanical stretch. I am trained clinically as an internist and preventive cardiologist,
with particular expertise in preventive cardiology and cardiac rehabilitation. My
research training spans molecular biology and cell culture, molecular genetics, and
integrative human exercise physiology and metabolism. I pr
Ilene C. Siegler
Professor in Psychiatry and Behavioral Sciences
My research efforts are in the area of developmental health psychology and organized
around understanding the role of personality in health and disease in middle and later
life. My primary research activity is as Principal Investigator of the UNC Alumni
Heart Study (UNCAHS) a prospective epidemiologic study of 5000 middle aged men and
women and 1200 of their spouses that evaluates the role of personality on coronary
heart disease and coronary heart disease risk, cancer, and normal a
Abanish Singh
Assistant Professor of Psychiatry and Behavioral Sciences
With a unique skill set resulting from outstanding training, my sole aim was to help
improve human health through cutting-edge translational research. Specifically, I
have been interested in illuminating the mechanisms responsible for the causes and
progression of the leading public health conditions, which may help with the development
and enhancement of precision medicine. As part of this endeavor, I also became interested
in studying the measurement of biobehavioral risk factors and
Redford B. Williams Jr.
Professor Emeritus of Psychiatry and Behavioral Sciences
My research aims to identify psychosocial factors that are involved in the pathogenesis
and course of major medical disorders, to characterize the biobehavioral mechanisms
whereby such factors influence disease, and to develop both behavioral and pharmacologic
means of preventing or ameliorating the adverse impact of psychosocial factors on
health and disease. Specific projects that are currently active include: 1) The influence
of hostile personality, social isolation, depression and other psyc
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