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A Putatively Functional Polymorphism in the

Citation

Brummett, Beverly H.; Babyak, Michael A.; Williams, Redford B.; Harris, Kathleen Mullan; Jiang, Rong; Kraus, William E.; Singh, Abanish; Costa, Paul T.; Georgiades, Anastasia; & Siegler, Ilene C. (2014). A Putatively Functional Polymorphism in the. PLOS ONE, 9(12), e114451. PMCID: PMC4267787

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.

URL

http://dx.doi.org/10.1371/journal.pone.0114451

Reference Type

Journal Article

Year Published

2014

Journal Title

PLOS ONE

Author(s)

Brummett, Beverly H.
Babyak, Michael A.
Williams, Redford B.
Harris, Kathleen Mullan
Jiang, Rong
Kraus, William E.
Singh, Abanish
Costa, Paul T.
Georgiades, Anastasia
Siegler, Ilene C.

PMCID

PMC4267787