title: A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Brummett
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Babyak
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
authors.affiliation: Department of Sociology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Carolina Population Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Kathleen Mullan
authors.initials: KM
authors.lastname: Harris
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Duke Molecular Physiology Institute and Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Abanish
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Costa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Georgiades
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Ilene C
authors.initials: IC
authors.lastname: Siegler
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012737:Sex Factors; D013315:Stress, Psychological / Q000235:genetics / Q000473:pathology*; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D006854:Hydrocortisone