A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere114451
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 16 2014
Externally publishedYes

Fingerprint

Polymorphism
Psychological Stress
Genes
genetic polymorphism
Depression
cortisol
Hydrocortisone
genes
life events
antidepressants
genotype
young adults
serotonin
Antidepressive Agents
single nucleotide polymorphism
drug therapy
Single Nucleotide Polymorphism
stress response
Nucleotides
Genotype

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Brummett, B. H., Babyak, M. A., Williams, R. B., Harris, K. M., Jiang, R., Kraus, W. E., ... Siegler, I. 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), [e114451]. https://doi.org/10.1371/journal.pone.0114451

A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress. / Brummett, Beverly H.; Babyak, Michael A.; Williams, Redford B.; Harris, Kathleen Mullan; Jiang, Rong; Kraus, William E.; Singh, Abanish; Costa, Paul; Georgiades, Anastasia; Siegler, Ilene C.

In: PLoS One, Vol. 9, No. 12, e114451, 16.12.2014.

Research output: Contribution to journalArticle

Brummett, BH, Babyak, MA, Williams, RB, Harris, KM, Jiang, R, Kraus, WE, Singh, A, Costa, P, Georgiades, A & Siegler, IC 2014, 'A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress', PLoS One, vol. 9, no. 12, e114451. https://doi.org/10.1371/journal.pone.0114451
Brummett, Beverly H. ; Babyak, Michael A. ; Williams, Redford B. ; Harris, Kathleen Mullan ; Jiang, Rong ; Kraus, William E. ; Singh, Abanish ; Costa, Paul ; Georgiades, Anastasia ; Siegler, Ilene C. / A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress. In: PLoS One. 2014 ; Vol. 9, No. 12.
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