Nonsynonymous HTR2C Polymorphism Predicts Cortisol Response to Psychosocial Stress I: Effects in Males and Females

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Suzanne Vrshek-Schallhorn, Associate Professor and Undergraduate Program Director (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Background Genetic influences on stress reactivity may provide insight into depression risk mechanisms. The C-allele of rs6318, a putatively functional polymorphism located within the HTR2C gene, has been reported to predict greater cortisol and negative affective reactivity to lab-induced stress. However, the potential moderating effect of sex has not been examined despite X-linkage of HTR2C. We hypothesized that sex moderates the effect of rs6318 on cortisol and affective reactivity to lab-induced stress, with males showing stronger effects.Methods Non-depressed young adults (N = 112; 39 female) screened via clinical interview provided a DNA sample and completed either a negative evaluative Trier Social Stress Test, or a non-evaluative control protocol. Salivary cortisol and self-reported affect were assessed at four timepoints.Results Contrary to hypotheses, C-carriers showed blunted rather than exaggerated cortisol responses to lab-induced stress in multilevel models (b = 0.467, p < 0.001), which persisted when covarying subclinical depressive symptoms. This effect was not moderated by sex (b = 0.174, p = 0.421), and remained significant when examining females (b = 0.362, p = 0.013) and males (b = 0.537, p < 0.001) separately. C-carriers also exhibited marginally greater reactivity in negative self-focused affect in response to stress than non-carriers when covarying subclinical depressive symptoms (b = -0.360, p = 0.067), and exhibited higher levels of subclinical depressive symptoms than non-carriers (F = 6.463, p = 0.012).Conclusions Results support a role for the rs6318 C-allele in dysregulated stress responding, and suggest that the C-allele may contribute to risk for depression.

Additional Information

Psychoneuroendocrinology 70
Language: English
Date: 2016
rs6318, cortisol, serotonin, gene-environement interaction, lab-induced stress, major depressive disorder

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