title: Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Avery
authors.affiliation: Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC, USA; Department of Psychology, Northwestern University, Evanston, IL, USA. Electronic address: Suzanne.Schallhorn@uncg.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vrshek-Schallhorn
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D003863:Depression / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D006854:Hydrocortisone
keywords: Cortisol; Gene-environment interaction; Lab-induced stress; Major depressive disorder; Serotonin; rs6318