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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.

SUBMITTER: Avery BM

PROVIDER: S-EPMC4948185 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.

Avery Bradley M BM Vrshek-Schallhorn Suzanne S

Psychoneuroendocrinology 20151224

<h4>Background</h4>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 ...[more]

PMID: 26787298

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Project description:Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9-12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11-14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset.

Project description:As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one's time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms) and long (1,600 ms) visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group), individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the understanding of the relationship between stress and temporal sensitivity.

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Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.

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Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.

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