Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.
Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress I: Effects in males and females.
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DOI：
10.1016/j.psyneuen.2015.12.023
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发表时间：
2016-08
影响因子：
3.7
通讯作者：
Vrshek-Schallhorn S
中科院分区：
文献类型：
--
作者：
Avery BM;Vrshek-Schallhorn S
遗传对应激反应的影响可能为抑郁症风险机制提供见解。rs6318的C等位基因是HTR 2C基因内的一种puerectin功能多态性，据报道，该等位基因可预测对实验室诱导的应激的更高皮质醇和负性情感反应。然而，尽管HTR 2C的X-连锁，性别的潜在调节作用还没有被检查。我们假设性别调节rs6318对皮质醇和实验室诱导压力的情感反应的影响，男性表现出更强的影响。通过临床访谈筛选的非抑郁年轻人（N = 112; 39名女性）提供了DNA样本，并完成了阴性评价性特里尔社会压力测试或非评价性对照方案。唾液皮质醇和自我报告的影响进行了评估，在四个时间点。与假设相反，在多水平模型中，C-携带者对实验室诱导的应激表现出迟钝而不是夸大的皮质醇反应（B = 0.467，p < 0.001），当共变亚临床抑郁症状时，这种反应持续存在。这种效应不受性别（B = 0.174，p = 0.421）的调节，并且在分别检查女性（B = 0.362，p = 0.013）和男性（B = 0.537，p < 0.001）时仍然显著。当共变亚临床抑郁症状时，C基因携带者在应对压力时表现出比非携带者更大的消极自我关注情绪反应性（B =-0.360，p = 0.067），并且表现出比非携带者更高水平的亚临床抑郁症状（F = 6.463，p = 0.012）。研究结果支持rs6318 C等位基因在应激反应失调中的作用，并表明C等位基因可能导致抑郁症的风险。
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 depression 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 depression symptoms (b = −0.360, p = 0.067), and exhibited higher levels of subclinical depression 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.