Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood
Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood
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DOI：
10.1016/j.euroneuro.2013.12.001
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发表时间：
2014-06-01
影响因子：
5.6
通讯作者：
Laucht, Manfred
中科院分区：
文献类型：
--
作者：
Buchmann, Arlette F.;Holz, Nathalie;Laucht, Manfred
最近的研究表明，FKBP5（一种糖皮质激素受体，调节共同伴侣）在抑郁症和焦虑症等压力相关疾病的发展中起着重要作用。本研究旨在通过研究FKBP5 rs1360780基因型和童年逆境的不同测量是否相互作用来预测应激诱导的皮质醇分泌，从而复制和扩展先前的证据，表明FKBP5多态性调节下丘脑-垂体-肾上腺（HPA）功能。在19岁时，195名年轻人（90名男性，105名女性）参加了一项流行病学队列研究，完成了特里尔社会压力测试（TSST）来评估皮质醇应激反应，并对FKBP5 rs1360780进行了基因分型。童年逆境评估使用童年创伤问卷（CTQ）和标准化的父母访谈产生的家庭逆境指数。通过回顾性自我报告（CTQ）评估，基因型和童年逆境对应激皮质醇反应的影响显著，但对前瞻性确定的客观家庭逆境影响不显著。在rs1360780 CC基因型携带者中，儿童虐待的严重程度与皮质醇水平的降低显著相关，而在T等位基因携带者中则没有这种影响。这些发现表明FKBP5的功能参与了与儿童虐待相关的神经内分泌应激调节的长期改变，这被认为是应激相关疾病背景下的发病前风险或恢复因素。(C) 2013 Elsevier B.V.和ECNR这是一篇基于CC BY-NC-ND许可的开放获取文章。
Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license.