Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques
Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques
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DOI：
10.1073/pnas.0403763101
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发表时间：
2004-08-17
影响因子：
11.1
通讯作者：
Higley, JD
中科院分区：
文献类型：
--
作者：
Barr, CS;Newman, TK;Higley, JD
人类血清素转运体基因启动子（5 - HTTLPR）的一种多态性与焦虑相关，并且在面临逆境时患抑郁症的风险增加。在此，我们报告在幼年恒河猴中，一种直系同源多态性（rh5 - HTTLPR）与以同伴抚养形式出现的逆境相互作用，影响促肾上腺皮质激素（ACTH）对压力的反应，而且这种相互作用存在性别差异。在雄性中，I/s型个体对分离的ACTH反应高于I/I型个体。然而，在雌性中，只有有逆境经历的个体，s等位基因才与对压力的ACTH反应增加有关。有趣的是，同伴抚养的动物，特别是携带s等位基因的雌性，对压力的皮质醇反应也较低，这种模式已被认为与某些与压力相关的神经精神疾病有关。由此推断，我们的研究结果表明一种有趣的可能性，即携带5 - HTTLPR s等位基因的人类女性可能更容易受到早期逆境的影响。这种相互作用效应可能是女性某些与压力相关疾病发病率增加的基础。
A polymorphism in the human serotonin transporter gene promoter (5-HTTLPR) is associated with anxiety and increased risk for developing depression in the face of adversity. Here, we report that among infant rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) interacts with adversity in the form of peer rearing to influence adrenocorticotropic hormone (ACTH) response to stress and, further, that this interaction is sexually dichotomous. ACTH responses to separation are higher in I/s than in I/I males. in females, however, it is only among those with a history of adversity that the s allele is associated with increased ACTH responses to stress. Of interest, peer-reared animals, in particular females carrying the s allele, also exhibit lower cortisol responses to stress, a pattern that has been recognized in association with certain stress-related neuropsychiatric disorders. By extension, our findings suggest the intriguing possibility that human females carrying the 5-HTTLPR s allele could be more vulnerable to the effects of early adversity. This interactive effect may underlie the increased incidence of certain stress-related disorders in women.