Cortisol responses to chronic stress in adult macaques: Moderation by a polymorphism in the serotonin transporter gene

Accumulating evidence has shown that a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the association between stress and depressive symptoms. However, the exact etiologies underlying this moderation are not well understood. Here it is reported that among adult female rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) exerted an influence on cortisol responses to chronic stress. It was found that females with two copies of the short allele were associated with increased cortisol responses to chronic stress in comparison to their counterparts who have one or two copies of the long allele. In the absence of stress, no differences related to genotype were observed in these females. This genetic moderation was found without a genetic influence on exposure to stressful situations. Rather it was found to be a genetic modulation of cortisol responses to chronic stress. These findings indicate that the rh5-HTTLPR polymorphism is closely related to hypothalamus pituitary adrenal (HPA) axis reactivity, which may increase susceptibility to depression in females with low serotonin transporter efficiency and a history of stress. (C) 2014 Elsevier B.V. All rights reserved.

越来越多的证据表明，血清素转运体基因（5 - HTTLPR）启动子区域的一种多态性会调节压力与抑郁症状之间的关联。然而，这种调节作用的确切病因尚不清楚。在此有报道称，在成年雌性恒河猴中，一种同源多态性（rh5 - HTTLPR）对皮质醇对慢性压力的反应产生了影响。研究发现，与拥有一个或两个长等位基因拷贝的同类相比，拥有两个短等位基因拷贝的雌性恒河猴对慢性压力的皮质醇反应增强。在没有压力的情况下，这些雌性恒河猴在基因型相关方面没有差异。这种基因调节作用是在对压力情境暴露没有基因影响的情况下发现的，而是对皮质醇对慢性压力反应的一种基因调控。这些发现表明，rh5 - HTTLPR多态性与下丘脑 - 垂体 - 肾上腺（HPA）轴的反应性密切相关，这可能会增加血清素转运体效率低且有压力史的雌性患抑郁症的易感性。（C）2014爱思唯尔有限公司。保留所有权利。