The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression - A replication
The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression - A replication
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DOI：
10.1001/archpsyc.62.5.529
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发表时间：
2005-05-01
影响因子：
--
通讯作者：
Riley, B
中科院分区：
文献类型：
--
作者：
Kendler, KS;Kuhn, JW;Riley, B
背景：先前来自双胞胎研究的证据表明，压力性生活事件（SLEs）的致抑郁效应具有遗传调节作用。是否可以鉴定出参与这种效应的特定基因？目的：为了复制和扩展最近的一项研究，即5-羟色胺转运体（5-HTT）的功能变异可能部分解释这些发现。设计：将过去一年中重度抑郁症和广泛性焦虑综合征的风险表征为5-HTT基因型、性别、SLE的发生率和SLE相关威胁水平的评级的函数。549例男性和女性双胞胎，平均年龄为34.9岁（SD 9.1）.主要结果测量：过去一年中严重抑郁症和广泛性焦虑综合征的发作，发病时间测量到最近的一个月。在5-HTT基因座上具有2个短（S）等位基因的个体比具有1个或2个长（L）等位基因的个体对所有SLE的致抑郁效应更敏感。当SLE相关的威胁水平进行了检查，基因型和SLE之间的相互作用导致SS个体的敏感性增加，常见的低威胁事件的抑郁症的影响。这些事件对具有SL和LL基因型的人的风险影响很小。5-HTT基因型没有修改的影响，SLE的风险广泛性焦虑syndrome.Conclusion：在5-HTT的变化缓和的敏感性，个人的SLE的抑郁症的影响很大程度上通过生产，在SS个人，增加敏感性的影响，轻度的压力。需要重复这些有趣的结果。
Context: Prior evidence from twin studies suggested genetic moderation of the depressogenic effects of stressful life events (SLEs). Can the specific genes involved in this effect be identified?Objective: To replicate and extend a recent study that a functional variant in the serotonin transporter (5-HTT) might in part explain these findings.Design: Characterizing risk for major depression and generalized anxiety syndrome in the last year as a function of 5-HTT genotype, sex, and the occurrence of SLEs and ratings of the SLE-associated level of threat.Setting: A population-based sample of adult twinsParticipants: Five hundred forty-nine male and female twins with a mean age at participation of 34.9 years (SD 9.1).Main Outcome Measure: Episodes of major depres-sion and generalized anxiety syndrome in the last year with onset measured to the nearest month.Results: Individuals with 2 short (S) alleles at the 5-HTT locus were more sensitive to the depressogenic effects of all SLEs than were those with 1 or 2 long (L) alleles. When level of SLE-associated threat was examined, the interaction between genotype and SLE resulted from an increased sensitivity of SS individuals to the depressogenic effects of common low-threat events. These events had little impact on risk for those possessing the SL and LL genotypes. The 5-HTT genotype did not modify the effects of SLEs on risk for generalized anxiety syndrome.Conclusion: Variation at the 5-HTT moderates the sensitivity of individuals to the depressogenic effects of SLEs largely by producing, in SS individuals, an increased sensitivity to the impact of mild stressors. Replication of these intriguing results is needed.