Do 5HTTLPR and Stress Interact in Risk for Depression and Suicidality? Item Response Analyses of a Large Sample
Do 5HTTLPR and Stress Interact in Risk for Depression and Suicidality? Item Response Analyses of a Large Sample
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DOI：
10.1002/ajmg.b.31044
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发表时间：
2010-04-01
影响因子：
2.8
通讯作者：
Wray, Naomi R.
中科院分区：
文献类型：
--
作者：
Coventry, William L.;James, Michael R.;Wray, Naomi R.
5 -羟色胺转运基因（SLC6A4）长度多态性（5HTTLPR）与抑郁症应激性生活事件之间的相互作用已被报道，导致许多尝试重复，但结果不一致。这种不一致可能部分反映了小样本量和长等位基因SNP rs25531的未知贡献。本研究采用顺序回归和项目反应理论分析，从2230个18-95岁家庭中选取3243名个体（平均32.3岁，SD = 13.6），研究了5HTTLPR （SNP亚型rs25531）与压力事件对抑郁和自杀风险的相互作用。参与者通过邮寄问卷（82%的回复率）报告了过去12个月的压力事件和抑郁症状。压力事件被定义为“个人”（影响个人）或“网络”（影响亲密的家人或朋友）。1至10年后（平均4.2年），参与者完成了全面的临床精神病学电话访谈（83%的应答率），评估了DSM-IV的重度抑郁和自杀意念。在控制了年龄和性别后，临床访谈评估的抑郁自我报告和抑郁/自杀倾向的增加与先前的个人事件显著相关（P < 0.001）。然而，它们与先前的网络事件不一致（范围从ns到P < 0.01），并且与任何基因型主要效应（5HTTLPR, 5HTTLPR rs25531）或相互作用（应激x基因型）没有显著相关。我们没有发现任何证据支持任何5HTTLPR基因型通过应激相互作用的假设。(C) 2009 Wiley-Liss, Inc。
The reported interaction between the length polymorphism (5HTTLPR) in the serotonin transporter gene (SLC6A4) and stressful life events on depression has led to many attempts to replicate but with inconsistent results. This inconsistency may reflect, in part, small sample size and the unknown contribution of the long allele SNP, rs25531. Using a large twin sample of 3,243 individuals from 2,230 families aged 18-95 years (mean = 32.3, SD = 13.6) we investigate the interaction between 5HTTLPR (subtyped with SNP rs25531) and stressful events on risk of depression and suicidality using both ordinal regressions and item response theory analyses. Participants reported via mailed questionnaire (82% response rate) both stressful events in the preceeding 12 months and symptoms of depression. Stressful events were defined as "personal" (affecting the individual), or "network" (affecting close family or friends). One to 10 years later (mean = 4.2 years), participants completed a comprehensive clinical psychiatric telephone interview (83% response rate) which assessed DSM-IV major depression and ideation of suicidality. Self-reports of depression and an increase in depression/suicidality assessed by clinical interview are significantly associated with prior personal events (P < 0.001) after controlling for age and sex. However, they are inconsistently associated with prior network events (ranging, ns to P < 0.01) and are not significantly associated with any of the genotype main effects (5HTTLPR, 5HTTLPR rs25531) or interactions (stress x genotype). We find no evidence to support the hypothesis of any 5HTTLPR genotype by stress interaction. (C) 2009 Wiley-Liss, Inc.