Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health).

Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health).
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DOI:
10.1371/journal.pone.0148373
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Mullan Harris K
Mullan Harris K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Haberstick BC;Boardman JD;Wagner B;Smolen A;Hewitt JK;Killeya-Jones LA;Tabor J;Halpern CT;Brummett BH;Williams RB;Siegler IC;Hopfer CJ;Mullan Harris K

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5-HTTLPR-5-羟色胺转运体多态性的低转录效率短等位基因已被牵连到缓和紧张性生活事件(SLEs)和抑郁症之间的关系。尽管多次尝试重复这一观察结果,结果仍然是不确定的。我们研究了这种关系,在22岁至26岁的非西班牙裔白色男性和女性(n = 4724)参加了国家纵向研究的青少年到成人健康(添加健康)的后续信息,自1995年以来,每六年。经多重检验校正的线性和逻辑回归模型表明,携带一个或多个S等位基因的人比携带两个L等位基因的人对压力更敏感,患抑郁症的风险更高。这种关系表现在剂量反应的方式,抑郁症的风险是最大的那些谁报告经历了更多的SLE。在事后分析中,我们无法复制自杀意念的相互作用效应,但确实发现了暗示性证据,表明SLE和5 HTTLPR对男性和女性自杀意念的影响不同。儿童期虐待没有影响。我们的研究结果为最初的假设提供了部分支持,即5-HTTLPR基因型与青年期抑郁症病因学中压力性生活事件的经历相互作用。然而,即使有这么大的样本,以及精心构建的先验分析计划,结果仍然不是确定的。为了复制的目的,需要在其他大型数据集中用广泛的环境和抑郁措施来表征5 HTTLPR。
The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.