The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation.
The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation.
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DOI：
10.1001/archgenpsychiatry.2010.189
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发表时间：
2011-05
影响因子：
--
通讯作者：
Sen, Srijan
中科院分区：
文献类型：
--
作者：
Karg, Katja;Burmeister, Margit;Shedden, Kerby;Sen, Srijan
关于5-羟色胺转运蛋白启动子多态性（5-HTTLPR）与抑郁症发展中压力之间相互作用的初步报告可能是精神遗传学中最著名和引用最多的发现。最近的两项荟萃分析探讨了试图复制这一初步报告的研究，并得出结论，证据不支持相互作用的存在。然而，即使是更大的荟萃分析也只包括了56项研究中的14项，这些研究探讨了5-HTTLPR，压力和抑郁之间的关系。我们试图进行一项荟萃分析，包括所有相关研究，评估5-HTTLPR是否调节压力和抑郁之间的关系。我们从之前的荟萃分析和综述以及PubMed数据库检索中识别出相关文章。我们排除了两项研究，这些研究提供的数据已被纳入我们的荟萃分析中的其他更大的研究中，以避免重复计算受试者。为了进行更具包容性的荟萃分析，我们使用Liptak-Stouffer Z评分法在显著性检验水平而非原始数据水平上结合联合收割机的主要研究结果。我们纳入了54项研究，发现了强有力的证据表明5-HTTLPR调节了压力和抑郁之间的关系，5-HTTLPR s等位基因与压力下抑郁症发生风险增加相关（p<0.0001）。当我们的分析仅限于之前荟萃分析中的研究时，我们没有发现相关性的证据（Munafo研究p=0.16; Risch研究p=0.11）。这表明，以前的荟萃分析和我们的结果之间的差异不是由于荟萃分析技术的差异，而是由于本分析中包括的扩展研究集。与早期较小的荟萃分析结果相反，我们发现了强有力的证据，即5-HTTLPR在迄今为止发表的研究中缓和了压力和抑郁之间的关系。
The initial report of an interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression is perhaps the best-known and most cited finding in psychiatric genetics. Two recent meta-analyses explored the studies seeking to replicate this initial report and concluded that the evidence did not support the presence of the interaction. However, even the larger of the meta-analyses included only 14 of the 56 studies that have explored the relationship between 5-HTTLPR, stress and depression. We sought to perform a meta-analysis including all relevant studies assessing whether 5-HTTLPR moderates the relationship between stress and depression. We identified relevant articles from previous meta-analyses and reviews and a PubMed database search. We excluded two studies presenting data that were included in other, larger, studies already included in our meta-analysis to avoid duplicate counting of subjects. In order to perform a more inclusive meta-analysis, we used the Liptak-Stouffer Z-score method to combine findings of primary studies at the significance test level rather than raw data level. We included 54 studies and found strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the 5-HTTLPR s allele associated with an increased risk of developing depression under stress (p<0.0001). When restricting our analysis to the studies included in the previous meta-analyses, we found no evidence of association (Munafo studies p=0.16; Risch studies p=0.11). This suggests that the difference in results between previous meta-analyses and ours was not due to the difference in meta-analytic technique but instead to the expanded set of studies included in this analysis. Contrary to the results of the smaller earlier meta-analyses, we find strong evidence that 5-HTTLPR moderates the relationship between stress and depression in the studies published to date.
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影响因子：
6.6
作者：
Grassi, Luigi;Rossi, Elena;Giraldi, Tullio
通讯作者：
Giraldi, Tullio
影响因子：
10.6
作者：
Heinz, Andreas;Smolka, Michael N.;Weinberger, Daniel R.
通讯作者：
Weinberger, Daniel R.
DOI：
10.1111/j.1469-7610.2009.02149.x
发表时间：
2010-02
期刊：
Journal of child psychology and psychiatry, and allied disciplines
影响因子：
--
作者：
Benjet C;Thompson RJ;Gotlib IH
通讯作者：
Gotlib IH
DOI：
10.1002/ajmg.b.31044
发表时间：
2010-04-01
影响因子：
2.8
作者：
Coventry, William L.;James, Michael R.;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
2.6
作者：
Aslund, Cecilia;Leppert, Jerzy;Nilsson, Kent W.
通讯作者：
Nilsson, Kent W.