Anguelova M, Benkelfat C, Turecki G
Douglas Hospital Research Center, McGill University, Montreal, Canada.
Mol Psychiatry. 2003 Jun;8(6):574-91. doi: 10.1038/sj.mp.4001328.
The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). They have been investigated in a number of allelic association studies where the individual results have been inconsistent, and therefore, definite conclusions are difficult to make. Systematic reviews using meta-analytical techniques are a reliable method for objectively and reproducibly assessing individual studies and generating combined result. This study aimed at reviewing published studies investigating the association between affective disorders (MDD and BD) and variation at genes coding for serotonin receptors and the serotonin transporter. We performed National Library of Medicine database searches to identify potential studies. More than 430 articles were reviewed and 86 studies met the inclusion criteria for participation in our review. Of these, 41 studies investigated 45 different 5-HT receptor variants and 45 studies investigated at least one of two commonly studied 5-HTT polymorphisms in MDD. Many studies investigated the association between MDD and BD with the 5-HT2A 102 T/C, the 5-HTT promoter 44 bp insertion/deletion and the intron 2 VNTR polymorphisms, and thus, these could be pooled using meta-analytic techniques. The overall odds ratio (OR) for the combined individual results was significant for BD and the two 5-HTT polymorphisms: Mantel-Haenszel weighted OR=1.14, CI: 1.03-1.26, P=0.015 for the promoter locus (N=3467) and Mantel-Haenszel Weighted odds ratio OR=1.18, CI: 1.05-1.32, P=0.004 for the VNTR locus (N=3620). However, sensitivity analysis indicated that, in each case, the overall positive association could be mostly attributed to the large effect of one individual study. Therefore, these results suggest that, although promising, further studies are required to assess appropriately the evidence suggesting an association between BD and 5-HTT.
包括5-羟色胺转运体（5-HTT）在内的不同5-羟色胺（血清素）受体是诸如重度抑郁症（MDD）和双相情感障碍（BD）等情感障碍的候选基因。在许多等位基因关联研究中对它们进行了调查，各个研究结果并不一致，因此难以得出明确结论。运用荟萃分析技术进行系统评价是客观且可重复地评估个体研究并得出综合结果的可靠方法。本研究旨在回顾已发表的关于情感障碍（MDD和BD）与编码血清素受体及血清素转运体的基因变异之间关联的研究。我们在国立医学图书馆数据库进行检索以识别潜在研究。共审查了430多篇文章，86项研究符合参与我们综述的纳入标准。其中，41项研究调查了45种不同的5-羟色胺受体变体，45项研究调查了MDD中两种常见的5-HTT多态性中的至少一种。许多研究调查了MDD和BD与5-HT2A 102 T/C、5-HTT启动子44 bp插入/缺失及内含子2 VNTR多态性之间的关联，因此，可以运用荟萃分析技术对这些研究进行汇总。BD及两种5-HTT多态性的个体研究综合结果的总体比值比（OR）具有统计学意义：启动子位点的Mantel-Haenszel加权OR = 1.14，CI：1.03 - 1.26，P = 0.015（N = 3467）；VNTR位点的Mantel-Haenszel加权比值比OR = 1.18，CI：1.05 - 1.32，P = 0.004（N = 3620）。然而，敏感性分析表明，在每种情况下，总体正相关大多可归因于一项个体研究的巨大影响。因此，这些结果表明，尽管前景可期，但仍需要进一步研究以适当评估表明BD与5-HTT之间存在关联的证据。
