Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.
Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.
Neurosci Biobehav Rev. 2017 Apr;75:129-139. doi: 10.1016/j.neubiorev.2017.01.028. Epub 2017 Jan 27.
Late-life depression (LLD) is thought to be multifactorial in etiology, including a significant genetic component. While a number of candidate gene studies have been carried out, results remain inconclusive. We undertook a systematic review of all genetic association studies of depression or depressive symptoms in late life published before February 2016, and performed meta-analyses on polymorphisms investigated in three or more independent studies. A total of 46 candidate gene studies examining 56 polymorphisms in 23 genes as well as a genome-wide association study (GWAS) were included. Meta-analyses were conducted for four polymorphisms using random effects models, of which three (APOE, BDNF, SLC6A4) were associated with LLD. These genes are implicated in hippocampal plasticity and stress reactivity, suggesting that dysregulation of these pathways may contribute to LLD. Despite using a large sample, the only GWAS published to date identified only one genome-wide significant locus in the 5q21 region. In the future, larger genetic studies specifically examining LLD, including non-hypothesis-driven GWAS, are required to further identify genetic determinants of LLD.
老年期抑郁症（LLD）的病因被认为是多因素的，包括一个重要的遗传成分。虽然已经进行了许多候选基因研究，但结果仍不确定。我们对截至 2016 年 2 月之前发表的所有关于老年期抑郁症或抑郁症状的遗传关联研究进行了系统评价，并对三个或更多独立研究中研究的多态性进行了荟萃分析。共纳入了 46 项候选基因研究，研究了 23 个基因中的 56 个多态性，以及一项全基因组关联研究（GWAS）。使用随机效应模型对四个多态性进行了荟萃分析，其中三个（APOE、BDNF、SLC6A4）与 LLD 相关。这些基因与海马体可塑性和应激反应有关，表明这些通路的失调可能导致 LLD。尽管使用了较大的样本量，但迄今为止发表的唯一 GWAS 仅在 5q21 区域确定了一个全基因组显著位点。未来，需要进行更大规模的专门针对 LLD 的遗传研究，包括非假设驱动的 GWAS，以进一步确定 LLD 的遗传决定因素。
