Wang Qingzhong, Shelton Richard C, Dwivedi Yogesh
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Affect Disord. 2018 Jan 1;225:422-428. doi: 10.1016/j.jad.2017.08.066. Epub 2017 Aug 24.
Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD.
A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted.
Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD.
The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size.
These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD.
基因-环境相互作用会增加患精神疾病的风险。FKBP5基因变异与早期生活压力之间的相互作用可能不仅会增加患情绪障碍的风险,还会增加许多其他行为表型的风险。本研究的目的是回顾并对已发表的研究结果进行荟萃分析,这些研究探讨了FKBP5基因变异与早期生活压力之间的相互作用及其与应激相关障碍(如重度抑郁症和创伤后应激障碍)的关联。
使用PsychINFO和PubMed数据库进行文献检索,截至2017年5月。共有14项研究,总计15109名参与者符合纳入标准,将这些研究结果合并,并以相关性差异作为效应量进行荟萃分析。根据文献,在FKBP5基因内选择了rs1360780、rs3800373和rs9470080单核苷酸多态性(SNP)并进行系统评价。
基于综合荟萃分析软件,未检测到发表偏倚。敏感性分析和荟萃分析结果的可信度也表明分析是稳定的。荟萃分析表明,携带rs1360780的T等位基因、rs3800373的C等位基因或rs9470080的T等位基因且暴露于早期生活创伤的个体患抑郁症或创伤后应激障碍的风险更高。
由于样本量有限,未考察种族、年龄、性别和不同应激测量方法的影响。
这些结果为FKBP5基因型与早期生活压力之间的相互作用提供了有力证据,这可能是重度抑郁症和创伤后应激障碍等应激相关障碍的一个重要危险因素。