Research paperInteraction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis

- First meta-analysis on FKBP5 gene variants, early-life stress and PTSD and MDD.
- Strong association between FKBP variants, early-life stress and depression/PTSD.
- HPA axis and FKBP5 genes confer sensitivity to early environmental factors.
- FKBP5 gene variants may play a role in the development of depression and PTSD.

BackgroundGene-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.MethodsA 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.ResultsBased 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.LimitationsThe effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size.ConclusionsThese 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.