FKBP5 methylation, psychiatric disorders and stress: a systematic review and synthesis

Abstract

Background FKBP5 methylation levels are among the most studied epigenetic modifications related to psychiatric disorder vulnerability, however there are contradictory findings. We aimed to investigate the role of FKBP5 methylation in psychiatric disorders, in addition to its association with stress exposure (either life adversities, traumatic events or acute stress). Methods In accordance with PRISMA guidelines, ‘FKBP5’ and ‘methylation’ were searched in PubMed and Web of Science in March 2021. 330 studies were identified. Studies on non-psychiatric disorders, animal or cell lines were excluded. Type of study, sample size, sociodemographic properties of the participants, type of stress exposure, type of psychiatric disorder, CPG loci at FKBP5, and other related methods and covariates were extracted from 53 studies found to be eligible based on the inclusion criteria. Results Preliminary analysis showed that 19 studies investigated FKBP5 methylation in psychiatric disorders, 32 studies investigated the effects of stress types on FKBP5 methylation. Among the 197 CpG sites investigated, CpG at chr6:35,590,711 (intron 7), chr6:35,689,425 (promoter region), and chr6:35,590,736 (intron 7/GRE) sites were investigated by 26, 24, and 22 studies, respectively. CpG sites at chr6:35,590,736 and chr6:35,590,711 were reported to be linked to psychiatric disorder; CpG site at chr6:35,590,711, were reported to be linked to types of stress by more than half of the studies that investigated this region. Conclusions The studies on FKBP5 methylation and psychiatric disorder vulnerability are highly heterogeneous and most significant associations are found in intron 7. However, a great percentage of literature report insignificant associations of FKBP5 methylation sites with psychiatric disorder vulnerability.