DNA methylation correlates of PTSD: Recent findings and technical challenges

There is increasing evidence that epigenetic factors play a critical role in posttraumatic stress disorder (PTSD), by mediating the impact of environmental exposures to trauma on the regulation of gene expression. DNA methylation is one epigenetic process that has been highly studied in PTSD. This review will begin by providing an overview of DNA methylation (DNAm) methods, and will then highlight two major biological systems that have been identified in the epigenetic regulation in PTSD: (a) the immune system and (b) the stress response system. In addition to candidate gene approaches, we will review novel strategies to study epigenome-wide PTSD-related effects, including epigenome-wide algorithms that distill information from many loci into a single summary score (e.g., measures of "epigenetic age" which have been associated with PTSD). This review will also cover recent epigenome wide association studies (EWAS) of PTSD, and biological pathway models used to identify gene sets enriched in PTSD. Finally, we address technical and methodological advances and challenges to the field, and highlight exciting directions for future research.