Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD symptoms and PTSD Symptom Profiles in Military Personnel

Abstract

In military personnel, post‐traumatic stress disorder (PTSD) occurs and is associated with differential DNA methylation. But, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD SYMPTOMATOLOGY are not understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms, and IF DNA methylation changes ARE related to an increase in PTSD severity. Symptom measures were obtained and methylated DNA was measured from peripheral blood mononuclear cells (PBMC) at baseline and 3 months later. All measures were compared between subjects with PTSD (n=8) and combat matched controls without PTSD (n=6) at follow‐up. Additionally, changes in DNA methylation in military personnel with clinically relevant increases in PTSD symptoms were determined and compared to controls with no clinical changes in PTSD. Compared to controls at follow‐up, military personnel with PTSD had 10 genes that were significantly hypermethylated and 18 that were significantly hypomethylated, including USP17, SDHAP3, and HISTH4C. In military personnel with clinically elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation, and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD onset group relate to the canonical pathways of netrin signaling, Wnt/Ca+ pathway, and axonal guidance signaling. These gene‐pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.