Longitudinal Analysis of DNA Methylation Status Linked to Post‐Traumatic Stress Disorder in Deployed Service Members

Abstract

Pre‐deployment identification of risk and resilience factors is crucial in developing strategies to reduce or prevent post‐traumatic stress (PTSD) symptoms in military personnel. Combat and deployment itself can result in drastic changes in activity, diet, and stress, often with detectable molecular consequences. This longitudinal study was designed to assess the effects of deployment on DNA methylation in peripheral blood. Blood samples were collected pre‐deployment, immediately post‐deployment, and at a three month follow‐up. A battery of clinical tests and self‐reported psychological data were included in the study. DNA methylation assays, followed by repeated‐measures ANOVA, correlation analysis, and PTSD differential analysis were carried out to characterize methylation status alterations associated with significant PTSD Check List (PCL) changes (PCL difference >10). We identified 64 subjects with increases in PCL scores of 10 across the three phases of the sample collection. Repeated‐measures ANOVA testing, adjusted for cell composition and age, was conducted on 2415 methylation probes. 72 significantly differentially methylated probes were identified that were associated with Netrin, mTOR, hypoxia, and ubiquitination pathways. Correlation and differential analysis between PTSD and control samples identified 51 genes passing mean p‐value cutoffs across analyses. These genes are involved in the cAMP, mTOR, opioid, and CREB signaling pathways. Our findings will contribute to understanding the pathogenesis of PTSD co‐morbid conditions and provide mechanistic insights which may aid in averting the onset of chronic PTSD. Future work will integrate these epigenetic data with other molecular ‐omics and clinical findings to better understand PTSD co‐morbidities, as well as susceptibility and resiliency.Disclaimers:Research was conducted in compliance with all Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.Support or Funding InformationThis study was supported by USAMRMC grant No: 09284002.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.