Longitudinal analyses of epigenetic pathways in deployed active duty Service Members

Abstract

BackgroundPre‐deployment identification of risk/ resilience factors is crucial in developing strategies to reduce or prevent post‐traumatic stress (PTSD) symptoms in military personnel. Management of PTSD is complicated because of the overlapping symptoms with the comorbid conditions and the diagnostic reliance on self‐report and time consuming psychological evaluation. A more comprehensive understanding of molecular pathophysiology of PTSD could facilitate an unbiased biomarker‐driven next‐generation intervention strategy. Herein, we study the epigenomic consequences of combat elicited PTSD in a longitudinal manner using blood methylation analysis.MethodsBlood samples were collected pre‐deployment, immediately post‐deployment, and at a three month follow‐up. This study assessed participants prior to stressor exposure during the index deployment and included comprehensive whole blood analysis. We collected self‐reports such as PTSD Checklist for DSM‐5 (PCL‐5) along with clinical tests. DNA methylation assays were carried out using Illumina 450K , followed by repeated‐measures ANOVA, correlation analysis, and PTSD differential analysis to characterize methylation status alterations associated with significant PTSD Check List (PCL) changes (PCL difference >10).ResultsWe identified 64 subjects with changes in PCL scores of 10 across the three phases of the sample collection. The correlation analysis between DNA methylation and the PCL5 trend identified genes from T cell pathways, dopamine receptor signaling and fatty acid activation pathways. We observed shifts in DNA methylation that distinguish PTSD from controls and also that tracks PTSD as measured by PCL5.ConclusionsWe observed shifts in DNA methylation related to deployment related adverse health outcomes. Active Duty cohort represented a real‐world scenario measured stress before and a short time after combat‐related trauma. Future work will integrate these epigenetic data with other molecular and clinical findings to better understand PTSD co‐morbidities, as well as susceptibility and resiliency.Support or Funding InformationResearch 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.