Longitudinal changes in glucocorticoid receptor exon 1 methylation and psychopathology after military deployment.

Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1 region (GR-1) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1 methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1 methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1 methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1 expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1 methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1 methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.