LAUSR

Background: Advances in the study of biological aging have identified that DNAmethylation data can be used to index cellular age and to evaluate pathogenic factors that accelerate aging. Stress, trauma, and posttraumatic stress disorder (PTSD) have been cross-sectionally associated with advanced DNA methylation age relative to chronological age, however longitudinal investigation is lacking. The aim of this study was to examine longitudinal associations between an array of posttraumatic psychiatric conditions and the pace of the epigenetic clock. Methods: 179 veterans (88% male, mean age 1⁄4 33 years) completed two assessments spanning approximately two years. Whole blood DNA methylation was interrogated via the Illumina EPIC beadchip and two indices of DNA methylation age quantified. Psychiatric diagnoses were assessed via structured interview. The pace of the epigenetic clock was operationalized as the difference between age estimates over time as a function of time between assessments. Results: In regressions, PTSD symptoms defined by avoidance of trauma-related cues and emotional numbing (p 1⁄4 .02) and alcohol-use disorders (p 1⁄4 .001) at time 1 were associated with an increasing pace of the epigenetic clock. Alcohol-use disorders were associated with 1.58 years in epigenetic age acceleration for every year between assessments. Conclusions: This is the first study to suggest that posttraumatic psychopathology is associated with a quickening pace of the epigenetic clock over time. This carries implications for understanding premature onset of age-related diseases among individuals with chronic psychopathology. It suggests that accelerated cellular aging may be a shared consequence across stress-related psychiatric symptoms. Supported By: US Dept of VA, CSR&D Merit Review Award Number I01 CX-001276-01; NIMH R21MH102834; NIMH 5T32MH019836-16