| Summary: | Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value = 3.75 × 10−34) and lower CD-RISC scores (P-value = 7.5 × 10−8) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value = 3.3 × 10−6), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value = 0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value = 0.023; r = 0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value = 0.02; r = 0.23). Post-hoc factor analyses revealed that this association was likely driven by “self-efficacy” items within the CD-RISC (P-value = 0.015; r = 0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost. Keywords: Epigenetic aging, Biomarkers, Veterans, Stress, PTSD, Resilience
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