Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on

Abstract

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.

A Systematic Review of DNA Methylation and Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic Growth, and Resilience

“…Van Zuiden and colleagues () successfully created a diagnostic classifier containing three pretrauma variables: high GR numbers, high GILZ expression, and low FKBP5 expression. All of these findings are interesting in the context of a recent cross‐sectional study in which it was shown that gene expression changes observed cross‐sectionally in veterans (i.e., after trauma exposure) overlapped significantly with those observed before and after combat exposure in two independent replication samples, highlighting that these gene expression changes were modified postcombat (Mehta, Voisey, et al., ).…”

A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age

“…Childhood trauma was examined in four studies, but only one of these reported a significant association with childhood sexual abuse (40), that was supported by the findings of the meta-analysis of three studies (33). Six studies investigated lifetime posttraumatic stress disorder in predominantly war veterans (33,49,61,(69)(70)(71). Four of these reported no association overall.…”

“…A number of studies combined data from multiple cohorts (27,32), including one meta-analysis (33). Even when excluding the meta-analysis (33), multiple cohorts were used in more than one study; Women's Health Initiative (WHI) Study (27,32,(34)(35)(36), Lothian Birth Cohort 1936 (LBC1936) (37-39), Medical Research Council (MRC) National Survey of Health & Development (NSHD) (32,40,41), The Parkinson's disease, Environment & Genes (PEG) study (27,32,42), Veterans Affairs Normative Aging Study (43,44), Adults in the Making Project (AIM) (45,46), Strong African American Healthy Adult Project (SHAPE) (45)(46)(47)(48), Grady Trauma Project (GTP) (49,50), Family and Community Health Study (FACHS) (30,51), Invecchiare nel Chianti (INC) (32,36), and the Epidemiological Investigations of the Changes of Preventing, Recognizing Early and Optimally Treating Chronic Diseases in an Elderly Population (ESTHER) cohort (52,53).…”

“…The tenth study was a meta-analysis that brought together nine cohorts (33), some of which already featured in other studies shown in the table, for example, PRISMO (69) and TRACTS (70). The Grady Trauma Project (GTP) cohort was used in two of the studies (49,50), although it is unclear if the sample participants were included in both. Childhood trauma was examined in four studies, but only one of these reported a significant association with childhood sexual abuse (40), that was supported by the findings of the meta-analysis of three studies (33).…”

In Search for Biomarkers, Endophenotypes or Biosignatures of Ptsd: What Have We Learned From the South East European Study

“…Although understanding resilience is very important for understanding, preventing and treating PTSD (see Horn & Feder 2018) resilience as a research aim (see Mehta et al 2018) and treatment target has been largely neglected. Resilience does not mean just the absence of PTSD.…”