Evaluating the impact of trauma and PTSD on epigenetic prediction of lifespan and neural integrity

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in some people following trauma exposure. Trauma and PTSD have been associated with accelerated cellular aging. This study evaluated the effect of trauma and PTSD on accelerated GrimAge, an epigenetic predictor of lifespan, in traumatized civilians. This study included 218 individuals with current PTSD, 427 trauma-exposed controls without any history of PTSD and 209 subjects with lifetime PTSD history who are not categorized as current PTSD cases. The Traumatic Events Inventory (TEI) and Clinician-Administered PTSD Scale (CAPS) were used to measure lifetime trauma burden and PTSD, respectively. DNA from whole blood was interrogated using the MethylationEPIC or HumanMethylation450 BeadChips. GrimAge estimates were calculated using the methylation age calculator. Cortical thickness of 69 female subjects was assessed by using T1-weighted structural MRI images. Associations between trauma exposure, PTSD, cortical thickness, and GrimAge acceleration were tested with multiple regression models. Lifetime trauma burden (p = 0.03), current PTSD (p = 0.02) and lifetime PTSD (p = 0.005) were associated with GrimAge acceleration, indicative of a shorter predicted lifespan. The association with lifetime PTSD was replicated in an independent cohort (p = 0.04). In the MRI sub sample, GrimAge acceleration also associated with cortical atrophy in the right lateral orbitofrontal cortex (p_adj = 0.03) and right posterior cingulate (p_adj = 0.04), brain areas associated with emotion-regulation and threat-regulation. Our findings suggest that lifetime trauma and PTSD may contribute to a higher epigenetic-based mortality risk. We also demonstrate a relationship between cortical atrophy in PTSD-relevant brain regions and shorter predicted lifespan.

Fig. 1. Associations between GrimAge acceleration and (a) Lifetime trauma and (b) PTSD.

a Lifetime trauma is assessed by Traumatic Events Inventory (TEI) score. Red line shows linear best fit for the multiple regression model that includes CD8T, CD4T, NK, B cell, mono, sex and array type as covariates. Blue shaded area represents 95% confidence region. b Results are p values from Wilcoxon test for post hoc pairwise comparisons.

Fig. 2. Associations between GrimAge acceleration and (a) Right lateral orbitofrontal cortex and (b) Right posterior cingulate cortex thickness.

a Red line shows linear best fit for the multiple regression model that includes right lateral orbitofrontal thickness as dependent variable, GrimAge as predictor and age as a covariate. Blue shaded area represents 95% confidence region. b Red line shows linear best fit for the multiple regression model that includes right posterior cingulate thickness as dependent variable, GrimAge as predictor and age as a covariate. Blue shaded area represents 95% confidence region.