Abstract
BackgroundPosttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD.MethodAdult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA‐PGC PTSD sites underwent T1‐weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel‐wise (brainageR) and region‐of‐interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site.ResultsBrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three‐way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages.DiscussionDifferential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age‐related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.
Highlights
Exposure to stress plays an important role in the development of medical conditions (Cohen & Manuck, 1995)
We examined the predictive ability of the brainageR, PHOTON-BA, and Brain-Age Regression Analysis and Computation Utility Software (BARACUS) machine learning pipelines to estimate brain age in a subsample of control subjects (n = 386) from three sites
We examined the relationship between age and Posttraumatic stress disorder (PTSD) diagnosis
Summary
Exposure to stress plays an important role in the development of medical conditions (Cohen & Manuck, 1995). Identification of accelerated aging processes may aid in detecting elevated risk for developing disease and provide opportunities for a personalized medicine approach to treatment. While peripheral biomarkers provide initial evidence for a link between PTSD and accelerated aging, identification of neural biomarkers is critical to understanding the complex relationships between PTSD, aging, and the brain. Given the known deleterious effects of aging on the brain (Schmitz et al, 2018), coupled with functional and structural brain changes associated with PTSD (Clausen et al, 2020; Logue et al, 2018; Morey et al, 2020), neural markers of accelerated aging in PTSD may help to stratify disease risk, clarify the pathology of psychiatric disease on the brain, and aid in the development of tailored treatments for PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan
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