Post-Traumatic Stress Disorder and Risk of Degenerative Synucleinopathies: Systematic Review and Meta-Analysis

Abstract

A systematic review was conducted to answer whether adult-onset post-traumatic stress disorder (PTSD) is associated with increased risk of Parkinson's disease (PD) and related synucleinopathies. A systematic search of Medline (Ovid), Embase (Elsevier), PsycInfo (Ovid), Cochrane Library (Wiley), and Web of Science (Clarivate) was performed using MeSH headings and equivalent terms for PTSD, PD, DLB, and related disorders. No restrictions. Eligible articles were published in peer-reviewed journals, sampled adult human populations, and treated PTSD and degenerative synucleinopathies as exposures and outcomes, respectively. Extracted data included diagnostic methods, sample characteristics, matching procedures, covariates, and effect estimates. Bias assessment was performed with the Newcastle-Ottawa scale. Hazard ratios were pooled using the random effects model, and the Hartung-Knapp adjustment was applied due to the small number of studies. A total of six articles comprising seven unique samples (total n=1,747,378) met eligibility criteria. The risk of PD was reported in three retrospective cohort studies and one case-control study. Risk of DLB was reported in one retrospective cohort, one case-control, and one prospective cohort study. No studies addressed potential relationships with multiple system atrophy or pure autonomic failure. Meta-analysis of hazard ratios from four retrospective cohort studies supported the hypothesis that incident PTSD was associated with PD and DLB risk (pooled HR 1.88, 95% C.I. 1.08-3.24; p=0.035). The sparse literature to-date supports further investigations on the association of mid- to late-life PTSD with Parkinson's and related neurodegenerative disorders.