Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium

Abstract

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed, which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3,049 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1,446 individuals with PTSD and 1,603 controls (2152 males/897 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d=-0.12, p=0.0021). The tapetum connects the left and right hippocampus, structures for which structure and function have been consistently implicated in PTSD. Results remained significant/similar after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

The ENIGMA Brain Injury working group: approach, challenges, and potential benefits

“…One group that has been successful in receiving grant support is the Post-Traumatic Stress Disorder (PTSD) working group. The PTSD working group has considerable overlap in membership with the Military Brain Injury subgroup and has also published papers on subcortical volume (Logue et al 2017) and white matter microstructure (Dennis et al 2019). The ENIGMA Addiction working group has similarly received grant support, and recently published a paper of 3,240 individuals examining multiple substances.…”

The dissociative subtype of posttraumatic stress disorder is associated with subcortical white matter network alterations

“…It thus remains unclear whether the observed symptomatology is further underpinned by structural alterations of the white matter in PTSD-D. Various studies have reported white matter alterations in PTSD (Daniels et al 2013;Dennis et al 2019;Siehl et al 2018). Yet, to our knowledge, no study to date has differentiated between the subtypes while againonly local aberrations have been investigated for the exception of one recent study, which reported differences in white matter network organization in PTSD compared to trauma-exposed controls (Suo et al 2019).…”