Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

• Type of Material: Article
• Authors: Emily L. Dennis, Brigham and Women's Hospital; Seth G. Disner, VA Midwest Health Care Network; Negar Fani, Emory University; Laure E. Salminen, Keck School of Medicine; Mark Logue, VA Boston Healthcare System; Emily K. Clarke, Duke University; Courtney C. Haswell, Duke University; Tanja Jovanovic, Emory University; Kerry Ressler, Emory University; Jennifer Stevens, Emory University; Sanne van Rooij, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: Nature
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019, The Author(s), under exclusive licence to Springer Nature Limited
• Final Published Version (URL): http://dx.doi.org/10.1038/s41380-019-0631-x
• Title of Journal or Parent Work: Molecular Psychiatry
• Keywords: altered structural connectivity; posttraumatic stress disorder; neurobiological vulnerability; alterations in white matter organization; diffusion MRI; PGC-ENIGMA PTSD working group
• Research Categories: Biology, Neuroscience; Psychology, Cognitive

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 3047 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 1426 individuals with PTSD and 1621 controls (2174 males/873 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 = −0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even 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.