Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium
Authors: Dennis Emily L , Disner Seth G , Fani Negar , Salminen Lauren E , Logue Mark , Clarke Emily K , Haswell Courtney C , Averill Christopher L , Baugh Lee A , Bomyea Jessica , Bruce Steven E , Cha Jiook , Choi Kyle , Davenport Nicholas D , Densmore Maria , du Plessis Stefan , Forster Gina L , Frijling Jessie L , Gönenc Atilla , Gruber Staci , Grupe Daniel W , Guenette Jeffrey P , Hayes Jasmeet , Hofmann David , Ipser Jonathan , Jovanovic Tanja , Kelly Sinead , Kennis Mitzy , Kinzel Philipp , Koch Saskia BJ , Koerte Inga , Koopowitz Sheri , Korgaonkar Mayuresh , Krystal John , Lebois Lauren AM , Li Gen , Magnotta Vincent A , Manthey Antje , May Geoffrey J , Menefee Deleene S , Nawijn Laura , Nelson Steven M , Neufeld Richard WJ , Nitschke Jack B , O’Doherty Daniel , Peverill Matthew , Ressler Kerry , Roos Annerine , Sheridan Margaret A , Sierk Anika , Simmons Alan , Simons Raluca M , Simons Jeffrey S , Stevens Jennifer , Suarez-Jimenez Benjamin , Sullivan Danielle R , Théberge Jean , Tran Jana K , van den Heuvel Leigh , van der Werff Steven JA , van Rooij Sanne JH , van Zuiden Mirjam , Velez Carmen , Verfaellie Mieke , Vermeiren Robert RJM , Wade Benjamin SC , Wager Tor , Walter Henrik , Winternitz Sherry , Wolff Jonathan , York Gerald , Zhu Ye , Zhu Xi , Abdallah Chadi G , Bryant Richard , Daniels Judith K , Davidson Richard J , Fercho Kelene A , Franz Carol , Geuze Elbert , Gordon Evan M , Kaufman Milissa L , Kremen William , Lagopoulos Jim , Lanius Ruth A , Lyons Michael J , McCauley Stephen R , McGlinchey Regina , McLaughlin Katie A , Milberg William , Neria Yuval , Olff Miranda , Seedat Soraya , Shenton Martha , Sponheim Scott R , Stein Dan J , Stein Murray B , Straube Thomas , Tate David F , van der Wee Nic JA , Veltman Dick J , Wang Li , Wilde Elisabeth A , Thompson Paul M , Kochunov Peter , Jahanshad Neda , Morey Rajendra A 
Published: June 2019

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’sd=−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.