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

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

Posted 20 Jun 2019
bioRxiv DOI: 10.1101/677153

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 (Cohens 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.

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