Work

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

Year: 2026

Type: article

Study design: Observational Study

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.

Source: Carolina Digital Repository (University of North Carolina at Chapel Hill)

DOI: 10.17615/ahca-qp98

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

Institution: University of North Carolina at Chapel Hill

Topic: Posttraumatic Stress Disorder Research

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Veterans Affairs, Michael J. Fox Foundation for Parkinson's Research, Bill and Melinda Gates Foundation, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Yale University, Biogen, Office of Research and Development, Waisman Center, Sunovion, National Alliance for Research on Schizophrenia and Depression, Sage Therapeutics, Georgia Clinical and Translational Science Alliance, FORUM Pharmaceuticals, Otsuka America, Traumatic Brain Injury Center of Excellence, National Research Foundation, South African Medical Research Council, Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, ZonMw, Chinese Academy of Sciences, Astellas Pharma, H. Lundbeck A/S, Canadian Institute for Military and Veteran Health Research, National Institutes of Health, Institute for Clinical and Translational Research, University of Wisconsin, Madison, Novartis Pharma, Clinical Science Research and Development, National Center for PTSD, U.S. Department of Veterans Affairs, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, Division of Research Capacity Development, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Yale Center for Clinical Investigation, Yale School of Medicine, Congressionally Directed Medical Research Programs, Medical Research and Materiel Command

Awards: Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder, G1123890210, G1259492744, G1334251766, G1453759871, G1650819308, Laboratory of Neuro Imaging Resource (LONIR), G1786539460, G1807714095, G217254845, Neurobiology of Traumatic Dissociation in a Transdiagnostic Study of Women with Childhood Maltreatment, G2224401916, G2255279329, G2284422223, G2471646051, G2531818126, G2831939486, G296453017, G3228647855, G3369081490, G3504454571, G3647294381, G3735175714, G3804724313, G4119534169, G425672610, G4336321580, G4475667458, G4909918869, NEURAL AND BEHAVIORAL CORRELATES OF PTSD AND ALCOHOL USE, Longitudinal Tracking of Traumatic Brain Injury: Advanced Connectomics, G5142766902, G528601746, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5640978069, G5834923403, G5850682332, G596576537, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G6173816828, G6253227394, G6587689818, G661928818, G6792506723, Solar-Eclipse Computational Tools for Imaging Genetics, Translating Science into Better Posttraumatic Mental Health, G7394953146, G764699806, G7794516033, G7923909899, High resolution mapping of the genetic risk for disease in the aging brain, G8151151163, PTSD/TBI CLINICAL CONSORTIUM COORDINATING CENTER AND CLINICAL SITE AWARD, A global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA Consortium, G8632625050, G8836174225, G8957659042, G8971597848, G9000000297, G9000029981, G9000060093, G9000060504, G9000071967, G9000076959, G9000087036, G9000116029, G9000129531, G9000159916, G9000162060, G9000249275, G9000250461, G9000278947, G9000304527, G9000311428, The Effects of Explosive Blast as Compared to Post-Traumatic Stress Disorder on Brain Function and Structure, G961545024, G9987375

OpenAlex ID: W7141383134

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