Dataset Information

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 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 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.

SUBMITTER: Dennis EL

PROVIDER: S-EPMC7302988 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Dennis Emily L EL Disner Seth G SG Fani Negar N Salminen Lauren E LE Logue Mark M Clarke Emily K EK Haswell Courtney C CC Averill Christopher L CL Baugh Lee A LA Bomyea Jessica J Bruce Steven E SE Cha Jiook J Choi Kyle K Davenport Nicholas D ND Densmore Maria M du Plessis Stefan S Forster Gina L GL Frijling Jessie L JL Gonenc Atilla A Gruber Staci S Grupe Daniel W DW Guenette Jeffrey P JP Hayes Jasmeet J Hofmann David D Ipser Jonathan J Jovanovic Tanja T Kelly Sinead S Kennis Mitzy M Kinzel Philipp P Koch Saskia B J SBJ Koerte Inga I Koopowitz Sheri S Korgaonkar Mayuresh M Krystal John J Lebois Lauren A M LAM Li Gen G Magnotta Vincent A VA Manthey Antje A May Geoff J GJ Menefee Deleene S DS Nawijn Laura L Nelson Steven M SM Neufeld Richard W J RWJ Nitschke Jack B JB O'Doherty Daniel D Peverill Matthew M Ressler Kerry J KJ Roos Annerine A Sheridan Margaret A MA Sierk Anika A Simmons Alan A Simons Raluca M RM Simons Jeffrey S JS Stevens Jennifer J Suarez-Jimenez Benjamin B Sullivan Danielle R DR Théberge Jean J Tran Jana K JK van den Heuvel Leigh L van der Werff Steven J A SJA van Rooij Sanne J H SJH van Zuiden Mirjam M Velez Carmen C Verfaellie Mieke M Vermeiren Robert R J M RRJM Wade Benjamin S C BSC Wager Tor T Walter Henrik H Winternitz Sherry S Wolff Jonathan J York Gerald G Zhu Ye Y Zhu Xi X Abdallah Chadi G CG Bryant Richard R Daniels Judith K JK Davidson Richard J RJ Fercho Kelene A KA Franz Carol C Geuze Elbert E Gordon Evan M EM Kaufman Milissa L ML Kremen William S WS Lagopoulos Jim J Lanius Ruth A RA Lyons Michael J MJ McCauley Stephen R SR McGlinchey Regina R McLaughlin Katie A KA Milberg William W Neria Yuval Y Olff Miranda M Seedat Soraya S Shenton Martha M Sponheim Scott R SR Stein Dan J DJ Stein Murray B MB Straube Thomas T Tate David F DF van der Wee Nic J A NJA Veltman Dick J DJ Wang Li L Wilde Elisabeth A EA Thompson Paul M PM Kochunov Peter P Jahanshad Neda N Morey Rajendra A RA

Molecular psychiatry 20191219 8

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 coho ...[more]

PMID: 31857689

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Project description:BackgroundRecent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.MethodsWe analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.ResultsWe found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance.ConclusionThese results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Dataset Information

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

Publications

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

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