Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium

Raluca M. Simons, Jeffrey S. Simons, Vincent A. Magnotta, Adi Maron-Katz, Stefan du Plessis, Seth G. Disner, Nicholas D. Davenport, Dan Grupe, Jack B. Nitschke, Terri A. deRoon-Cassini, Jacklynn Fitzgerald, John H. Krystal, Ifat Levy, Miranda Olff, Li Wang, Yuval Neria, Michael D. de Bellis, Tanja Jovanovic, Judith K. Daniels, Martha E. ShentonNic J. A. van de Wee, Christian Schmahl, Milissa L. Kaufman, Isabelle M. Rosso, Scott R. Sponheim, David Bernd Hofmann, Richard A. Bryant, Kelene A. Fercho, Dan J. Stein, Sven C. Mueller, K. Luan Phan, Katie A. McLaughlin, Richard J. Davidson, Christine Larson, Geoffrey May, Steven M. Nelson, Chadi G. Abdallah, Hassaan Gomaa, Amit Etkin, Soraya Seedat, Ilan Harpaz-Rotem, Israel Liberzon, Xin Wang, Paul M. Thompson, Rajendra A. Morey, ENIGMA Consortium PGC-PTSD

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Background: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). Methods: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2–85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis–Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2–148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks. Results: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks. Conclusions: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD.

Original languageEnglish
Pages (from-to)935-948
Number of pages14
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number9
Early online date2022
Publication statusPublished - Sept 2022


  • Brain network
  • Cortical thickness
  • Depression
  • PTSD
  • Structural covariance
  • Surface area

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