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

Delin Sun, Gopalkumar Rakesh, Emily K Clarke-Rubright, Courtney C Haswell, Mark Logue, Erin N O'Leary, Andrew S Cotton, Hong Xie, Emily L Dennis, Neda Jahanshad, Lauren E Salminen, Sophia I Thomopoulos, Faisal Rashid, Christopher R K Ching, Saskia B J Koch, Jessie L Frijling, Laura Nawijn, Mirjam van Zuiden, Xi Zhu, Benjamin Suarez-JimenezAnika Sierk, Henrik Walter, Antje Manthey, Jennifer S Stevens, Negar Fani, Sanne J H van Rooij, Murray Stein, Jessica Bomyea, Inga Koerte, Kyle Choi, Steven J A van de Werff, Robert R J M Vermeiren, Julia Herzog, Lauren A M Lebois, Justin T Baker, Kerry J Ressler, Elizabeth A Olson, Thomas Straube, Mayuresh S Korgaonkar, Elpiniki Andrew, Ye Zhu, Gen Li, Jonathan Ipser, Anna Hudson, Matthew Peverill, Kelly Sambrook, Evan Gordon, Lee Baugh, Gina Forster, Raluca Simons, Jeffrey Simons, Vincent Magnotta, Adi Maron-Katz, Stefan du Plessis, Seth Disner, Nicholas Davenport, Dan Grupe, Jack Nitschke, Terri A deRoon-Cassini, Jacklynn Fitzgerald, John H Krystal, Ifat Levy, Miranda Olff, Dick J Veltman, Li Wang, Yuval Neria, Michael D De Bellis, Tanja Jovanovic, Judith K Daniels, Martha Shenton, Nic 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, 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 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 to the mean SC of 5,000 randomly generated n-region networks.

RESULTS: Patients with PTSD, relative to non-PTSD controls, 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 structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted 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 date15-Mar-2022
Publication statusPublished - Sep-2022

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