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Structural Covariance Networks in Post-Traumatic Stress Disorder: A Multisite ENIGMA-PGC Study

By Gopalkumar Rakesh, Delin Sun, Mark W. Logue, Emily Clarke-Rubright, Brian M. O'Leary, Courtney C. Haswell, Hong Xie, Paul Thompson, Emily Dennis, Neda Jahanshad, Saskia Koch, Jessie Frijling, Laura Nawijn, Miranda Olff, Mirjam van Zuiden, Faisal Rashid, Xi Zhu, Michael De Bellis, Judith K Daniels, Anika Sierk, Antje Manthey, Jennifer S Stevens, Tanja Jovanovic, Murray Stein, Martha Shenton, Steven JA van der Werff, Nic JA van der Wee, Robert RJM Vermeiren, Christian Schmahl, Julia I. Herzog, Milissa L Kaufman, Lauren O'Connor, Lauren A.M Lebois, Justin T. Baker, Staci A Gruber, Jonathan D Wolff, Erika J Wolf, Sherry Winternitz, Atilla Gonenc, Kerry J Ressler, David Hofmann, Richard A Bryant, Mayuresh Korgaonkar, Elpiniki Andrew, Li Wang, Ye Zhu, Gen LI, Dan J. Stein, Jonathan Ipser, Sheri Koopowitz, Sven C. Mueller, Anna Hudson, Luan Phan, Bobak Hosseini, K. Mike Angstadt, Anthony King, Marijo Tamburrino, Brynn P. Skilliter, Elbert Geuze, Sanne J.H. van Rooij, Tim Varkevisser, Katie A. McLaughlin, Margaret A. Sheridan, Matthew Peverill, Kelly Sambrook, Dick J. Veltman, Kathleen Thomaes, Steven Nelson, Geoffrey May, Lee Baugh, Gina Forster, Raluca Simons, Jeffrey Simons, Vincent Magnotta, Kelene A. Fercho, Adi Maron-Katz, Stefan du Plessis, Seth Disner, Nicholas Davenport, Sophia I Thomopoulos, Benjamin Suarez-Jimenez, Tor D. Wager, Yuval Neria, Negar Fani, Henrik Walter, Inga Koerte, Jessica Bomyea, Kyle Choi, Alan N. Simmons, Elizabeth Olson, Isabelle Rosso, Thomas Straube, Theo GM Van Erp, Tian Chen, Andrew S. Cotton, John Wall, Richard J. Davidson, Terri deRoon-Cassini, Jacklynn Fitzgerald, Christine Larson, Evan Gordon, Dan Grupe, Scott R. Sponheim, Amit Etkin, Soraya Seedat, Ilan Harpaz-Rotem, Kristen Wrocklage, Chadi G. Abdallah, John H. Krystal, Ifat Levy, Hassaan Gomaa, Mary Agnes B. McMahon, Israel Liberzon, Xin Wang, Rajendra A. Morey

Posted 16 Mar 2021
bioRxiv DOI: 10.1101/2021.03.13.432212

Introduction - Cortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subject data from 29 cohorts in five countries (3439). Methods - Using Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN. Results - Notable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus. Conclusion - Unlike previous studies with smaller sample sizes (less than 318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into nodal relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

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