Structural Covariance Networks in Post-Traumatic Stress Disorder: A Multisite ENIGMA-PGC Study
Authors: Rakesh Gopalkumar , Logue Mark , Clarke-Rubright Emily , O’Leary Brian M. , Haswell Courtney C. , Xie Hong , Thompson Paul M. , Dennis Emily L. , Jahanshad Neda , Koch Saskia B.J. , Frijling Jessie L. , Nawijn Laura , Olff Miranda , van Zuiden Mirjam , Rashid Faisal M. , Zhu Xi , De Bellis Michael D. , Daniels Judith K. , Sierk Anika , Manthey Antje , Stevens Jennifer S. , Jovanovic Tanja , Stein Murray B. , Shenton Martha , van de Werff Steven J.A. , van de Wee Nic J.A. , Vermeiren Robert R.J.M. , Schmahl Christian , Herzog Julia , Kaufman Milissa L. , O’Connor Lauren , Lebois Lauren A.M. , Baker Justin T. , Gruber Staci A. , Wolff Jonathan D. , Wolf Erika J. , Wintemitz Sherry R. , Gönenc Atilla , Ressler Kerry J. , Hofmann David Bernd , Bryant Richard A. , Korgaonkar Mayuresh , Andrew Elpiniki , Wang Li , Zhu Ye , Li Gen , Stein Dan J. , Ipser Jonathan , Koopowitz Sheri , Mueller Sven , Hudson Anna , Phan Luan , Hosseini Bobak , Angstadt K. Mike , King Anthony P. , Tamburrino Marijo , Skilliter Brynn C. , Geuze Elbert , van Rooij Sanne J.H. , Varkevisser Tim , McLaughlin Katie A. , Sheridan Margaret A. , Peverill Matthew , Sambrook Kelly , Veltman Dick J. , Thomaes Kathleen , Nelson Steven M. , May Geoffrey , Baugh Lee , Forster Gina , Simons Raluca , Simons Jeffrey , Magnotta Vincent , Fercho Kelene A , Maron-Katz Adi , du Plessis Stefan , Disner Seth , Davenport Nicholas , Thomopoulos Sophia I. , Suarez-Jimenez Benjamin , Wager Tor D. , Neria Yuval , Fani Negar , Walter Henrik , Koerte Inga , Bomyea Jessica , Choi Kyle , Simmons Alan N. , Olson Elizabeth , Rosso Isabelle , Straube Thomas , van Erp Theo G.M. , Chen Tian , Cotton Andrew S. , Wall John , Davidson Richard J. , deRoon-Cassini Terri , Fitzgerald Jacklynn , Larson Christine , Gordon Evan , Grupe Dan , Sponheim Scott R. , Etkin Amit , Seedat Soraya , Harpaz-Rotem Ilan , Wrocklage Kristen , Abdallah Chadi G. , Krystal John H. , Levy Ifat , Gomaa Hassaan , McMahon Mary Agnes B. , Liberzon Israel , Wang Xin , Sun Delin , Morey Rajendra A. 
Published: March 2021

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 subjects’ data from 29 cohorts in five countries (n=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 (≤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 a node’s 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.