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

• Type of Material: Article
• Authors: Delin Sun, Duke University; Gopalkumar Rakesh, Duke University; Emily K. Clarke-Rubright, Duke University; Courtney C. Haswell, Duke University; Mark Logue, Boston University; Jennifer S. Stevens, Emory University; Negar Fani, Emory University; Sanne van Rooij, Emory University; Kerry Ressler, Emory University; Tanja Jovanovic, Emory University; Rajendra A. Morey, Duke University
• Language: English
• Date: 2022-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.bpsc.2022.02.008
• Title of Journal or Parent Work: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
• Volume: 7
• Issue: 9
• Start Page: 935
• End Page: 948
• Grant/Funding Information: DoD W81XWH-10-1-0925; Center for Brain and Behavior Research Pilot Grant; South Dakota Governor’s Research Center Grant; CX001600 VA CDA; NHMRC Program Grant #1073041; R01 MH111671; VISN6 MIRECC; German Research Foundation grant to J. K. Daniels (DA 1222/4-1 and WA 1539/8-2); VA RR&D 1IK2RX000709; NIMH R01-MH043454; NIMH T32-MH018931; 5U01AA021681-08; K24MH71434; K24 DA028773; R01 MH63407; R01 AA12479; R01 MH61744; K99NS096116; VA RR&D 1K1RX002325; VA RR&D 1K2RX002922; MH101380; ZonMw, the Netherlands organization for Health Research and Development grant to Miranda Olff (40-00812-98-10041); Academic Medical Center Research Council grant to Miranda Olff (110614); VA CSR&D 1IK2CX001680; VISN17 Center of Excellence pilot funding; NIMH R01MH105535; NIMH 1R21MH102634; German Federal Ministry of Education and Research (BMBF RELEASE 01KR1303A); German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07); R01MH111671; R01MH117601; R01AG059874; MJFF 14848; MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850; R21MH112956; Anonymous Women’s Health Fund; Kasparian Fund; Trauma Scholars Fund; Barlow Family Fund; W81XWH-08-2-0159; Department of Veterans Affairs via support for the National Center for PTSD; NIAAA via its support for (P50) Center for the Translational Neuroscience of Alcohol; NCATS via its support of (CTSA) Yale Center for Clinical Investigation; NIH R01 MH106574; F32MH109274; NIMH 1R21MH102634; R01MH113574; R01-MH103291; BOF 2-4 year project to Sven C. Mueller (01J05415); R01MH105355; Dana Foundation (to Dr. Nitschke); the University of Wisconsin Institute for Clinical and Translational Research; a National Science Foundation Graduate Research Fellowship (to Dr. Grupe); the National Institute of Mental Health (NIMH) R01 MH63407 (to De Bellis), R01 AA12479 (to De Bellis), and R01 MH61744 (to De Bellis); R01-MH043454 and T32-MH018931 (to Dr. Davidson); core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30-HD003352); NIMH K23MH112873; Veterans Affairs Merit Review Program (10/01/08 - 09/30/13); L30 MH114379; German Federal Ministry of Education and Research (BMBF RELEASE 01KR1303A); South African Medical Research Council “SHARED ROOTS” Flagship Project; Grant MRC-RFA-FSP-01-2013/SHARED ROOTS; South African Research Chair in PTSD from the Department of Science and Technology and the National Research Foundation; US Department of Defence Grant W81XWH08-2-0159 (PI: Stein, Murray B); VA RR&D I01RX000622; CDMRP W81XWH-08-2-0038; South African Medical Research Council; NARSAD Young Investigator; K01 MH118428; Department of Defense award number W81XWH-12-2-0012; ENIGMA was also supported in part by NIH U54 EB020403 from the Big Data to Knowledge (BD2K) program; R56AG058854; R01MH116147; R01MH111671; P41 EB015922; 1R01MH110483; 1R21 MH098198; R01MH105355-01A.
• Keywords: PTSD; Depression; Brain Network; Cortical Thickness; Structural Covariance; Surface Area
• Research Categories: Biology, Neuroscience; Psychology, Behavioral; Psychology, Cognitive

Abstract

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 between-group differences in 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. For methodologic confirmation we demonstrated that PTSD patients had higher mean SC as compared to random networks in CT-based and SA-based atrophic networks, CT-based and SA-based hypertrophic networks, and CT-based stable networks. We also confirmed that non-PTSD participants showed higher mean SC than random networks in CT-based and SA-based atrophic networks, and SA-based hypertrophic networks. Results: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Patients with PTSD alone showed lower mean SC in CT-based atrophic networks than patients with depression alone, and higher mean SC in SA-based atrophic networks than PTSD patients with comorbid depression as well as healthy controls. 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.