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Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis

  • Xin Wang*
  • , Hong Xie
  • , Tian Chen
  • , Andrew S. Cotton
  • , Lauren E. Salminen
  • , Mark W. Logue
  • , Emily K. Clarke-Rubright
  • , John Wall
  • , Emily L. Dennis
  • , Brian M. O’Leary
  • , Chadi G. Abdallah
  • , Elpiniki Andrew
  • , Lee A. Baugh
  • , Jessica Bomyea
  • , Steven E. Bruce
  • , Richard Bryant
  • , Kyle Choi
  • , Judith K. Daniels
  • , Nicholas D. Davenport
  • , Richard J. Davidson
  • Michael DeBellis, Terri deRoon-Cassini, Seth G. Disner, Negar Fani, Kelene A. Fercho, Jacklynn Fitzgerald, Gina L. Forster, Jessie L. Frijling, Elbert Geuze, Hassaan Gomaa, Evan M. Gordon, Dan Grupe, Ilan Harpaz-Rotem, Courtney C. Haswell, Julia I. Herzog, David Hofmann, Michael Hollifield, Bobak Hosseini, Anna R. Hudson, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L. Kaufman, Anthony P. King, Saskia B. J. Koch, Inga K. Koerte, Mayuresh S. Korgaonkar, John H. Krystal, Christine Larson, Lauren A. M. Lebois, Ifat Levy, Gen Li, Vincent A. Magnotta, Antje Manthey, Geoffrey May, Katie A. McLaughlin, Sven C. Mueller, Laura Nawijn, Steven M. Nelson, Yuval Neria, Jack B. Nitschke, Miranda Olff, Elizabeth A. Olson, Matthew Peverill, K. Luan Phan, Faisal M. Rashid, Kerry Ressler, Isabelle M. Rosso, Kelly Sambrook, Christian Schmahl, Martha E. Shenton, Anika Sierk, Jeffrey S. Simons, Raluca M. Simons, Scott R. Sponheim, Murray B. Stein, Dan J. Stein, Jennifer S. Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Marijo Tamburrino, Sophia I. Thomopoulos, Nic J. A. van der Wee, Steven J. A. van der Werff, Theo G. M. van Erp, Sanne J. H. van Rooij, Mirjam van Zuiden, Tim Varkevisser, Dick J. Veltman, Robert R. J. M. Vermeiren, Henrik Walter, Li Wang, Ye Zhu, Xi Zhu, Paul M. Thompson, Rajendra A. Morey, Israel Liberzon
*Corresponding author for this work
  • University of Toledo
  • University of Southern California
  • Department of Veterans Affairs
  • Boston University
  • Duke University
  • VISN 6 MIRECC, Durham VA Health Care System, Durham, NC, USA
  • University of Utah
  • Yale University
  • University of Sydney
  • University of South Dakota
  • University of California at San Diego
  • University of Missouri at St. Louis
  • University of New South Wales
  • University of Groningen
  • University of Minnesota Twin Cities
  • University of Wisconsin-Madison
  • Medical College of Wisconsin
  • Emory University
  • Federal Aviation Administration
  • Marquette University
  • University of Otago
  • Amsterdam UMC - University of Amsterdam
  • University Medical Center Utrecht
  • Defense Healthcare Organization, Ministry of Defense, Utrecht, The Netherlands
  • Pennsylvania State University
  • Washington University St. Louis
  • Heidelberg University 
  • University of Münster
  • University of Illinois at Chicago
  • Ghent University
  • University of Cape Town
  • Wayne State University
  • Harvard University
  • University of Michigan, Ann Arbor
  • Radboud University Nijmegen
  • Ludwig Maximilian University of Munich
  • University of Wisconsin-Milwaukee
  • CAS - Institute of Psychology
  • University of Chinese Academy of Sciences
  • University of Iowa
  • Charité – Universitätsmedizin Berlin
  • VA Medical Center
  • University of Texas at Dallas
  • Baylor University
  • Texas A&M University
  • University of Deusto
  • Columbia University
  • Psychotrauma Research, Diemen, Netherlands
  • University of Washington
  • Ohio State University
  • Western University
  • University College London
  • Leiden University Medical Center
  • Leiden Institute for Brain and Cognition, Leiden, The Netherlands
  • University of California at Irvine
  • Youz-Parnassia Group, Leiden, The Netherlands
  • Department of Psychiatry
  • VU Vrije Universiteit
  • Ministry of Defense
  • Washington University School of Medicine
  • Harvard Medical School
  • Columbia University Medical Center
  • Arq National Trauma Center
  • University of Washington, Seattle
  • University California Irvine

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Abstract

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Original languageEnglish
Pages (from-to)4331-4343
Number of pages13
JournalMolecular psychiatry
Volume26
Issue number8
Early online date2020
DOIs
Publication statusPublished - Aug 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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