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

doi:10.1038/s41380-020-00967-1

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

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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, …

Molecular psychiatry, Vol.26(8), pp.4331-4343

12/07/2020

DOI: 10.1038/s41380-020-00967-1

PMCID: PMC8180531

PMID: 33288872

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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.

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Title: Subtitle: Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis
Creators: Xin Wang - Department of Psychiatry, University of Toledo, Toledo, OH, USA. xin.wang2@utoledo.edu
Hong Xie - Department of Neurosciences, University of Toledo, Toledo, OH, USA
Tian Chen - Department of Mathematics and Statistics, University of Toledo, Toledo, OH, USA
Andrew S Cotton - Department of Psychiatry, University of Toledo, Toledo, OH, USA
Lauren E Salminen - Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Mark W Logue - Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
Emily K Clarke-Rubright - VISN 6 MIRECC, Durham VA Health Care System, Durham, NC, USA
John Wall - Department of Neurosciences, University of Toledo, Toledo, OH, USA
Emily L Dennis - Department of Neurology, University of Utah, Salt Lake City, UT, USA
Brian M O'Leary - Department of Psychiatry, University of Toledo, Toledo, OH, USA
Chadi G Abdallah - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Elpiniki Andrew - University of Sydney, Westmead, NSW, Australia
Lee A Baugh - Sioux Falls VA Health Care System, Sioux Falls, SD, USA
Jessica Bomyea - Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
Steven E Bruce - Center for Trauma Recovery, Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, USA
Richard Bryant - School of Psychology, University of New South Wales, Sydney, NSW, Australia
Kyle Choi - Health Services Research Center, University of California, San Diego, La Jolla, CA, USA
Judith K Daniels - Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands
Nicholas D Davenport - Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
Richard J Davidson - Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
Michael DeBellis - Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
Terri deRoon-Cassini - Department of Surgery, Division of Trauma & Acute Care Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
Seth G Disner - Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
Negar Fani - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Kelene A Fercho - Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA
Jacklynn Fitzgerald - Department of Psychology, Marquette University, Milwaukee, WI, USA
Gina L Forster - Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
Jessie L Frijling - Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands
Elbert Geuze - Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
Hassaan Gomaa - Department of Psychiatry and Behavioral Health, Penn State College of Medicine, Hershey, PA, USA
Evan M Gordon - Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Dan Grupe - Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
Ilan Harpaz-Rotem - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Courtney C Haswell - VISN 6 MIRECC, Durham VA Health Care System, Durham, NC, USA
Julia I Herzog - Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
David Hofmann - Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
Michael Hollifield - Program for Traumatic Stress, Tibor Rubin VA Medical Center, Long Beach, CA, USA
Bobak Hosseini - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
Anna R Hudson - Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium
Jonathan Ipser - Department of Psychiatry, University of Cape Town, Cape Town, South Africa
Neda Jahanshad - Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Tanja Jovanovic - Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA
Milissa L Kaufman - Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Anthony P King - Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
Saskia B J Koch - Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
Inga K Koerte - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
Mayuresh S Korgaonkar - Brain Dynamics Centre, Westmead Institute of Medical Research, University of Sydney, Westmead, NSW, Australia
John H Krystal - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Christine Larson - Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Lauren A M Lebois - Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA
Ifat Levy - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA
Gen Li - Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Vincent A Magnotta - Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA
Antje Manthey - Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Geoffrey May - Department of Psychiatry and Behavioral Science, Texas A&M University College of Medicine, College Station, TX, USA
Katie A McLaughlin - Department of Psychology, Harvard University, Boston, MA, USA
Sven C Mueller - Department of Personality, Psychological Assessment and Treatment, University of Deusto, Bilbao, Spain
Laura Nawijn - Department of Psychiatry, Amsterdam University Medical Centers, Location VU University Medical Center, VU University, Amsterdam, The Netherlands
Steven M Nelson - Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA
Yuval Neria - New York State Psychiatric Institute, New York, NY, USA
Jack B Nitschke - Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
Miranda Olff - ARQ National Psychotrauma Centrum, Diemen, The Netherlands
Elizabeth A Olson - Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA
Matthew Peverill - Department of Psychology, University of Washington, Seattle, WA, USA
K Luan Phan - Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, IL, USA
Faisal M Rashid - Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Kerry Ressler - Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA
Isabelle M Rosso - Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA
Kelly Sambrook - Department of Radiology, University of Washington, Seattle, WA, USA
Christian Schmahl - Department of Psychiatry, University of Western Ontario, London, ON, Canada
Martha E Shenton - Department of Radiology, Harvard Medical School, Boston, MA, USA
Anika Sierk - Institute of Cognitive Neuroscience, University College London, London, United Kingdom
Jeffrey S Simons - Department of Psychology, University of South Dakota, Vermillion, SD, USA
Raluca M Simons - Department of Psychology, University of South Dakota, Vermillion, SD, USA
Scott R Sponheim - Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
Murray B Stein - Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA
Dan J Stein - SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Jennifer S Stevens - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Thomas Straube - Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
Benjamin Suarez-Jimenez - New York State Psychiatric Institute, New York, NY, USA
Marijo Tamburrino - Department of Psychiatry, University of Toledo, Toledo, OH, USA
Sophia I Thomopoulos - Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Nic J A van der Wee - Leiden Institute for Brain and Cognition, Leiden, The Netherlands
Steven J A van der Werff - Leiden Institute for Brain and Cognition, Leiden, The Netherlands
Theo G M van Erp - Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA
Sanne J H van Rooij - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Mirjam van Zuiden - Department of Psychiatry, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands
Tim Varkevisser - Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
Dick J Veltman - Department of Psychiatry, Amsterdam University Medical Centers, Location VU University Medical Center, VU University, Amsterdam, The Netherlands
Robert R J M Vermeiren - Youz-Parnassia Group, Leiden, The Netherlands
Henrik Walter - Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Li Wang - Laboratory for Traumatic Stress Studies, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Ye Zhu - Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Xi Zhu - New York State Psychiatric Institute, New York, NY, USA
Paul M Thompson - Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Rajendra A Morey - VISN 6 MIRECC, Durham VA Health Care System, Durham, NC, USA
Israel Liberzon - Department of Psychiatry and Behavioral Science, Texas A&M University College of Medicine, College Station, TX, USA
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.26(8), pp.4331-4343
DOI: 10.1038/s41380-020-00967-1
PMID: 33288872
PMCID: PMC8180531
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Publisher: England
Grant note: WA 1539/8-2 / Deutsche Forschungsgemeinschaft (German Research Foundation) K99NS096116 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) P30HD003352 / U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R21 MH098198 / NIMH NIH HHS K23 MH090366 / NIMH NIH HHS MH101380 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K24DA028773 / U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R56AG058854 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) R56 AG058854 / NIA NIH HHS HD071982 / U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) SFB/ TRR 58: C06, C07 / Deutsche Forschungsgemeinschaft (German Research Foundation) R01MH103291 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) VA CSR&D 1IK2CX001680 / U.S. Department of Veterans Affairs (Department of Veterans Affairs) R01MH63407 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01 MH117601 / NIMH NIH HHS W81XWH-08-2-0159 / U.S. Department of Defense (United States Department of Defense) R01 MH116147 / NIMH NIH HHS T32MH018931 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH105535 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) W81XWH-10-1-0925 / U.S. Department of Defense (United States Department of Defense) 40-00812-98-10041 / ZonMw (Netherlands Organisation for Health Research and Development) R56 MH071537 / NIMH NIH HHS K23 MH101380 / NIMH NIH HHS W81XWH-12-2-0012 / U.S. Department of Defense (United States Department of Defense) U54 EB020403 / NIBIB NIH HHS UL1 TR000454 / NCATS NIH HHS W81XWH08-2-0159 / U.S. Department of Defense (United States Department of Defense) 01J05415 / Bijzonder Onderzoeksfonds (Special Research Fund) R01 MH111671 / NIMH NIH HHS L30 MH114379 / NIMH NIH HHS R01AG05987 / U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) K01 MH118467 / NIMH NIH HHS K01 MH118428 / NIMH NIH HHS K99 NS096116 / NINDS NIH HHS R01 MH103291 / NIMH NIH HHS R01MH105355-01A / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH071537 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01 MH105535 / NIMH NIH HHS VA RR&D 1IK2RX000709 / U.S. Department of Veterans Affairs (Department of Veterans Affairs) K01MH118428 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MJFF14848 / Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) DA 1222/4-1 / Deutsche Forschungsgemeinschaft (German Research Foundation) R01MH110483 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) UL1TR000454 / U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) R21MH098198 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH043454 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 5U01AA021681-08 / U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) K24MH71434 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) CX001600 VA CDA / U.S. Department of Veterans Affairs (Department of Veterans Affairs) R01MH105355 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH61744 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) U01 AA021681 / NIAAA NIH HHS R01AA12479 / U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) MH098212 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH116147 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) K24 DA028773 / NIDA NIH HHS P41 EB015922 / NIBIB NIH HHS R01MH111671 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) F32MH109274 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH111671 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01 MH110483 / NIMH NIH HHS 1R21MH102634 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 110614 / Academisch Medisch Centrum (Academic Medical Center) HD085850 / U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) IK2 RX002922 / RRD VA R01MH117601 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K24 MH071434 / NIMH NIH HHS 1073041 / Department of Health | National Health and Medical Research Council (NHMRC) R21 MH102634 / NIMH NIH HHS M01RR00039 / U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR) K23 MH090366-01 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01 MH105355 / NIMH NIH HHS R21 MH098212 / NIMH NIH HHS T32 MH018931 / NIMH NIH HHS
Language: English
Date published: 12/07/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984066388602771

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