ArticlemedRxiv : the preprint server for health sciences2025
Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.
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98 authors.
Nathaniel G HarnettDivision of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
Soumyaa JoshiDivision of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
Poornima KumarDivision of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
Courtney RussellBrain Imaging and Analysis Center, Duke University, Durham, NC, USA.
Daniel G DillonCenter for Depression, Anxiety and Stress Research, McLean Hospital, Belmont MA, USA Harvard Medical School, Boston MA, USA.
Justin T BakerDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Diego A PizzagalliDivision of Depression and Anxiety, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Milissa L KaufmanDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Lisa N NickersonDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.ORCID 0000-0003-4401-8950
Lauren E SalminenImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.ORCID 0000-0002-0046-4070
Jessie L FrijlingDe Viersprong mental health specialist in personality disorders, family and behavior, Amsterdam, The Netherlands.
Dick J VeltmanAmsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Saskia B J KochAmsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Laura NawijnAmsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Mirjam van ZuidenAmsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Ye ZhuLaboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Gen LiLaboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Jonathan IpserSA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Xi ZhuDepartment of Bioengineering, The University of Texas at Arlington, TX, USA.
Orren RavidNew York State Psychiatric Institute, New York, NY, USA.
Sigal Zilcha-ManoUniversity of Haifa, Haifa, Israel.
Amit LazarovTel-Aviv University, Tel Aviv-Yafo, Israel.ORCID 0000-0002-2811-2739
Benjamin Suarez-JimenezDepartment of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
Delin SunDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.
Ahmed HussainBrain Imaging and Analysis Center, Duke University, Durham, NC, USA.
Ashley A HugginsDepartment of Psychology, University of Arizona, Tucson, AZ, USA.ORCID 0000-0001-7936-2116
Tanja JovanovicDepartment of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
Sanne J H van RooijDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Negar FaniDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Anna R HudsonDepartment of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
Anika SierkUniversity Medical Centre Charité, Berlin, Germany.
Antje MantheyUniversity Medical Centre Charité, Berlin, Germany.
Henrik WalterUniversity Medical Centre Charité, Berlin, Germany.
Nic J A van der WeeDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-3235-1633
Steven J A van der WerffDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Robert R J M VermeirenDepartment of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Pavel ŘíhaFirst Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Lauren A M LeboisDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5816-9181
Isabelle M RossoDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Elizabeth A OlsonCrisis Text Line.ORCID 0000-0003-4617-8050
Israel LiberzonDepartment of Psychiatry, Texas A&M University, Bryan, TX, USA.
Mike AngstadtDepartment of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Seth G DisnerMinneapolis VA Health Care System, Minneapolis, MN, USA.
Scott R SponheimMinneapolis VA Health Care System, Minneapolis, MN, USA.
Sheri-Michelle KoopowitzSA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-5151-9692
David HofmannInstitute of Medical Psychology and Systems Neuroscience, University of Mu nster, Mu nster, Germany.
Rongfeng QiDepartment of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Adi Maron-KatzDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA.
Austin KunchDepartment of Neurosciences and Psychiatry, University of Toledo, Toledo, OH, USA.
Hong XieDepartment of Neurosciences and Psychiatry, University of Toledo, Toledo, OH, USA.
Wissam El-HageUniversité de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
Hannah BergDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.
Steven E BruceUniversity of Missouri-St. Louis, Department of Psychological Sciences, Center for Trauma Recovery, St. Louis, MO, USA.
Katie A McLaughlinDepartment of Psychology, Harvard University, Cambridge, MA, USA.
Matthew PeverillDepartment of Psychology, University of Washington, Seattle, WA, USA.
Kelly SambrookDepartment of Radiology, University of Washington, Seattle, WA, USA.
Marisa RossNorthwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
Ryan J HerringaSchool of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
Jack B NitschkeDepartment of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
Richard J DavidsonCenter for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-8506-4964
Terri A deRoon-CassiniDepartment of Surgery, Medical College of Wisconsin, WI, USA.
Carissa W TomasDivision of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin, WI, USA.
Jacklynn M FitzgeraldDepartment of Psychology, Marquette University, Milwaukee, WI, USA, VISUAL PATHWAY STRUCTURE AND PTSD.
Jennifer Urbano BlackfordMunroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-0261-4845
Bunmi O OlatunjiDepartment of Psychology, Vanderbilt University, TN, USA.
Steven M NelsonVeterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
Evan M GordonDepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Maria DensmoreDepartment of Psychiatry, Western University, London, ON, Canada.
Jean ThébergeDepartment of Psychiatry, Western University, London, ON, Canada.
Richard W J NeufeldDepartment of Psychiatry, Western University, London, ON, Canada.
Miranda OlffAmsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.ORCID 0000-0003-1016-9515
Li WangState Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Dan J SteinSA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Yuval NeriaDepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA.
Jennifer S StevensDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Sven C MuellerDepartment of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.ORCID 0000-0003-1661-3840
Judith K DanielsDepartment of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
Ivan RektorCEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
Anthony KingDepartment of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Nicholas D DavenportMinneapolis VA Health Care System, Minneapolis, MN, USA.
Thomas StraubeInstitute of Medical Psychology and Systems Neuroscience, University of Mu nster, Mu nster, Germany.
Guangming LuDepartment of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Amit EtkinDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA.
Xin WangDepartment of Neurosciences and Psychiatry, University of Toledo, Toledo, OH, USA.
Yann QuidéSchool of Psychology, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0002-8569-7139
Shmuel LissekDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.
Josh CislerDepartment of Psychiatry, University of Texas at Austin, Austin, TX, USA.
Daniel W GrupeCenter for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
Christine LarsonDepartment of Psychology, University of Wisconsin- Milwaukee, Milwaukee, WI, USA.
Brandee FeolaDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Geoffrey MayCenter for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
Chadi G AbdallahDepartment of Psychiatry, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0001-5783-6181
Ruth LaniusDepartment of Neuroscience, Western University, London, ON, Canada.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.ORCID 0000-0002-4720-8867
Rajendra A MoreyBrain Imaging and Analysis Center, Duke University, Durham, NC, USA.
Kerry ResslerDivision of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
Funding
WISCONSIN CENTER ON MENTAL RETARDATION: CORE SUPPORTP30HD003352 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI SVAREN, JOHN P · 1985 to 2015
$25.2MX LINKED NYSTAGMUS SYNDROME WITH FEATURES OF ALBINISMM01RR000039 · NCRR · EMORY UNIVERSITY · PI VACCARINO, VIOLA · 1985 to 2007
$21.3MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1MTRAINING PROGRAM IN EMOTION RESEARCHT32MH018931 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI Richard J Davidson · 1989 to 2026
$11.6MNeurodevelopmental Mechanisms Underlying Stress Vulnerability during AdolescenceR37MH119194 · NIMH · HARVARD UNIVERSITY · PI Katie McLaughlin · 2020 to 2026
$10.6MTraining U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MNeural Substrates of Affective Style and Emotion RegulationR01MH043454 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI DAVIDSON, RICHARD J, SCHAEFER, STACEY M · 1989 to 2022
$9.6MGenetic and Trauma-Related Risk Factors for PTSDR01MH071537 · NIMH · EMORY UNIVERSITY · PI RESSLER, KERRY J. · 2005 to 2014
$8.5MTrauma and Genomics Modulate Brain Structure across Common Psychiatric DisordersR01MH111671 · NIMH · DUKE UNIVERSITY · PI MARK W LOGUE, RAJENDRA A MOREY · 2017 to 2026
$4.4MEmory University BIRCWH ProgramK12HD085850 · NICHD · EMORY UNIVERSITY · PI OFOTOKUN, IGHOVWERHA, STERK, CLAIRE E · 2015 to 2023
$4.4MChild Trauma and the Development of Neural Systems Underlying Emotion RegulationR01MH103291 · NIMH · UNIVERSITY OF WASHINGTON · PI MCLAUGHLIN, KATIE · 2014 to 2018
$3.8MStudy of early brain alterations that predict development of chronic PTSDR01MH110483 · NIMH · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI WANG, XIN · 2016 to 2021
$3.8MCSRD VA IK2 CX001680NCRR NIH HHS M01 RR000039NIA NIH HHS R01 AG059874NIA NIH HHS R56 AG058854NIBIB NIH HHS P41 EB015922NIBIB NIH HHS U54 EB020403NICHD NIH HHS K12 HD085850NICHD NIH HHS P30 HD003352NICHD NIH HHS R01 HD071982NIMH NIH HHS K01 MH118428NIMH NIH HHS K01 MH118467NIMH NIH HHS K01 MH121653NIMH NIH HHS K01 MH122774NIMH NIH HHS K01 MH129828NIMH NIH HHS K23 MH101380NIMH NIH HHS K23 MH112873NIMH NIH HHS R01 MH043454NIMH NIH HHS R01 MH071537NIMH NIH HHS R01 MH103291NIMH NIH HHS R01 MH105355NIMH NIH HHS R01 MH106574NIMH NIH HHS R01 MH110483NIMH NIH HHS R01 MH111671NIMH NIH HHS R01 MH113574NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH117601NIMH NIH HHS R01 MH119227NIMH NIH HHS R01 MH128371NIMH NIH HHS R01 MH132221NIMH NIH HHS R01 MH134004NIMH NIH HHS R21 MH098198NIMH NIH HHS R21 MH098212NIMH NIH HHS R21 MH106998NIMH NIH HHS R21 MH112956NIMH NIH HHS R37 MH119194NIMH NIH HHS R56 MH071537NIMH NIH HHS T32 MH018931RRD VA I01 RX000622RRD VA IK1 RX002325RRD VA IK2 RX000709RRD VA IK2 RX002922Wellcome Trust
Abstract
Background: Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust - and potentially a pretrauma - marker of vulnerability. Methods: We analyzed data from the ENIGMA-PTSD dataset (n = 2,814) and the Human Connectome Project - Young Adult (HCP-YA) dataset (n = 890) to investigate whether structural covariance of early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress. Results: Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms and no association was observed between loadings and perceived stress measures in the HCP-YA dataset. Conclusion: Structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.
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PTSDStructural MRITraumaVentral visual stream
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