Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup

Nathaniel G Harnett¹, Soumyaa Joshi², Poornima Kumar³, Courtney Russell⁴, Daniel G Dillon⁵, Justin T Baker⁶, Diego A Pizzagalli⁷, Milissa L Kaufman⁸, Lisa N Nickerson⁹, Neda Jahanshad¹⁰, Lauren E Salminen¹⁰, Sophia I Thomopoulos¹⁰, Jessie L Frijling¹¹, Dick J Veltman¹², Saskia B J Koch¹³, Laura Nawijn¹⁴, Mirjam van Zuiden¹⁵, Ye Zhu¹⁶, Gen Li¹⁶, Jonathan Ipser¹⁷, Xi Zhu¹⁸, Orren Ravid¹⁹, Sigal Zilcha-Mano²⁰, Amit Lazarov²¹, Benjamin Suarez-Jimenez²², Delin Sun²³, Ahmed Hussain⁴, Ashley A Huggins²⁴, Tanja Jovanovic²⁵, Sanne J H van Rooij²⁶, Negar Fani²⁶, Anna R Hudson²⁷, Anika Sierk²⁸, Antje Manthey²⁸, Henrik Walter²⁸, Nic J A van der Wee²⁹, Steven J A van der Werff²⁹, Robert R J M Vermeiren³⁰, Pavel Říha³¹, Lauren A M Lebois³², Isabelle M Rosso³³, Elizabeth A Olson³⁴, Israel Liberzon³⁵, Mike Angstadt³⁶, Seth G Disner³⁷, Scott R Sponheim³⁸, Sheri-Michelle Koopowitz¹⁷, David Hofmann³⁹, Rongfeng Qi⁴⁰, Adi Maron-Katz⁴¹, Austin Kunch⁴², Hong Xie⁴², Wissam El-Hage⁴³, Hannah Berg⁴⁴, Steven E Bruce⁴⁵, Katie A McLaughlin⁴⁶, Matthew Peverill⁴⁷, Kelly Sambrook⁴⁸, Marisa Ross⁴⁹, Ryan J Herringa⁵⁰, Jack B Nitschke⁵¹, Richard J Davidson⁵², Terri A deRoon-Cassini⁵³, Carissa W Tomas⁵⁴, Jacklynn M Fitzgerald⁵⁵, Jennifer Urbano Blackford⁵⁶, Bunmi O Olatunji⁵⁷, Steven M Nelson⁵⁸, Evan M Gordon⁵⁹, Maria Densmore⁶⁰, Jean Théberge⁶⁰, Richard W J Neufeld⁶⁰, Miranda Olff⁶¹, Li Wang⁶², Dan J Stein¹⁷, Yuval Neria⁶³, Jennifer S Stevens²⁶, Sven C Mueller²⁷, Judith K Daniels⁶⁴, Ivan Rektor⁶⁵, Anthony King⁶⁶, Nicholas D Davenport³⁸, Thomas Straube³⁹, Guangming Lu⁴⁰, Amit Etkin⁶⁷, Xin Wang⁴², Yann Quidé⁶⁸, Shmuel Lissek⁴⁴, Josh Cisler⁶⁹, Daniel W Grupe⁷⁰, Christine Larson⁷¹, Brandee Feola⁷², Geoffrey May⁷³, Chadi G Abdallah⁷⁴, Ruth Lanius⁷⁵, Paul M Thompson¹⁰, Rajendra A Morey⁷⁶, Kerry Ressler³

Affiliations

¹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: nharnett@mclean.harvard.edu.
² Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
³ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁴ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁵ Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont MA, USA Harvard Medical School, Boston MA, USA.
⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
⁷ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Noel Drury, M.D. Institute for Translational Depression Discoveries, University of California, CA, USA.
⁸ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁹ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Applied Neuroimaging Statistics Research Laboratory, McLean Hospital, Belmont, MA, USA.
¹⁰ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
¹¹ De Viersprong mental health specialist in personality disorders, family and behavior, Amsterdam, The Netherlands; Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹² Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹³ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹⁴ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Department of Clinical Psychology, Leiden University, Leiden, The Netherlands.
¹⁵ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Department of Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
¹⁶ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁷ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁸ Department of Bioengineering, The University of Texas at Arlington, TX, USA; New York State Psychiatric Institute, New York, NY, USA.
¹⁹ New York State Psychiatric Institute, New York, NY, USA.
²⁰ University of Haifa, Haifa, Israel.
²¹ Tel-Aviv University, Tel Aviv-Yafo, Israel; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
²² Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
²³ Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA; Brain Imaging and Analysis Center, Duke University, Durham, NC, USA; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
²⁴ Department of Psychology, University of Arizona, Tucson, AZ, USA.
²⁵ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁶ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁷ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁸ University Medical Centre Charité, Berlin, Germany.
²⁹ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
³⁰ Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³¹ First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic; CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic; Division of Womens Mental Health, McLean Hospital, Belmont, MA, USA.
³² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
³³ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁴ Crisis Text Line; Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁵ Department of Psychiatry, Texas A&M University, Bryan, TX, USA.
³⁶ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
³⁷ Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
³⁸ Minneapolis VA Health Care System, Minneapolis, MN, USA.
³⁹ Institute of Medical Psychology and Systems Neuroscience, University of Munster, Munster, Germany.
⁴⁰ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
⁴¹ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA.
⁴² Department of Neurosciences and Psychiatry, University of Toledo, Toledo, OH, USA.
⁴³ Université de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
⁴⁴ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴⁵ University of Missouri-St. Louis, Department of Psychological Sciences, Center for Trauma Recovery, St. Louis, MO, USA.
⁴⁶ Department of Psychology, Harvard University, Cambridge, MA, USA.
⁴⁷ Department of Psychology, University of Washington, Seattle, WA, USA.
⁴⁸ Department of Radiology, University of Washington, Seattle, WA, USA.
⁴⁹ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁵⁰ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁵¹ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵² Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵³ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, WI, USA; Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁵⁴ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin, WI, USA; Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁵⁵ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁵⁶ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁷ Department of Psychology, Vanderbilt University, TN, USA.
⁵⁸ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA; Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁵⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁶⁰ Department of Psychiatry, Western University, London, ON, Canada.
⁶¹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; ARQ National Psychotrauma Centre, Diemen, The Netherlands.
⁶² State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
⁶³ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; New York State Psychiatric Institute, New York, NY, USA.
⁶⁴ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands; GGZ Drenthe Mental Health Institute, Department Trauma Center.
⁶⁵ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
⁶⁶ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁶⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA.
⁶⁸ School of Psychology, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia.
⁶⁹ Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁷⁰ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁷¹ Department of Psychology, University of Wisconsin- Milwaukee, Milwaukee, WI, USA.
⁷² Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷³ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA; Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA; Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁷⁴ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁷⁵ Department of Neuroscience, Western University, London, ON, Canada; Department of Psychiatry, Western University, London, ON, Canada.
⁷⁶ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.

PMID: 40712699
PMCID: PMC12404044 (available on 2026-07-23)
DOI: 10.1016/j.bpsc.2025.07.005

Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup

Nathaniel G Harnett et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025.

. 2025 Jul 23:S2451-9022(25)00221-6.

doi: 10.1016/j.bpsc.2025.07.005. Online ahead of print.

Authors

Affiliations

¹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: nharnett@mclean.harvard.edu.
² Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
³ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁴ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁵ Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont MA, USA Harvard Medical School, Boston MA, USA.
⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
⁷ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Noel Drury, M.D. Institute for Translational Depression Discoveries, University of California, CA, USA.
⁸ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁹ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Applied Neuroimaging Statistics Research Laboratory, McLean Hospital, Belmont, MA, USA.
¹⁰ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
¹¹ De Viersprong mental health specialist in personality disorders, family and behavior, Amsterdam, The Netherlands; Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹² Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹³ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹⁴ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Department of Clinical Psychology, Leiden University, Leiden, The Netherlands.
¹⁵ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Department of Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
¹⁶ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁷ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁸ Department of Bioengineering, The University of Texas at Arlington, TX, USA; New York State Psychiatric Institute, New York, NY, USA.
¹⁹ New York State Psychiatric Institute, New York, NY, USA.
²⁰ University of Haifa, Haifa, Israel.
²¹ Tel-Aviv University, Tel Aviv-Yafo, Israel; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
²² Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
²³ Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA; Brain Imaging and Analysis Center, Duke University, Durham, NC, USA; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
²⁴ Department of Psychology, University of Arizona, Tucson, AZ, USA.
²⁵ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁶ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁷ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁸ University Medical Centre Charité, Berlin, Germany.
²⁹ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
³⁰ Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³¹ First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic; CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic; Division of Womens Mental Health, McLean Hospital, Belmont, MA, USA.
³² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
³³ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁴ Crisis Text Line; Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁵ Department of Psychiatry, Texas A&M University, Bryan, TX, USA.
³⁶ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
³⁷ Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
³⁸ Minneapolis VA Health Care System, Minneapolis, MN, USA.
³⁹ Institute of Medical Psychology and Systems Neuroscience, University of Munster, Munster, Germany.
⁴⁰ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
⁴¹ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA.
⁴² Department of Neurosciences and Psychiatry, University of Toledo, Toledo, OH, USA.
⁴³ Université de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
⁴⁴ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴⁵ University of Missouri-St. Louis, Department of Psychological Sciences, Center for Trauma Recovery, St. Louis, MO, USA.
⁴⁶ Department of Psychology, Harvard University, Cambridge, MA, USA.
⁴⁷ Department of Psychology, University of Washington, Seattle, WA, USA.
⁴⁸ Department of Radiology, University of Washington, Seattle, WA, USA.
⁴⁹ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁵⁰ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁵¹ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵² Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵³ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, WI, USA; Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁵⁴ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin, WI, USA; Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁵⁵ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁵⁶ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁷ Department of Psychology, Vanderbilt University, TN, USA.
⁵⁸ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA; Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁵⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁶⁰ Department of Psychiatry, Western University, London, ON, Canada.
⁶¹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; ARQ National Psychotrauma Centre, Diemen, The Netherlands.
⁶² State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
⁶³ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; New York State Psychiatric Institute, New York, NY, USA.
⁶⁴ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands; GGZ Drenthe Mental Health Institute, Department Trauma Center.
⁶⁵ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
⁶⁶ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁶⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA.
⁶⁸ School of Psychology, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia.
⁶⁹ Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁷⁰ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁷¹ Department of Psychology, University of Wisconsin- Milwaukee, Milwaukee, WI, USA.
⁷² Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷³ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA; Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA; Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁷⁴ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁷⁵ Department of Neuroscience, Western University, London, ON, Canada; Department of Psychiatry, Western University, London, ON, Canada.
⁷⁶ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.

PMID: 40712699
PMCID: PMC12404044 (available on 2026-07-23)
DOI: 10.1016/j.bpsc.2025.07.005

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 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.

Keywords: PTSD; Structural MRI; Trauma; Ventral visual stream.

PubMed Disclaimer

Conflict of interest statement

Disclosures: A preprint version of the manuscript is available in medRxiv: https://doi.org/10.1101/2025.03.18.25324188. Over the past 3 years, Dr. Pizzagalli has received consulting fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Karla Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Sage Therapeutics, and Takeda; he has received honoraria from the American Psychological Association, Psychonomic Society and Springer (for editorial work) and Alkermes; he has received research funding from the Bird Foundation, Brain and Behavior Research Foundation, Dana Foundation, Millennium Pharmaceuticals, NIMH, and Wellcome Leap; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. Dr. Lebois reports unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation (ISSTD), grant support from the National Institute of Mental Health, K01 MH118467, spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals, and spousal employment at Violet Therapeutics, all unrelated to the present work. Dr. El-Hage reports payments from Air Liquide, CHUGAI, EISAI, Jazz Pharmaceuticals, Janssen, Lundbeck, Otsuka, UCB unrelated to the present work. Dr. Herringa reports consultancy work for Jazz Pharmaceuticals. Dr. Davidson is the founder and president of, and serves on the board of directors for, the non-profit organization Healthy Minds Innovations, Inc. Dr. Abdallah has served as a consultant, speaker and/or on advisory boards for Douglas Pharmaceutical, Freedom Biosciences, FSV7, Lundbeck, Psilocybin Labs, Genentech, and Janssen; and received royalties for a patent on using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). Dr. Olsen reports employment at CrisisHealthLine. All other authors report no biomedical financial interests or potential conflicts of interest. All views expressed are solely those of the authors.

Update of

Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.
Harnett NG, Joshi S, Kumar P, Russell C, Dillon DG, Baker JT, Pizzagalli DA, Kaufman ML, Nickerson LN, Jahanshad N, Salminen LE, Thomopoulos SI, Frijling JL, Veltman DJ, Koch SBJ, Nawijn L, van Zuiden M, Zhu Y, Li G, Ipser J, Zhu X, Ravid O, Zilcha-Mano S, Lazarov A, Suarez-Jimenez B, Sun D, Hussain A, Huggins AA, Jovanovic T, van Rooij SJH, Fani N, Hudson AR, Sierk A, Manthey A, Walter H, van der Wee NJA, van der Werff SJA, Vermeiren RRJM, Říha P, Lebois LAM, Rosso IM, Olson EA, Liberzon I, Angstadt M, Disner SG, Sponheim SR, Koopowitz SM, Hofmann D, Qi R, Maron-Katz A, Kunch A, Xie H, El-Hage W, Berg H, Bruce SE, McLaughlin KA, Peverill M, Sambrook K, Ross M, Herringa RJ, Nitschke JB, Davidson RJ, deRoon-Cassini TA, Tomas CW, Fitzgerald JM, Blackford JU, Olatunji BO, Nelson SM, Gordon EM, Densmore M, Théberge J, Neufeld RWJ, Olff M, Wang L, Stein DJ, Neria Y, Stevens JS, Mueller SC, Daniels JK, Rektor I, King A, Davenport ND, Straube T, Lu G, Etkin A, Wang X, Quidé Y, Lissek S, Cisler J, Grupe DW, Larson C, Feola B, May G, Abdallah CG, Lanius R, Thompson PM, Morey RA, Ressler K. Harnett NG, et al. medRxiv [Preprint]. 2025 Mar 19:2025.03.18.25324188. doi: 10.1101/2025.03.18.25324188. medRxiv. 2025. Update in: Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Jul 23:S2451-9022(25)00221-6. doi: 10.1016/j.bpsc.2025.07.005. PMID: 40166540 Free PMC article. Updated. Preprint.

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Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup

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Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup

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