Structural Covariance of Early Visual Cortex Is Negatively Associated With Posttraumatic Stress Disorder Symptoms: A Mega-Analysis From the ENIGMA PTSD Working Group.
| Title: | Structural Covariance of Early Visual Cortex Is Negatively Associated With Posttraumatic Stress Disorder Symptoms: A Mega-Analysis From the ENIGMA PTSD Working Group. |
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| Authors: | Harnett NG; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: nharnett@mclean.harvard.edu.; Joshi S; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts.; Kumar P; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.; Russell C; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina.; Dillon DG; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts.; Baker JT; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Institute for Technology in Psychiatry, McLean Hospital, Belmont, Massachusetts.; Pizzagalli DA; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Noel Drury, M.D. Institute for Translational Depression Discoveries, University of California Irvine, Irvine, California.; Kaufman ML; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Division of Women's Mental Health, McLean Hospital, Belmont, Massachusetts.; Nickerson LD; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Applied Neuroimaging Statistics Research Laboratory, McLean Hospital, Belmont, Massachusetts.; Jahanshad N; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.; Salminen LE; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.; Thomopoulos SI; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.; Frijling JL; De Viersprong Mental Health Specialist in Personality Disorders, Family and Behavior, Amsterdam, the Netherlands; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.; Veltman DJ; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam UMC, Amsterdam, the Netherlands.; Koch SBJ; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, the Netherlands.; Nawijn L; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Department of Clinical Psychology, Leiden University, Leiden, the Netherlands.; van Zuiden M; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Department of Clinical Psychology, Utrecht University, Utrecht, the Netherlands.; Zhu Y; 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.; Li G; 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.; Ipser J; SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Zhu X; Department of Bioengineering, The University of Texas at Arlington, Arlington, Texas; New York State Psychiatric Institute, New York, New York.; Ravid O; New York State Psychiatric Institute, New York, New York.; Zilcha-Mano S; University of Haifa, Haifa, Israel.; Lazarov A; Tel Aviv University, Tel Aviv-Yafo, Israel; Department of Psychiatry, Columbia University Medical Center, New York, New York.; Suarez-Jimenez B; Department of Neuroscience, University of Rochester Medical Center, Rochester, New York.; Sun D; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina; Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, North Carolina.; Hussain A; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina.; Huggins AA; Department of Psychology, University of Arizona, Tucson, Arizona.; Jovanovic T; Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; van Rooij SJH; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Fani N; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Hudson AR; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Sierk A; University Medical Centre Charité, Berlin, Germany.; Manthey A; University Medical Centre Charité, Berlin, Germany.; Walter H; University Medical Centre Charité, Berlin, Germany.; van der Wee NJA; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.; van der Werff SJA; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.; Vermeiren RRJM; Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.; Říha P; 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.; Lebois LAM; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts.; Rosso IM; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts.; Olson EA; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Crisis Text Line, New York, New York.; Liberzon I; Department of Psychiatry, Texas A&M University, Bryan, Texas.; Angstadt M; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.; Disner SG; Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Sponheim SR; Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Koopowitz SM; SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Hofmann D; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Qi R; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Maron-Katz A; Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California.; Kunch A; Department of Neurosciences and Psychiatry, University of Toledo, Toledo, Ohio.; Xie H; Department of Neurosciences and Psychiatry, University of Toledo, Toledo, Ohio.; El-Hage W; Université de Tours, Institut National de la Santé et de la Recherche Médicale, Imaging Brain & Neuropsychiatry iBraiN U1253, Tours, France.; Berg H; Department of Psychology, University of Minnesota, Minneapolis, Minnesota.; Bruce SE; Center for Trauma Recovery, Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, Missouri.; McLaughlin KA; Department of Psychology, Harvard University, Cambridge, Massachusetts.; Peverill M; Department of Psychology, University of Washington, Seattle, Washington.; Sambrook K; Department of Radiology, University of Washington, Seattle, Washington.; Ross M; Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, Illinois.; Herringa RJ; School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.; Nitschke JB; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.; Davidson RJ; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology, University of Wisconsin-Madison, Madison, Wisconsin.; deRoon-Cassini TA; Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin.; Tomas CW; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.; Fitzgerald JM; Department of Psychology, Marquette University, Milwaukee, Wisconsin.; Blackford JU; Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.; Olatunji BO; Department of Psychology, Vanderbilt University, Nashville, Tennessee.; Nelson SM; Veterans Integrated Service Network-17, Center of Excellence for Research on Returning War Veterans, Waco, Texas; Department of Psychology and Neuroscience, Baylor University, Waco, Texas; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, Texas.; Gordon EM; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.; Densmore M; Department of Psychiatry, Western University, London, Ontario, Canada.; Théberge J; Department of Psychiatry, Western University, London, Ontario, Canada.; Neufeld RWJ; Department of Psychiatry, Western University, London, Ontario, Canada.; Olff M; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; ARQ National Psychotrauma Centre, Diemen, the Netherlands.; Wang L; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.; Stein DJ; SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Neria Y; New York State Psychiatric Institute, New York, New York; Department of Psychiatry, Columbia University Medical Center, New York, New York.; Stevens JS; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Mueller SC; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Daniels JK; Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands; Department Trauma Center, GGZ Drenthe Mental Health Institute, Beilen, the Netherlands.; Rektor I; CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.; King A; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.; Davenport ND; Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Straube T; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Lu G; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Etkin A; Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California; VA Palo Alto Health Care System, Palo Alto, California.; Wang X; Department of Neurosciences and Psychiatry, University of Toledo, Toledo, Ohio.; Quidé Y; School of Psychology, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, Randwick, New South Wales, Australia.; Lissek S; Department of Psychology, University of Minnesota, Minneapolis, Minnesota.; Cisler J; Department of Psychiatry, University of Texas at Austin, Austin, Texas.; Grupe DW; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisconsin.; Larson C; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.; Feola B; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.; May G; Veterans Integrated Service Network-17, Center of Excellence for Research on Returning War Veterans, Waco, Texas; Department of Psychology and Neuroscience, Baylor University, Waco, Texas; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.; Abdallah CG; Department of Psychiatry, Baylor College of Medicine, Houston, Texas; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.; Lanius R; Department of Psychiatry, Western University, London, Ontario, Canada; Department of Neuroscience, Western University, London, Ontario, Canada.; Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.; Morey RA; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina.; Ressler KJ; Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. |
| Source: | Biological psychiatry. Cognitive neuroscience and neuroimaging [Biol Psychiatry Cogn Neurosci Neuroimaging] 2026 Jan; Vol. 11 (1), pp. 48-57. Date of Electronic Publication: 2025 Jul 23. |
| Publication Type: | Journal Article; Meta-Analysis |
| Language: | English |
| Journal Info: | Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 101671285 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2451-9030 (Electronic) Linking ISSN: 24519022 NLM ISO Abbreviation: Biol Psychiatry Cogn Neurosci Neuroimaging Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Elsevier, Inc., [2016]- |
| MeSH Terms: | Stress Disorders, Post-Traumatic*/diagnostic imaging ; Stress Disorders, Post-Traumatic*/physiopathology ; Stress Disorders, Post-Traumatic*/pathology ; Visual Cortex*/diagnostic imaging ; Visual Cortex*/pathology ; Visual Cortex*/physiopathology; Humans ; Adult ; Male ; Female ; Magnetic Resonance Imaging ; Young Adult ; Connectome |
| 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 that the 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-naïve individuals to determine whether such a neural signature is a robust marker of vulnerability.; Methods: We analyzed data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-PTSD dataset (N = 2814) and the HCP-YA (Human Connectome Project-Young Adult) dataset (N = 890) to investigate whether the structural covariance of the 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.; Conclusions: The 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.; (Copyright © 2025 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
| Comments: | Update of: medRxiv. 2025 Mar 19:2025.03.18.25324188. doi: 10.1101/2025.03.18.25324188.. (PMID: 40166540) |
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| Grant Information: | K01 MH121653 United States MH NIMH NIH HHS; R21 MH112956 United States MH NIMH NIH HHS; R21 MH098198 United States MH NIMH NIH HHS; R01 MH116147 United States MH NIMH NIH HHS; R01 MH095809 United States MH NIMH NIH HHS; R01 MH119227 United States MH NIMH NIH HHS; R01 MH110483 United States MH NIMH NIH HHS; T32 MH018931 United States MH NIMH NIH HHS; K01 MH118467 United States MH NIMH NIH HHS; IK2 RX000709 United States RX RRD VA; R01 AG059874 United States AG NIA NIH HHS; P41 EB015922 United States EB NIBIB NIH HHS; P30 HD003352 United States HD NICHD NIH HHS; R56 MH071537 United States MH NIMH NIH HHS; K01 MH129828 United States MH NIMH NIH HHS; K01 MH122774 United States MH NIMH NIH HHS; IK2 RX002922 United States RX RRD VA; R21 MH098212 United States MH NIMH NIH HHS; R01 MH113574 United States MH NIMH NIH HHS; K12 HD085850 United States HD NICHD NIH HHS; R01 MH071537 United States MH NIMH NIH HHS; R01 MH128371 United States MH NIMH NIH HHS; IK2 CX001680 United States CX CSRD VA; R21 MH106998 United States MH NIMH NIH HHS; K01 MH118428 United States MH NIMH NIH HHS; R01 MH105355 United States MH NIMH NIH HHS; M01 RR000039 United States RR NCRR NIH HHS; R01 MH111671 United States MH NIMH NIH HHS; R01 MH106574 United States MH NIMH NIH HHS; R01 MH132221 United States MH NIMH NIH HHS; IK1 RX002325 United States RX RRD VA; I01 RX000622 United States RX RRD VA; U54 EB020403 United States EB NIBIB NIH HHS; R01 MH117601 United States MH NIMH NIH HHS; UL1 TR000454 United States TR NCATS NIH HHS; R56 AG058854 United States AG NIA NIH HHS; K23 MH112873 United States MH NIMH NIH HHS; K23 MH101380 United States MH NIMH NIH HHS; R01 MH043454 United States MH NIMH NIH HHS; R01 HD071982 United States HD NICHD NIH HHS; United Kingdom WT_ Wellcome Trust |
| Contributed Indexing: | Keywords: PTSD; Posttraumatic stress disorder; Structural MRI; Structural covariance; Trauma; Ventral visual stream |
| Entry Date(s): | Date Created: 20250725 Date Completed: 20260107 Latest Revision: 20260306 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC12404044 |
| DOI: | 10.1016/j.bpsc.2025.07.005 |
| PMID: | 40712699 |
| Database: | MEDLINE |
Journal Article; Meta-Analysis