Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study.
| Title: | Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study. |
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| Authors: | 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.; Baird CL; 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 Psychology, Pennsylvania State University, State College, Pennsylvania.; Huggins AA; Department of Psychology, University of Arizona, Tucson, Arizona.; Russell CC; 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.; 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.; Rangel-Jimenez L; 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.; Abdallah CG; Department of Psychiatry, Baylor College of Medicine, Houston, Texas.; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.; Angstadt M; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.; May G; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.; Department of Psychology and Neuroscience, Baylor University, Waco, Texas.; Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, Texas.; Berg H; Department of Psychology, University of Minnesota, Minneapolis, Minnesota.; Blackford JU; University of Nebraska Medical Center, Munroe-Meyer Institute, Omaha, Nebraska.; Cisler J; Department of Psychiatry, University of Texas at Austin, Austin, Texas.; Daniels JK; Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands.; Davenport ND; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.; Davidson RJ; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisconsin.; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.; Department of Psychology, University of Wisconsin-Madison, Madison, Wisconsin.; Densmore M; Department of Psychiatry, Western University, London, Ontario, Canada.; Disner SG; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.; El-Hage W; UMR1253, Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM), Tours, France.; CIC1415, CHRU de Tours, INSERM, Tours, France.; Etkin A; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, California.; VA Palo Alto Health Care System, Palo Alto, California.; Fani N; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Frijling JL; De Viersprong, Netherlands Institute for Personality Disorders, Amsterdam, the Netherlands.; Amsterdam University Medical Center (UMC) University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; Gordon EM; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.; Grupe DW; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisconsin.; Herringa RA; School of Medicine and Public Health, University of Wisconsin Madison, Madison, Wisconsin.; Herzog JI; Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.; Hofmann D; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Hudson AR; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Jovanovic T; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan.; King A; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.; Koch SBJ; Amsterdam University Medical Center (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.; Lanius RA; Department of Psychiatry, Western University, London, Ontario, Canada.; Department of Neuroscience, Western University, London, Ontario, Canada.; Lazarov A; Tel Aviv University, Tel Aviv-Yafo, Israel.; Department of Psychiatry, Columbia University Medical Center, New York, New York.; 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.; Liberzon I; Department of Psychiatry, Texas A&M University, Bryan, Texas.; Lissek S; Department of Psychology, University of Minnesota, Minneapolis, Minnesota.; Lu G; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Manthey A; Charité Universitätsmedizin Berlin, Berlin, Germany.; Maron-Katz A; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Palo Alto, California.; McLaughlin KA; Department of Psychology, Harvard University, Cambridge, Massachusetts.; Mueller SC; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.; Nawijn L; Amsterdam University Medical Center (UMC) University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; Department of Clinical Psychology, Leiden University, Leiden, the Netherlands.; Nelson SM; Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.; Department of Psychology and Neuroscience, Baylor University, Waco, Texas.; Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, Texas.; Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, Texas.; Neria Y; New York State Psychiatric Institute, New York, New York.; Department of Psychiatry, Columbia University Medical Center, New York, New York.; Neufeld RWJ; Department of Psychiatry, Western University, London, Ontario, Canada.; Nitschke JB; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.; Olatunji BO; Department of Psychology, Vanderbilt University, Nashville, Tennessee.; Olff M; Amsterdam University Medical Center (UMC) University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; ARQ National Psychotrauma Centre, Diemen, the Netherlands.; Peverill M; Department of Psychology, University of Washington, Seattle, Washington.; Qi R; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.; Quidé Y; School of Psychology, University of New South Wales Sydney, Sydney, New South Wales, Australia.; Neuroscience Research Australia, Randwick, New South Wales, Australia.; Ravid O; New York State Psychiatric Institute, New York, New York.; Rektor I; Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republicia.; Ressler KJ; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts.; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.; Říha P; Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republicia.; First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republicia.; Ross M; Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, Illinois.; Sambrook K; Department of Radiology, University of Washington, Seattle, Washington.; Schmahl C; Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.; Sierk A; University Medical Centre Charité, Berlin, Germany.; Sponheim SR; Minneapolis VA Health Care System, Minneapolis, Minnesota.; Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.; Stevens JS; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; Straube T; Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.; Suarez-Jimenez B; Department of Neuroscience, University of Rochester Medical Center, Rochester, New York.; Théberge J; Department of Psychiatry, Western University, London, Ontario, Canada.; 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.; van Rooij SJH; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.; van Zuiden M; Amsterdam University Medical Center (UMC) University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; Department of Clinical Psychology, Utrecht University, Utrecht, the Netherlands.; Veltman DJ; Amsterdam University Medical Center (UMC) University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands.; Vermeiren RRJM; Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.; Walter H; University Medical Centre Charité, Berlin, Germany.; Wang L; 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.; Zhu X; Department of Psychiatry, Columbia University Medical Center, New York, New York.; Department of Bioengineering, University of Texas at Arlington, Arlington, Texas.; 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.; Zilcha-Mano S; Department of Psychology, University of Haifa, Haifa, Israel.; Jahanshad N; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, California.; Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, 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. |
| Source: | Biological psychiatry global open science [Biol Psychiatry Glob Open Sci] 2025 Dec 18; Vol. 6 (2), pp. 100679. Date of Electronic Publication: 2025 Dec 18 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc. on behalf of Society of Biological Psychiatry Country of Publication: United States NLM ID: 9918227369306676 Publication Model: eCollection Cited Medium: Internet ISSN: 2667-1743 (Electronic) Linking ISSN: 26671743 NLM ISO Abbreviation: Biol Psychiatry Glob Open Sci Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [New York] : Elsevier Inc. on behalf of Society of Biological Psychiatry, [2021]- |
| Abstract: | Background: Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification.; Methods: Gyrification was quantified using FreeSurfer's Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD n = 789, control n = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium) PTSD working group. Using a region of interest-based approach, we fitted a linear mixed-effects model with age (mean = 35.6, SD = 9.23, range = 8-95), sex (female = 967 [52%], male = 909 [48%]), pial surface area, PTSD, and random site effects to test associations between PTSD diagnosis/severity and regional lGI. We examined moderating effects of depression, childhood trauma, age, and sex.; Results: PTSD diagnosis and severity were both associated with lower lGI for the right medial orbitofrontal and right rostral anterior cingulate cortices. The interaction of PTSD and age was associated with lower lGI for the rostral middle frontal cortex bilaterally. Contrasting comorbid PTSD and major depressive disorder with the PTSD-only group showed that comorbidity was associated with lower lGI in the left inferior and medial temporal cortices.; Conclusions: Lower lGI, which is associated with impaired signaling efficiency, was observed in the PTSD group compared with the control group for the ventromedial prefrontal cortex, a region that has been strongly implicated in associative fear learning and extinction. It is possible that PTSD accelerates the typical age-associated decline in lGI of the rostral middle frontal cortices.; (© 2025 The Authors.) |
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| Grant Information: | P30 HD003352 United States HD NICHD NIH HHS; R01 MH043454 United States MH NIMH NIH HHS; T32 MH018931 United States MH NIMH NIH HHS |
| Contributed Indexing: | Keywords: Cortex; ENIGMA Consortium Gyrification; Neuroimaging; PTSD Ventromedial prefrontal cortex; Local Abstract: [plain-language-summary] Posttraumatic stress disorder (PTSD) involves difficulty regulating fear, but the underlying brain structure remains largely unexplored. Analyzing MRI scans from 1876 individuals worldwide, in this study, we examined cortical gyrification, which is the complex folding of the brain’s surface. We found that PTSD was associated with reduced folding in the ventromedial prefrontal cortex, a key region for emotional control. This hypogyrification was linked to greater symptom severity, independent of age or sex. These findings suggest that altered brain folding patterns may contribute to the emotional dysregulation central to PTSD, highlighting a potential structural signature of the disorder. |
| Entry Date(s): | Date Created: 20260213 Date Completed: 20260213 Latest Revision: 20260307 |
| Update Code: | 20260307 |
| PubMed Central ID: | PMC12892079 |
| DOI: | 10.1016/j.bpsgos.2025.100679 |
| PMID: | 41685071 |
| Database: | MEDLINE |
Journal Article