A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study
Abstract Background Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (...
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2025-01-01
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| author | Cheryl R.Z. See Shuqing Si C. Lexi Baird Courtney C. Haswell Ahmed Hussain Miranda Olff Dick J. Veltman Jessie L. Frijling Mirjam van Zuiden Saskia B.J. Koch Laura Nawijn Li Wang Ye Zhu Gen Li Yuval Neria Xi Zhu Benjamin Suarez-Jimenez Sigal Zilcha-Mano Amit Lazarov Jennifer S. Stevens Kerry Ressler Negar Fani Tanja Jovanovic Sanne J.H. van Rooij Milissa L. Kaufman Lauren A.M. Lebois Isabelle M. Rosso Elizabeth A. Olson Justin T. Baker Scott R. Sponheim Seth G. Disner Nicholas D. Davenport Amit Etkin Adi Maron-Katz Murray B. Stein Martha E. Shenton Dan J. Stein Jonathan Ipser Sheri-Michelle Koopowitz Soraya Seedat Stefan du Plessis Leigh L. van den Heuvel Shmuel Lissek Hannah Berg Thomas Straube David Hofman Lee A. Baugh Gina L. Forster Raluca M. Simons Jeffrey S. Simons Vincent A. Magnotta Kelene A. Fercho Xin Wang Andrew S. Cotton Erin N. O’Leary Hong Xie Daniel W. Grupe Jack B. Nitschke Richard J. Davidson Christine L. Larson Terri A. deRoon-Cassini Carissa W. Tomas Jacklynn M. Fitzgerald Jennifer Urbano Blackford Bunmi O. Olatunji Evan M. Gordon Geoffrey May Steven M. Nelson Ruth Lanius Jean Théberge Maria Densmore Richard W.J. Neufeld Chadi G. Abdallah Christopher L. Averill Ilan Harpaz-Rotem Ifat Levy John H. Krystal Elbert Geuze Remko van Lutterveld Emily L. Dennis David F. Tate David X. Cifu William C. Walker Elisabeth A. Wilde Nic J.A. van der Wee Robert R.J.M. Vermeiren Steven J.A. van der Werff Katie McLaughlin Kelly Sambrook Matthew Peverill Joaquim Radua Lauren E. Salminen Neda Jahanshad Sophia I. Thomopoulos Anthony James Lucia Valmaggia Paul M. Thompson Rajendra A. Morey Matthew J. Kempton |
| author_facet | Cheryl R.Z. See Shuqing Si C. Lexi Baird Courtney C. Haswell Ahmed Hussain Miranda Olff Dick J. Veltman Jessie L. Frijling Mirjam van Zuiden Saskia B.J. Koch Laura Nawijn Li Wang Ye Zhu Gen Li Yuval Neria Xi Zhu Benjamin Suarez-Jimenez Sigal Zilcha-Mano Amit Lazarov Jennifer S. Stevens Kerry Ressler Negar Fani Tanja Jovanovic Sanne J.H. van Rooij Milissa L. Kaufman Lauren A.M. Lebois Isabelle M. Rosso Elizabeth A. Olson Justin T. Baker Scott R. Sponheim Seth G. Disner Nicholas D. Davenport Amit Etkin Adi Maron-Katz Murray B. Stein Martha E. Shenton Dan J. Stein Jonathan Ipser Sheri-Michelle Koopowitz Soraya Seedat Stefan du Plessis Leigh L. van den Heuvel Shmuel Lissek Hannah Berg Thomas Straube David Hofman Lee A. Baugh Gina L. Forster Raluca M. Simons Jeffrey S. Simons Vincent A. Magnotta Kelene A. Fercho Xin Wang Andrew S. Cotton Erin N. O’Leary Hong Xie Daniel W. Grupe Jack B. Nitschke Richard J. Davidson Christine L. Larson Terri A. deRoon-Cassini Carissa W. Tomas Jacklynn M. Fitzgerald Jennifer Urbano Blackford Bunmi O. Olatunji Evan M. Gordon Geoffrey May Steven M. Nelson Ruth Lanius Jean Théberge Maria Densmore Richard W.J. Neufeld Chadi G. Abdallah Christopher L. Averill Ilan Harpaz-Rotem Ifat Levy John H. Krystal Elbert Geuze Remko van Lutterveld Emily L. Dennis David F. Tate David X. Cifu William C. Walker Elisabeth A. Wilde Nic J.A. van der Wee Robert R.J.M. Vermeiren Steven J.A. van der Werff Katie McLaughlin Kelly Sambrook Matthew Peverill Joaquim Radua Lauren E. Salminen Neda Jahanshad Sophia I. Thomopoulos Anthony James Lucia Valmaggia Paul M. Thompson Rajendra A. Morey Matthew J. Kempton |
| author_sort | Cheryl R.Z. See |
| collection | DOAJ |
| description |
Abstract
Background
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p
corrected
= .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p
corrected
= .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
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| format | Article |
| id | doaj-art-8dcc74c27e014b18b8d7d2f1dc3fbb6f |
| institution | Matheson Library |
| issn | 0924-9338 1778-3585 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | European Psychiatry |
| spelling | doaj-art-8dcc74c27e014b18b8d7d2f1dc3fbb6f2025-07-28T04:20:44ZengCambridge University PressEuropean Psychiatry0924-93381778-35852025-01-016810.1192/j.eurpsy.2025.10062A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC studyCheryl R.Z. See0https://orcid.org/0000-0003-2135-5495Shuqing Si1https://orcid.org/0009-0006-6095-254XC. Lexi Baird2Courtney C. Haswell3Ahmed Hussain4https://orcid.org/0009-0005-8761-7525Miranda Olff5Dick J. Veltman6Jessie L. Frijling7Mirjam van Zuiden8Saskia B.J. Koch9https://orcid.org/0000-0002-3628-6712Laura Nawijn10Li Wang11https://orcid.org/0000-0002-1459-3412Ye Zhu12Gen Li13Yuval Neria14Xi Zhu15Benjamin Suarez-Jimenez16https://orcid.org/0000-0002-4765-2458Sigal Zilcha-Mano17Amit Lazarov18https://orcid.org/0000-0002-2811-2739Jennifer S. Stevens19Kerry Ressler20https://orcid.org/0000-0002-5158-1103Negar Fani21Tanja Jovanovic22Sanne J.H. van Rooij23Milissa L. Kaufman24Lauren A.M. Lebois25https://orcid.org/0000-0001-5816-9181Isabelle M. Rosso26Elizabeth A. Olson27Justin T. Baker28Scott R. Sponheim29Seth G. Disner30https://orcid.org/0000-0003-3635-9421Nicholas D. Davenport31Amit Etkin32Adi Maron-Katz33Murray B. Stein34Martha E. Shenton35Dan J. Stein36https://orcid.org/0000-0001-7218-7810Jonathan Ipser37Sheri-Michelle Koopowitz38https://orcid.org/0000-0002-5151-9692Soraya Seedat39Stefan du Plessis40Leigh L. van den Heuvel41Shmuel Lissek42Hannah Berg43Thomas Straube44David Hofman45https://orcid.org/0000-0003-3494-634XLee A. Baugh46https://orcid.org/0000-0001-6227-497XGina L. Forster47Raluca M. Simons48Jeffrey S. Simons49Vincent A. Magnotta50https://orcid.org/0000-0001-8639-5354Kelene A. Fercho51https://orcid.org/0000-0003-0577-186XXin Wang52Andrew S. Cotton53Erin N. O’Leary54Hong Xie55Daniel W. Grupe56Jack B. Nitschke57Richard J. Davidson58Christine L. Larson59https://orcid.org/0000-0002-1359-6080Terri A. deRoon-Cassini60Carissa W. Tomas61https://orcid.org/0000-0002-9199-8632Jacklynn M. Fitzgerald62Jennifer Urbano Blackford63https://orcid.org/0000-0002-0261-4845Bunmi O. Olatunji64Evan M. Gordon65Geoffrey May66Steven M. Nelson67Ruth Lanius68Jean Théberge69https://orcid.org/0000-0001-7578-4469Maria Densmore70Richard W.J. Neufeld71Chadi G. Abdallah72https://orcid.org/0000-0001-5783-6181Christopher L. Averill73https://orcid.org/0000-0001-7575-6142Ilan Harpaz-Rotem74Ifat Levy75John H. Krystal76https://orcid.org/0000-0001-6952-1726Elbert Geuze77https://orcid.org/0000-0003-3479-2379Remko van Lutterveld78https://orcid.org/0000-0003-1844-0584Emily L. Dennis79https://orcid.org/0000-0001-7112-4009David F. Tate80David X. Cifu81William C. Walker82https://orcid.org/0000-0001-5813-3939Elisabeth A. Wilde83Nic J.A. van der Wee84https://orcid.org/0000-0003-3235-1633Robert R.J.M. Vermeiren85Steven J.A. van der Werff86Katie McLaughlin87Kelly Sambrook88Matthew Peverill89Joaquim Radua90Lauren E. Salminen91Neda Jahanshad92Sophia I. Thomopoulos93Anthony James94Lucia Valmaggia95https://orcid.org/0000-0001-6099-8464Paul M. Thompson96Rajendra A. Morey97Matthew J. Kempton98https://orcid.org/0000-0003-3541-9947Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UKDepartment of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UKBrain Imaging and Analysis Center, Duke University, Durham, NC, USA Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USABrain Imaging and Analysis Center, Duke University, Durham, NC, USA Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USABrain Imaging and Analysis Center, Duke University, Durham, NC, USA Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USADepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands ARQ National Psychotrauma Centre, Diemen, The NetherlandsDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The NetherlandsDe Viersprong Mental Health Specialist in Personality Disorders, Family and Behavior, Amsterdam, The NetherlandsDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Clinical Psychology, Utrecht University, Utrecht, The NetherlandsDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Donders Center for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The NetherlandsDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Institute of Psychology, Clinical Psychology, Leiden University, Leiden, The NetherlandsLaboratory 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, ChinaLaboratory 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, ChinaLaboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Center for Global Health Equity, New York University Shanghai, Shanghai, ChinaDepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USADepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USADepartment of Neuroscience, University of Rochester Medical Center, Rochester, NY, USADepartment of Psychology, University of Haifa, Haifa, IsraelDepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, IsraelDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USADepartment of Psychiatry, Harvard Medical School, Boston, MA, USA Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USADivision of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USADepartment of Psychiatry, Harvard Medical School, Boston, MA, USA Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USADepartment of Psychiatry, Harvard Medical School, Boston, MA, USA Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USADepartment of Psychiatry, Harvard Medical School, Boston, MA, USA Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USAMinneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USAMinneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USAMinneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA VA Palo Alto Health Care System, Palo Alto, CA, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA, USADepartment of Psychiatry, Neuroimaging Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USASouth African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South AfricaSouth African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South AfricaSouth African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South AfricaDepartment of Psychiatry, Stellenbosch University, Stellenbosch, South Africa South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South AfricaDepartment of Psychiatry, Stellenbosch University, Stellenbosch, South Africa South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South AfricaDepartment of Psychiatry, Stellenbosch University, Stellenbosch, South Africa South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South AfricaDepartment of Psychology, University of Minnesota, Minneapolis, MN, USADepartment of Psychology, University of Minnesota, Minneapolis, MN, USAInstitute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, GermanyInstitute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, GermanyDivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA Sioux Falls VA Health Care System, Sioux Falls, SD, USADivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New ZealandCenter for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA Department of Psychology, University of South Dakota, Vermillion, SD, USA Disaster Mental Health Institute, University of South Dakota, Vermillion, SD, USASioux Falls VA Health Care System, Sioux Falls, SD, USA Department of Psychology, University of South Dakota, Vermillion, SD, USADepartments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USADivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA Sioux Falls VA Health Care System, Sioux Falls, SD, USA Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USADepartment of Psychiatry, University of Toledo, Toledo, OH, USADepartment of Psychiatry, University of Toledo, Toledo, OH, USADepartment of Psychiatry, University of Toledo, Toledo, OH, USADepartment of Neurosciences, University of Toledo, Toledo, OH, USACenter for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USADepartment of Psychiatry, University of Wisconsin-Madison, Madison, WI, USACenter 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, USADepartment of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USADivision of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USAComprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USA Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin Milwaukee, Milwaukee, WI, USADepartment of Psychology, Marquette University, Milwaukee, WI, USAMunroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Psychology, Vanderbilt University, Nashville, TN, USADepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USAVeterans 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, USAMasonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USADepartment of Neuroscience, Western University, London, ON, CanadaDepartments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, CanadaDepartments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, CanadaDepartments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, CanadaDepartment of Psychiatry, Baylor College of Medicine, Houston, TX, USA Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USADepartment of Psychiatry, Baylor College of Medicine, Houston, TX, USADivision of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA Departments of Psychiatry and of Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USADivision of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USADepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USAMinistry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands Brain Research and Innovation Centre, University Medical Center, Utrecht, The NetherlandsMinistry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands Brain Research and Innovation Centre, University Medical Center, Utrecht, The NetherlandsDepartment of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA Department of Radiology, Stanford University, Stanford, CA, USADepartment of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USADepartment of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USADepartment of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA Richmond VAMC, Central Virginia VA Health Care System, Richmond, VA, USADepartment of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USADepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands Leiden Institute for Brain and Cognition, Leiden University, Leiden, The NetherlandsDepartment of Psychiatry, Leiden University Medical Center, Leiden, The NetherlandsInstitute of Psychology, Clinical Psychology, Leiden University, Leiden, The Netherlands Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands Leiden Institute for Brain and Cognition, Leiden University, Leiden, The NetherlandsDepartment of Psychology, Harvard University, Cambridge, MA, USADepartment of Radiology, University of Washington, Seattle, WA, USADepartment of Psychology, University of Washington, Seattle, WA, USAInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, University of Barcelona, Barcelona, SpainImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USAImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USAImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USADepartment of Psychiatry, University of Oxford, Oxford, UK Highfield Unit, Warneford Hospital, Oxford, UKCentre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Department of Psychiatry, KU Leuven, Leuven, BelgiumImaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USABrain Imaging and Analysis Center, Duke University, Durham, NC, USA Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USADepartment of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Abstract Background Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. Methods T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). Results PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected = .001). Conclusions PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology. https://www.cambridge.org/core/product/identifier/S092493382510062X/type/journal_articlebrain structuregray matter volumeneuroimagingPTSDtraumavoxel-based morphometry |
| spellingShingle | Cheryl R.Z. See Shuqing Si C. Lexi Baird Courtney C. Haswell Ahmed Hussain Miranda Olff Dick J. Veltman Jessie L. Frijling Mirjam van Zuiden Saskia B.J. Koch Laura Nawijn Li Wang Ye Zhu Gen Li Yuval Neria Xi Zhu Benjamin Suarez-Jimenez Sigal Zilcha-Mano Amit Lazarov Jennifer S. Stevens Kerry Ressler Negar Fani Tanja Jovanovic Sanne J.H. van Rooij Milissa L. Kaufman Lauren A.M. Lebois Isabelle M. Rosso Elizabeth A. Olson Justin T. Baker Scott R. Sponheim Seth G. Disner Nicholas D. Davenport Amit Etkin Adi Maron-Katz Murray B. Stein Martha E. Shenton Dan J. Stein Jonathan Ipser Sheri-Michelle Koopowitz Soraya Seedat Stefan du Plessis Leigh L. van den Heuvel Shmuel Lissek Hannah Berg Thomas Straube David Hofman Lee A. Baugh Gina L. Forster Raluca M. Simons Jeffrey S. Simons Vincent A. Magnotta Kelene A. Fercho Xin Wang Andrew S. Cotton Erin N. O’Leary Hong Xie Daniel W. Grupe Jack B. Nitschke Richard J. Davidson Christine L. Larson Terri A. deRoon-Cassini Carissa W. Tomas Jacklynn M. Fitzgerald Jennifer Urbano Blackford Bunmi O. Olatunji Evan M. Gordon Geoffrey May Steven M. Nelson Ruth Lanius Jean Théberge Maria Densmore Richard W.J. Neufeld Chadi G. Abdallah Christopher L. Averill Ilan Harpaz-Rotem Ifat Levy John H. Krystal Elbert Geuze Remko van Lutterveld Emily L. Dennis David F. Tate David X. Cifu William C. Walker Elisabeth A. Wilde Nic J.A. van der Wee Robert R.J.M. Vermeiren Steven J.A. van der Werff Katie McLaughlin Kelly Sambrook Matthew Peverill Joaquim Radua Lauren E. Salminen Neda Jahanshad Sophia I. Thomopoulos Anthony James Lucia Valmaggia Paul M. Thompson Rajendra A. Morey Matthew J. Kempton A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study European Psychiatry brain structure gray matter volume neuroimaging PTSD trauma voxel-based morphometry |
| title | A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study |
| title_full | A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study |
| title_fullStr | A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study |
| title_full_unstemmed | A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study |
| title_short | A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study |
| title_sort | whole brain voxel based analysis of structural abnormalities in ptsd an enigma pgc study |
| topic | brain structure gray matter volume neuroimaging PTSD trauma voxel-based morphometry |
| url | https://www.cambridge.org/core/product/identifier/S092493382510062X/type/journal_article |
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