European Psychiatry (Jan 2025)
A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study
- 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
Affiliations
- Cheryl R.Z. See
- ORCiD
- Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- Shuqing Si
- ORCiD
- Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- C. Lexi Baird
- 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
- Courtney C. Haswell
- 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
- Ahmed Hussain
- ORCiD
- 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
- Miranda Olff
- Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands ARQ National Psychotrauma Centre, Diemen, The Netherlands
- Dick J. Veltman
- Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands
- Jessie L. Frijling
- De Viersprong Mental Health Specialist in Personality Disorders, Family and Behavior, Amsterdam, The Netherlands
- Mirjam van Zuiden
- Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Clinical Psychology, Utrecht University, Utrecht, The Netherlands
- Saskia B.J. Koch
- ORCiD
- Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Donders Center for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
- Laura Nawijn
- Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands Institute of Psychology, Clinical Psychology, Leiden University, Leiden, The Netherlands
- Li Wang
- ORCiD
- 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
- Ye Zhu
- 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
- Gen Li
- Laboratory 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, China
- Yuval Neria
- Department of Psychiatry, Columbia University Medical Center, New York, NY, USA Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA
- Xi Zhu
- Department of Psychiatry, Columbia University Medical Center, New York, NY, USA Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA
- Benjamin Suarez-Jimenez
- ORCiD
- Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA
- Sigal Zilcha-Mano
- Department of Psychology, University of Haifa, Haifa, Israel
- Amit Lazarov
- ORCiD
- Department of Psychiatry, Columbia University Medical Center, New York, NY, USA School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel
- Jennifer S. Stevens
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Kerry Ressler
- ORCiD
- Department 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, USA
- Negar Fani
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Tanja Jovanovic
- Department 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, USA
- Sanne J.H. van Rooij
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Milissa L. Kaufman
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USA
- Lauren A.M. Lebois
- ORCiD
- Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Isabelle M. Rosso
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA
- Elizabeth A. Olson
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA
- Justin T. Baker
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA
- Scott R. Sponheim
- Minneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
- Seth G. Disner
- ORCiD
- Minneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
- Nicholas D. Davenport
- Minneapolis VA Health Care System, Minneapolis, MN, USA Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
- Amit Etkin
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA VA Palo Alto Health Care System, Palo Alto, CA, USA
- Adi Maron-Katz
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
- Murray B. Stein
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Martha E. Shenton
- Department 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, USA
- Dan J. Stein
- ORCiD
- South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
- Jonathan Ipser
- South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
- Sheri-Michelle Koopowitz
- ORCiD
- South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
- Soraya Seedat
- Department 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 Africa
- Stefan du Plessis
- Department 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 Africa
- Leigh L. van den Heuvel
- Department 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 Africa
- Shmuel Lissek
- Department of Psychology, University of Minnesota, Minneapolis, MN, USA
- Hannah Berg
- Department of Psychology, University of Minnesota, Minneapolis, MN, USA
- Thomas Straube
- Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
- David Hofman
- ORCiD
- Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
- Lee A. Baugh
- ORCiD
- Division 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
- Gina L. Forster
- Division 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 Zealand
- Raluca M. Simons
- Center 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, USA
- Jeffrey S. Simons
- Sioux Falls VA Health Care System, Sioux Falls, SD, USA Department of Psychology, University of South Dakota, Vermillion, SD, USA
- Vincent A. Magnotta
- ORCiD
- Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA
- Kelene A. Fercho
- ORCiD
- Division 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, USA
- Xin Wang
- Department of Psychiatry, University of Toledo, Toledo, OH, USA
- Andrew S. Cotton
- Department of Psychiatry, University of Toledo, Toledo, OH, USA
- Erin N. O’Leary
- Department of Psychiatry, University of Toledo, Toledo, OH, USA
- Hong Xie
- Department of Neurosciences, University of Toledo, Toledo, OH, USA
- Daniel W. Grupe
- Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA
- Jack B. Nitschke
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
- Richard J. Davidson
- 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
- Christine L. Larson
- ORCiD
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
- Terri A. deRoon-Cassini
- Division 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, USA
- Carissa W. Tomas
- ORCiD
- Comprehensive 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, USA
- Jacklynn M. Fitzgerald
- Department of Psychology, Marquette University, Milwaukee, WI, USA
- Jennifer Urbano Blackford
- ORCiD
- Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
- Bunmi O. Olatunji
- Department of Psychology, Vanderbilt University, Nashville, TN, USA
- Evan M. Gordon
- Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
- Geoffrey May
- 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
- Steven M. Nelson
- Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
- Ruth Lanius
- Department of Neuroscience, Western University, London, ON, Canada
- Jean Théberge
- ORCiD
- Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada
- Maria Densmore
- Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada
- Richard W.J. Neufeld
- Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada
- Chadi G. Abdallah
- ORCiD
- Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
- Christopher L. Averill
- ORCiD
- Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA
- Ilan Harpaz-Rotem
- Division 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, USA
- Ifat Levy
- Division 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, USA
- John H. Krystal
- ORCiD
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA
- Elbert Geuze
- ORCiD
- Ministry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands Brain Research and Innovation Centre, University Medical Center, Utrecht, The Netherlands
- Remko van Lutterveld
- ORCiD
- Ministry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands Brain Research and Innovation Centre, University Medical Center, Utrecht, The Netherlands
- Emily L. Dennis
- ORCiD
- Department 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, USA
- David F. Tate
- Department 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
- David X. Cifu
- Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA
- William C. Walker
- ORCiD
- Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA Richmond VAMC, Central Virginia VA Health Care System, Richmond, VA, USA
- Elisabeth A. Wilde
- Department 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, USA
- Nic J.A. van der Wee
- ORCiD
- Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands
- Robert R.J.M. Vermeiren
- Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
- Steven J.A. van der Werff
- Institute 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 Netherlands
- Katie McLaughlin
- Department of Psychology, Harvard University, Cambridge, MA, USA
- Kelly Sambrook
- Department of Radiology, University of Washington, Seattle, WA, USA
- Matthew Peverill
- Department of Psychology, University of Washington, Seattle, WA, USA
- Joaquim Radua
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, University of Barcelona, Barcelona, Spain
- Lauren E. Salminen
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
- Neda Jahanshad
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
- Sophia I. Thomopoulos
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
- Anthony James
- Department of Psychiatry, University of Oxford, Oxford, UK Highfield Unit, Warneford Hospital, Oxford, UK
- Lucia Valmaggia
- ORCiD
- Centre 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, Belgium
- Paul M. Thompson
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
- Rajendra A. Morey
- 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
- Matthew J. Kempton
- ORCiD
- Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- DOI
- https://doi.org/10.1192/j.eurpsy.2025.10062
- Journal volume & issue
-
Vol. 68
Abstract
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.
Keywords
