A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

doi:10.1192/j.eurpsy.2025.10062

Review

. 2025 Jul 22;68(1):e97.

doi: 10.1192/j.eurpsy.2025.10062.

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

Cheryl R Z See¹, Shuqing Si¹, C Lexi Baird^{2

3}, Courtney C Haswell^{2

3}, Ahmed Hussain^{2

3}, Miranda Olff^{4

5}, Dick J Veltman⁴, Jessie L Frijling⁶, Mirjam van Zuiden^{4

7}, Saskia B J Koch^{4

8}, Laura Nawijn^{4

9}, Li Wang^{10

11}, Ye Zhu^{10

11}, Gen Li^{10

12}, Yuval Neria^{13

14}, Xi Zhu^{13

14}, Benjamin Suarez-Jimenez¹⁵, Sigal Zilcha-Mano¹⁶, Amit Lazarov^{13

17}, Jennifer S Stevens¹⁸, Kerry Ressler^{18

19

20}, Negar Fani¹⁸, Tanja Jovanovic^{18

21}, Sanne J H van Rooij¹⁸, Milissa L Kaufman^{20

22}, Lauren A M Lebois^{19

20}, Isabelle M Rosso^{20

23}, Elizabeth A Olson^{20

23}, Justin T Baker^{20

24}, Scott R Sponheim^{25

26}, Seth G Disner^{25

26}, Nicholas D Davenport^{25

26}, Amit Etkin^{27

28}, Adi Maron-Katz²⁷, Murray B Stein²⁹, Martha E Shenton^{30

31

32}, Dan J Stein³³, Jonathan Ipser³³, Sheri-Michelle Koopowitz³³, Soraya Seedat^{34

35}, Stefan du Plessis^{34

35}, Leigh L van den Heuvel^{34

35}, Shmuel Lissek³⁶, Hannah Berg³⁶, Thomas Straube³⁷, David Hofman³⁷, Lee A Baugh^{38

39

40}, Gina L Forster^{38

39

41}, Raluca M Simons^{39

42

43}, Jeffrey S Simons^{40

42}, Vincent A Magnotta⁴⁴, Kelene A Fercho^{38

39

40

45}, Xin Wang⁴⁶, Andrew S Cotton⁴⁶, Erin N O'Leary⁴⁶, Hong Xie⁴⁷, Daniel W Grupe⁴⁸, Jack B Nitschke⁴⁹, Richard J Davidson^{48

49

50}, Christine L Larson⁵¹, Terri A deRoon-Cassini^{52

53}, Carissa W Tomas^{53

54}, Jacklynn M Fitzgerald⁵⁵, Jennifer Urbano Blackford^{56

57}, Bunmi O Olatunji⁵⁸, Evan M Gordon⁵⁹, Geoffrey May^{60

61

62

63}, Steven M Nelson^{64

65}, Ruth Lanius⁶⁶, Jean Théberge⁶⁷, Maria Densmore⁶⁷, Richard W J Neufeld⁶⁷, Chadi G Abdallah^{68

69}, Christopher L Averill⁶⁸, Ilan Harpaz-Rotem^{70

71}, Ifat Levy^{70

72}, John H Krystal^{69

70}, Elbert Geuze^{73

74}, Remko van Lutterveld^{73

74}, Emily L Dennis^{75

76

77

78}, David F Tate^{75

76}, David X Cifu⁷⁹, William C Walker^{79

80}, Elisabeth A Wilde^{75

76

81}, Nic J A van der Wee^{82

83}, Robert R J M Vermeiren⁸², Steven J A van der Werff^{9

82

83}, Katie McLaughlin⁸⁴, Kelly Sambrook⁸⁵, Matthew Peverill⁸⁶, Joaquim Radua⁸⁷, Lauren E Salminen⁷⁷, Neda Jahanshad⁷⁷, Sophia I Thomopoulos⁷⁷, Anthony James^{88

89}, Lucia Valmaggia^{90

91

92}, Paul M Thompson⁷⁷, Rajendra A Morey^{2

3}, Matthew J Kempton¹

Affiliations

¹ Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
³ Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁴ Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁵ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
⁶ De Viersprong Mental Health Specialist in Personality Disorders, Family and Behavior, Amsterdam, The Netherlands.
⁷ Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
⁸ Donders Center for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
⁹ Institute of Psychology, Clinical Psychology, Leiden University, Leiden, The Netherlands.
¹⁰ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹¹ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹² Center for Global Health Equity, New York University Shanghai, Shanghai, China.
¹³ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
¹⁴ Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
¹⁵ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
¹⁶ Department of Psychology, University of Haifa, Haifa, Israel.
¹⁷ School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel.
¹⁸ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
¹⁹ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁰ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²¹ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²² Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA.
²³ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA.
²⁴ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
²⁵ Minneapolis VA Health Care System, Minneapolis, MN, USA.
²⁶ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
²⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
²⁸ VA Palo Alto Health Care System, Palo Alto, CA, USA.
²⁹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
³⁰ Department of Psychiatry, Neuroimaging Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³¹ Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
³² Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³³ 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.
³⁴ Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
³⁵ South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
³⁶ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
³⁷ Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
³⁸ Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
³⁹ Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA.
⁴⁰ Sioux Falls VA Health Care System, Sioux Falls, SD, USA.
⁴¹ Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand.
⁴² Department of Psychology, University of South Dakota, Vermillion, SD, USA.
⁴³ Disaster Mental Health Institute, University of South Dakota, Vermillion, SD, USA.
⁴⁴ Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
⁴⁵ Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA.
⁴⁶ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁴⁷ Department of Neurosciences, University of Toledo, Toledo, OH, USA.
⁴⁸ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁴⁹ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁰ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵¹ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
⁵² Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵³ Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵⁴ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin Milwaukee, Milwaukee, WI, USA.
⁵⁵ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁵⁶ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
⁵⁷ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁸ Department of Psychology, Vanderbilt University, Nashville, TN, USA.
⁵⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁶⁰ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁶¹ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁶² Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁶³ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁶⁴ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
⁶⁵ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁶⁶ Department of Neuroscience, Western University, London, ON, Canada.
⁶⁷ Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada.
⁶⁸ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁶⁹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁷⁰ Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA.
⁷¹ Departments of Psychiatry and of Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁷² Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁷³ Ministry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands.
⁷⁴ Brain Research and Innovation Centre, University Medical Center, Utrecht, The Netherlands.
⁷⁵ Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁷⁶ George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
⁷⁷ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
⁷⁸ Department of Radiology, Stanford University, Stanford, CA, USA.
⁷⁹ Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA.
⁸⁰ Richmond VAMC, Central Virginia VA Health Care System, Richmond, VA, USA.
⁸¹ H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
⁸² Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁸³ Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
⁸⁴ Department of Psychology, Harvard University, Cambridge, MA, USA.
⁸⁵ Department of Radiology, University of Washington, Seattle, WA, USA.
⁸⁶ Department of Psychology, University of Washington, Seattle, WA, USA.
⁸⁷ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, University of Barcelona, Barcelona, Spain.
⁸⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
⁸⁹ Highfield Unit, Warneford Hospital, Oxford, UK.
⁹⁰ Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
⁹¹ Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁹² Department of Psychiatry, KU Leuven, Leuven, Belgium.

PMID: 40692500
PMCID: PMC12344465
DOI: 10.1192/j.eurpsy.2025.10062

Review

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

Cheryl R Z See et al. Eur Psychiatry. 2025.

. 2025 Jul 22;68(1):e97.

doi: 10.1192/j.eurpsy.2025.10062.

Authors

Affiliations

¹ Department of Psychosis, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
³ Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁴ Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁵ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
⁶ De Viersprong Mental Health Specialist in Personality Disorders, Family and Behavior, Amsterdam, The Netherlands.
⁷ Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
⁸ Donders Center for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
⁹ Institute of Psychology, Clinical Psychology, Leiden University, Leiden, The Netherlands.
¹⁰ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹¹ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹² Center for Global Health Equity, New York University Shanghai, Shanghai, China.
¹³ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
¹⁴ Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
¹⁵ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
¹⁶ Department of Psychology, University of Haifa, Haifa, Israel.
¹⁷ School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel.
¹⁸ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
¹⁹ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁰ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²¹ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²² Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA.
²³ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA.
²⁴ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
²⁵ Minneapolis VA Health Care System, Minneapolis, MN, USA.
²⁶ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
²⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
²⁸ VA Palo Alto Health Care System, Palo Alto, CA, USA.
²⁹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
³⁰ Department of Psychiatry, Neuroimaging Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³¹ Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
³² Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³³ 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.
³⁴ Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
³⁵ South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
³⁶ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
³⁷ Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
³⁸ Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
³⁹ Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA.
⁴⁰ Sioux Falls VA Health Care System, Sioux Falls, SD, USA.
⁴¹ Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand.
⁴² Department of Psychology, University of South Dakota, Vermillion, SD, USA.
⁴³ Disaster Mental Health Institute, University of South Dakota, Vermillion, SD, USA.
⁴⁴ Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
⁴⁵ Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA.
⁴⁶ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁴⁷ Department of Neurosciences, University of Toledo, Toledo, OH, USA.
⁴⁸ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁴⁹ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁰ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵¹ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
⁵² Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵³ Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵⁴ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin Milwaukee, Milwaukee, WI, USA.
⁵⁵ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁵⁶ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
⁵⁷ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁸ Department of Psychology, Vanderbilt University, Nashville, TN, USA.
⁵⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁶⁰ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁶¹ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁶² Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁶³ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁶⁴ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
⁶⁵ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁶⁶ Department of Neuroscience, Western University, London, ON, Canada.
⁶⁷ Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada.
⁶⁸ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁶⁹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁷⁰ Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA.
⁷¹ Departments of Psychiatry and of Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁷² Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁷³ Ministry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands.
⁷⁴ Brain Research and Innovation Centre, University Medical Center, Utrecht, The Netherlands.
⁷⁵ Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁷⁶ George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
⁷⁷ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
⁷⁸ Department of Radiology, Stanford University, Stanford, CA, USA.
⁷⁹ Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA.
⁸⁰ Richmond VAMC, Central Virginia VA Health Care System, Richmond, VA, USA.
⁸¹ H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
⁸² Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁸³ Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
⁸⁴ Department of Psychology, Harvard University, Cambridge, MA, USA.
⁸⁵ Department of Radiology, University of Washington, Seattle, WA, USA.
⁸⁶ Department of Psychology, University of Washington, Seattle, WA, USA.
⁸⁷ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, University of Barcelona, Barcelona, Spain.
⁸⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
⁸⁹ Highfield Unit, Warneford Hospital, Oxford, UK.
⁹⁰ Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
⁹¹ Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁹² Department of Psychiatry, KU Leuven, Leuven, Belgium.

PMID: 40692500
PMCID: PMC12344465
DOI: 10.1192/j.eurpsy.2025.10062

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, p_corrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, p_corrected = .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: PTSD; brain structure; gray matter volume; neuroimaging; trauma; voxel-based morphometry.

PubMed Disclaimer

Conflict of interest statement

N Jahanshad received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the content of this article. P Thompson received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the topic of this manuscript. R Davidson is the founder and president of, and serves on the board of directors for, the non-profit organization Healthy Minds Innovations, Inc. L 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, and spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals unrelated to the present work. ISSTD and NIMH were not involved in the analysis or preparation of the manuscript. C Abdullah has served as a consultant, speaker and/or on advisory boards for Douglas Pharmaceuticals, Freedom Biosciences, FSV7, Lundbeck, Psilocybin Labs, Genentech, Janssen and Aptinyx; served as editor of Chronic Stress for Sage Publications, Inc; and filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). J Krystal is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Biomedisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; is a stockholder in Biohaven Pharmaceuticals; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, US Patent No. 5,447,948 (issued September 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued July 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014). Filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). S Nelson consults for Turing Medical, which commercializes FIRMM. This interest has been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. E Olson is employed by the nonprofit organization Crisis Text Line, for work unrelated to the content of this manuscript. All other authors report no potential competing interests or disclosures.

Figures

**Figure 1.**
Patients with PTSD exhibited lower regional gray matter volume compared to controls throughout the brain as seen in the orange highlighted regions in the figure, with a peak effect in the left cerebellum [−4,−72,-10] (see also Supplementary Table S6).

**Figure 2.**
The blue highlighted regions represent smaller gray matter volumes associated with: (A) higher PTSD severity scores, with the peak effect in the right cerebellum [4,−48,−58]; and (B) higher depression severity scores, with the peak effect in the right superior frontal gyrus [14, 66, 6] (see also Supplementary Tables S12 and S13).

See this image and copyright information in PMC

References

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[1] Benjet C, Bromet E, Karam EG, Kessler RC, McLaughlin KA, Ruscio AM, et al. The epidemiology of traumatic event exposure worldwide: Results from the world mental health survey consortium. Psychol Med. 2016;46(2):327–43. 10.1017/S0033291715001981. - DOI - PMC - PubMed

[2] Benjet C, Bromet E, Karam EG, Kessler RC, McLaughlin KA, Ruscio AM, et al. The epidemiology of traumatic event exposure worldwide: Results from the world mental health survey consortium. Psychol Med. 2016;46(2):327–43. 10.1017/S0033291715001981. - DOI - PMC - PubMed

[3] Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26(5):537–47. 10.1002/jts.21848. - DOI - PMC - PubMed

[4] Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26(5):537–47. 10.1002/jts.21848. - DOI - PMC - PubMed

[5] Association AP. Diagnostic and statistical manual of mental disorders. 5th ed. American Psychiatric Association; 2013.

[6] Association AP. Diagnostic and statistical manual of mental disorders. 5th ed. American Psychiatric Association; 2013.

[7] Bromis K, Calem M, Reinders A, Williams SCR, Kempton MJ. Meta-analysis of 89 structural MRI studies in posttraumatic stress disorder and comparison with major depressive disorder. Am J Psychiatry. 2018;175(10):989–98. 10.1176/appi.ajp.2018.17111199. - DOI - PMC - PubMed

[8] Bromis K, Calem M, Reinders A, Williams SCR, Kempton MJ. Meta-analysis of 89 structural MRI studies in posttraumatic stress disorder and comparison with major depressive disorder. Am J Psychiatry. 2018;175(10):989–98. 10.1176/appi.ajp.2018.17111199. - DOI - PMC - PubMed

[9] Siehl S, Zohair R, Guldner S, Nees F. Gray matter differences in adults and children with posttraumatic stress disorder: A systematic review and meta-analysis of 113 studies and 11 meta-analyses. J Affect Disord. 2023;333:489–516. 10.1016/j.jad.2023.04.028. - DOI - PubMed

[10] Siehl S, Zohair R, Guldner S, Nees F. Gray matter differences in adults and children with posttraumatic stress disorder: A systematic review and meta-analysis of 113 studies and 11 meta-analyses. J Affect Disord. 2023;333:489–516. 10.1016/j.jad.2023.04.028. - DOI - PubMed

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A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

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A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

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