Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Ashley A Huggins^{1

2}, C Lexi Baird^{3

4}, Melvin Briggs^{3

4}, Sarah Laskowitz^{3

4}, Ahmed Hussain^{3

4}, Samar Fouda^{3

4

5}, Courtney Haswell^{3

4}, Delin Sun^{3

4

6}, Lauren E Salminen⁷, Neda Jahanshad⁷, Sophia I Thomopoulos⁷, Dick J Veltman⁸, Jessie L Frijling^{9

10}, Miranda Olff^{9

11}, Mirjam van Zuiden⁹, Saskia B J Koch^{9

12}, Laura Nawjin^{8

9}, Li Wang^{13

14}, Ye Zhu^{13

14}, Gen Li^{13

15}, Dan J Stein¹⁶, Jonathan Ipser¹⁶, Soraya Seedat^{17

18}, Stefan du Plessis^{17

18}, Leigh L van den Heuvel^{17

18}, Benjamin Suarez-Jimenez¹⁹, Xi Zhu^{20

21}, Yoojean Kim²¹, Xiaofu He^{20

21}, Sigal Zilcha-Mano²², Amit Lazarov^{20

23}, Yuval Neria^{20

21}, Jennifer S Stevens²⁴, Kerry J Ressler^{24

25

26}, Tanja Jovanovic^{24

27}, Sanne J H van Rooij²⁴, Negar Fani²⁴, Anna R Hudson²⁸, Sven C Mueller²⁸, Anika Sierk²⁹, Antje Manthey²⁹, Henrik Walter²⁹, Judith K Daniels³⁰, Christian Schmahl³¹, Julia I Herzog³¹, Pavel Říha^{32

33}, Ivan Rektor³³, Lauren A M Lebois^{26

34}, Milissa L Kaufman^{26

35}, Elizabeth A Olson^{26

34}, Justin T Baker^{26

36}, Isabelle M Rosso^{26

34}, Anthony P King³⁷, Isreal Liberzon³⁸, Mike Angstadt³⁹, Nicholas D Davenport^{40

41}, Scott R Sponheim^{40

41}, Seth G Disner^{40

41}, Thomas Straube⁴², David Hofmann⁴², Rongfeng Qi⁴³, Guang Ming Lu⁴³, Lee A Baugh^{44

45

46}, Gina L Forster^{44

45

47}, Raluca M Simons^{45

48

49}, Jeffrey S Simons^{46

48}, Vincent A Magnotta⁵⁰, Kelene A Fercho^{44

45

46

51}, Adi Maron-Katz⁵², Amit Etkin^{52

53}, Andrew S Cotton⁵⁴, Erin N O'Leary⁵⁴, Hong Xie⁵⁵, Xin Wang⁵⁴, Yann Quidé^{56

57}, Wissam El-Hage^{58

59}, Shmuel Lissek⁶⁰, Hannah Berg⁶⁰, Steven Bruce⁶¹, Josh Cisler⁶², Marisa Ross⁶³, Ryan J Herringa⁶⁴, Daniel W Grupe⁶⁵, Jack B Nitschke⁶⁶, Richard J Davidson^{65

66

67}, Christine L Larson⁶⁸, Terri A deRoon-Cassini^{69

70}, Carissa W Tomas^{70

71}, Jacklynn M Fitzgerald⁷², Jennifer Urbano Blackford^{73

74}, Bunmi O Olatunji⁷⁵, William S Kremen^{76

77}, Michael J Lyons⁷⁸, Carol E Franz^{76

77}, Evan M Gordon⁷⁹, Geoffrey May^{80

81

82

83}, Steven M Nelson^{84

85}, Chadi G Abdallah^{86

87}, Ifat Levy^{88

89}, Ilan Harpaz-Rotem^{89

90}, John H Krystal^{87

89}, Emily L Dennis^{91

92}, David F Tate^{91

92}, David X Cifu⁹³, William C Walker^{93

94}, Elizabeth A Wilde^{91

92

95}, Ian H Harding^{96

97}, Rebecca Kerestes⁹⁶, Paul M Thompson⁷, Rajendra Morey^{3

4}

Affiliations

¹ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. aahuggins@arizona.edu.
² Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA. aahuggins@arizona.edu.
³ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
⁴ Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁵ Department of Psychiatry & Behavioral Sciences, Duke School of Medicine, Durham, NC, USA.
⁶ Department of Psychology, The Education University of Hong Kong, Ting Kok, Hong Kong.
⁷ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁸ Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
⁹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹⁰ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
¹² Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹³ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹⁴ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁵ Center for Global Health Equity, New York University Shanghai, Shanghai, China.
¹⁶ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁷ Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
¹⁸ South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
¹⁹ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
²⁰ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
²¹ New York State Psychiatric Institute, New York, NY, USA.
²² University of Haifa, Haifa, Israel.
²³ Tel-Aviv University, Tel Aviv-Yafo, Israel.
²⁴ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁵ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²⁷ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²⁸ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁹ University Medical Centre Charité, Berlin, Germany.
³⁰ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
³¹ Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
³² First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
³³ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
³⁴ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁵ Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA.
³⁶ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
³⁷ Department of Psychiatry and Behavioral Health, Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA.
³⁸ Department of Psychiatry, Texas A&M University, Bryan, Texas, USA.
³⁹ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁴⁰ Minneapolis VA Health Care System, Minneapolis, MN, USA.
⁴¹ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
⁴² Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
⁴³ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
⁴⁴ Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
⁴⁵ Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA.
⁴⁶ Sioux Falls VA Health Care System, Sioux Falls, SD, USA.
⁴⁷ Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand.
⁴⁸ Department of Psychology, University of South Dakota, Vermillion, SD, USA.
⁴⁹ Disaster Mental Health Institute, Vermillion, SD, USA.
⁵⁰ Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
⁵¹ Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA.
⁵² Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁵³ VA Palo Alto Health Care System, Palo Alto, CA, USA.
⁵⁴ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁵⁵ Department of Neurosciences, University of Toledo, Toledo, OH, USA.
⁵⁶ School of Psychology, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia.
⁵⁷ Neuroscience Research Australia, Randwick, NSW, Australia.
⁵⁸ UMR1253, Université de Tours, Inserm, Tours, France.
⁵⁹ CIC1415, CHRU de Tours, Inserm, Tours, France.
⁶⁰ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁶¹ Department of Psychological Sciences, Center for Trauma Recovery University of Missouri-St. Louis, St. Louis, MO, USA.
⁶² Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁶³ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁶⁴ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁶⁵ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁶ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁷ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁸ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
⁶⁹ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷⁰ Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷¹ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin Milwaukee, Milwaukee, WI, USA.
⁷² Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁷³ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
⁷⁴ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷⁵ Department of Psychology, Vanderbilt University, Nashville, TN, USA.
⁷⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁷⁷ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
⁷⁸ Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
⁷⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁸⁰ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁸¹ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁸² Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁸³ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁸⁴ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁸⁵ Masonic Institute for the Developing Brain, Minneapolis, MN, USA.
⁸⁶ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁸⁷ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁸⁸ Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁸⁹ Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA.
⁹⁰ Departments of Psychiatry and of Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁹¹ Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁹² George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
⁹³ Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA.
⁹⁴ Veterans Affairs (VA) Richmond Health Care, Richmond, VA, USA.
⁹⁵ H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
⁹⁶ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Vic, Australia.
⁹⁷ Monash Biomedical Imaging, Monash University, Melbourne, Vic, Australia.

PMID: 38195980
PMCID: PMC11153161
DOI: 10.1038/s41380-023-02352-0

Meta-Analysis

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Ashley A Huggins et al. Mol Psychiatry. 2024 Mar.

. 2024 Mar;29(3):611-623.

doi: 10.1038/s41380-023-02352-0. Epub 2024 Jan 10.

Authors

Affiliations

¹ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. aahuggins@arizona.edu.
² Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA. aahuggins@arizona.edu.
³ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
⁴ Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
⁵ Department of Psychiatry & Behavioral Sciences, Duke School of Medicine, Durham, NC, USA.
⁶ Department of Psychology, The Education University of Hong Kong, Ting Kok, Hong Kong.
⁷ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁸ Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
⁹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹⁰ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
¹² Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹³ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹⁴ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁵ Center for Global Health Equity, New York University Shanghai, Shanghai, China.
¹⁶ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁷ Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
¹⁸ South African Medical Research Council Unit on the Genomics of Brain Disorders (GBD), Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
¹⁹ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
²⁰ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
²¹ New York State Psychiatric Institute, New York, NY, USA.
²² University of Haifa, Haifa, Israel.
²³ Tel-Aviv University, Tel Aviv-Yafo, Israel.
²⁴ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁵ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²⁷ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²⁸ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁹ University Medical Centre Charité, Berlin, Germany.
³⁰ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
³¹ Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
³² First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
³³ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
³⁴ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
³⁵ Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA.
³⁶ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
³⁷ Department of Psychiatry and Behavioral Health, Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA.
³⁸ Department of Psychiatry, Texas A&M University, Bryan, Texas, USA.
³⁹ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁴⁰ Minneapolis VA Health Care System, Minneapolis, MN, USA.
⁴¹ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
⁴² Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
⁴³ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
⁴⁴ Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
⁴⁵ Center for Brain and Behavior Research, University of South Dakota, Vermillion, SD, USA.
⁴⁶ Sioux Falls VA Health Care System, Sioux Falls, SD, USA.
⁴⁷ Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand.
⁴⁸ Department of Psychology, University of South Dakota, Vermillion, SD, USA.
⁴⁹ Disaster Mental Health Institute, Vermillion, SD, USA.
⁵⁰ Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
⁵¹ Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA.
⁵² Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁵³ VA Palo Alto Health Care System, Palo Alto, CA, USA.
⁵⁴ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁵⁵ Department of Neurosciences, University of Toledo, Toledo, OH, USA.
⁵⁶ School of Psychology, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia.
⁵⁷ Neuroscience Research Australia, Randwick, NSW, Australia.
⁵⁸ UMR1253, Université de Tours, Inserm, Tours, France.
⁵⁹ CIC1415, CHRU de Tours, Inserm, Tours, France.
⁶⁰ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁶¹ Department of Psychological Sciences, Center for Trauma Recovery University of Missouri-St. Louis, St. Louis, MO, USA.
⁶² Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁶³ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁶⁴ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁶⁵ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁶ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁷ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁶⁸ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
⁶⁹ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷⁰ Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷¹ Division of Epidemiology and Social Sciences, Institute of Health and Equity, Medical College of Wisconsin Milwaukee, Milwaukee, WI, USA.
⁷² Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁷³ Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
⁷⁴ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷⁵ Department of Psychology, Vanderbilt University, Nashville, TN, USA.
⁷⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁷⁷ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
⁷⁸ Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
⁷⁹ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁸⁰ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁸¹ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁸² Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁸³ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁸⁴ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁸⁵ Masonic Institute for the Developing Brain, Minneapolis, MN, USA.
⁸⁶ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁸⁷ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁸⁸ Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁸⁹ Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA.
⁹⁰ Departments of Psychiatry and of Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA.
⁹¹ Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁹² George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
⁹³ Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA.
⁹⁴ Veterans Affairs (VA) Richmond Health Care, Richmond, VA, USA.
⁹⁵ H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
⁹⁶ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Vic, Australia.
⁹⁷ Monash Biomedical Imaging, Monash University, Melbourne, Vic, Australia.

PMID: 38195980
PMCID: PMC11153161
DOI: 10.1038/s41380-023-02352-0

Abstract

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p_-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

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Conflict of interest statement

NJ received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the content of this manuscript. PMT received partial research support from Biogen, Inc. (Boston, USA) for research unrelated to the topic of this manuscript. CS is consultant for Boehringer Ingelheim International GmbH. LAML 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. WEH is affiliated with Air Liquide, Boehringer Ingelheim, CHUGAI, EISAI, Jazz Pharmaceuticals, Janssen, Lundbeck, Novartis, Otsuka, UCB but nothing related to this work. RJD is the founder and president of, and serves on the board of directors for, the non-profit organization Healthy Minds Innovations, Inc. CGA has served as a consultant, speaker and/or on advisory boards for 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). JHK 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). A version of this manuscript was uploaded to the biorxiv.org preprint server (10.1101/2022.10.13.512111).

Figures

**Fig. 1. ACAPULCO cerebellum parcellation for a representative subject.**
A three-dimensional display is presented in the upper half of the figure, along with coronal (left), sagittal (middle), and axial (right) views below. L left, R right.

**Fig. 2. Effects of PTSD diagnosis on cerebellar subregion volumes.**
Atlas-based effect size (Cohen’s d) maps and MNI-based coronal slices (top: y = −72; bottom: y = −54) of the significant between-group differences for cerebellar subregion volumes in PTSD vs. Controls. Negative effect sizes reflect smaller volumes in PTSD. Regions significant at p_-FDR < 0.05 are depicted in color, with the exception of right lobule V, where p_-FDR = 0.051 after adjustment; right lobule V was significant p_-FDR = 0.046) when examining PTSD severity instead of diagnosis. Grey-shaded subregions were non-significant. CM corpus medullary.

See this image and copyright information in PMC

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Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Affiliations

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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LinkOut - more resources

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