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

Journal: Molecular psychiatry

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Affiliated Institutions:  Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. aahuggins@arizona.edu. Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA. Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands. Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands. Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA. Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. New York State Psychiatric Institute, New York, NY, USA. University of Haifa, Haifa, Israel. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. University Medical Centre Charité, Berlin, Germany. Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands. Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic. Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Department of Psychiatry and Behavioral Health, Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA. Department of Psychiatry, Texas A&M University, Bryan, Texas, USA. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. Minneapolis VA Health Care System, Minneapolis, MN, USA. Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. 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. Departments of Radiology, Psychiatry, and Biomedical Engineering, University of Iowa, Iowa City, IA, USA. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. Department of Psychiatry, University of Toledo, Toledo, OH, USA. Department of Neurosciences, University of Toledo, Toledo, OH, USA. School of Psychology, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia. UMR, Université de Tours, Inserm, Tours, France. Department of Psychology, University of Minnesota, Minneapolis, MN, USA. Department of Psychological Sciences, Center for Trauma Recovery University of Missouri-St. Louis, St. Louis, MO, USA. Department of Psychiatry, University of Texas at Austin, Austin, TX, USA. Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA. School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA. 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-Milwaukee, Milwaukee, WI, USA. 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. Department of Psychology, Marquette University, Milwaukee, WI, USA. Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA. Department of Psychology, Vanderbilt University, Nashville, TN, USA. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA. Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. Veterans Integrated Service Network- Center of Excellence for Research on Returning War Veterans, Waco, TX, USA. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA. Departments of Comparative Medicine, Neuroscience and Psychology, Wu Tsai Institute, Yale University, New Haven, CT, USA. Division of Clinical Neuroscience, National Center for PTSD, West Haven, CT, USA. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA. Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Vic, Australia.

Abstract summary 

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 < 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.

Authors & Co-authors:  Huggins Baird Briggs Laskowitz Hussain Fouda Haswell Sun Salminen Jahanshad Thomopoulos Veltman Frijling Olff van Zuiden Koch Nawjin Wang Zhu Li Stein Ipser Seedat du Plessis van den Heuvel Suarez-Jimenez Zhu Kim He Zilcha-Mano Lazarov Neria Stevens Ressler Jovanovic van Rooij Fani Hudson Mueller Sierk Manthey Walter Daniels Schmahl Herzog Říha Rektor Lebois Kaufman Olson Baker Rosso King Liberzon Angstadt Davenport Sponheim Disner Straube Hofmann Qi Lu Baugh Forster Simons Simons Magnotta Fercho Maron-Katz Etkin Cotton O'Leary Xie Wang Quidé El-Hage Lissek Berg Bruce Cisler Ross Herringa Grupe Nitschke Davidson Larson deRoon-Cassini Tomas Fitzgerald Blackford Olatunji Kremen Lyons Franz Gordon May Nelson Abdallah Levy Harpaz-Rotem Krystal Dennis Tate Cifu Walker Wilde Harding Kerestes Thompson Morey

Study Outcome 

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Statistics
Citations :  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;26:537–47.
Authors :  110
Identifiers
Doi : 10.1038/s41380-023-02352-0
SSN : 1476-5578
Study Population
Male,Female
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Publication Country
England