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

Background: The cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions.


Methods: We quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640; Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained 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 total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate (p-FDR < .05).


Results: PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. 


Conclusions: These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-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. 

Ashley A. Huggins, C. Lexi Baird, Melvin Briggs, Sarah Laskowitz, Samar Foudra, Courtney Haswell, Delin Sun, Lauren E. Salminen, Neda Jahanshad, Sophia I. Thomopoulos, Dick J. Veltman, Jessie L. Frijling, Miranda Olff, Mirjam van Zuiden, Saskia B.J. Koch, Laura Nawjin, Li Wang, Ye Zhu, Gen Li, Dan J. Stein, Johnathan Ipser, Soraya Seedat, Stefan du Plessis, Leigh L. van den Heuvel, Benjamin Suarez-Jimenez, Xi Zhu, Yoojean Kim, Xiaofu He, Sigal Zilcha-Mano, Amit Lazarov, Yuval Neria, Jennifer S. Stevens, Kerry J. Ressler, Tanja Jovanovic, Sanne JH van Rooij, Negar Fan, Anna R. Hudson, Sven C. Mueller, Anika Sierk, Antje Manthey, Henrik Walter, Judith K. Daniels, Christian Schmahl, Julia I. Herzog, Pavel Říha, Ivan Rektor, Lauren A.M. Lebois, Milissa L. Kaufman, Elizabeth A. Olson, Justin T. Baker, Isabelle M. Rosso, Anthony P. King, Isreal Liberzon, Mike Angstadt, Nicholas D. Davenport, Scott R. Sponheim, Seth G. Disner, Thomas Straube, David Hofmann, Rongfeng Qi, Guang Ming Lu, Lee A. Baugh, Gina L. Forster, Raluca M. Simons, Jeffrey S. Simons, Vincent A. Magnotta, Kelene A. Fercho, Adi Maron-Katz, Amit Etkin, Andrew S. Cotton, Erin N. O’Leary, Hong Xie, Xin Wang, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven Bruce, Josh Cisler, Marisa Ross, Ryan J. Herringa, Daniel W. Grupe, Jack B. Nitschke, Richard J. Davidson, Christine Larson, Terri A. deRoon-Cassini, Carissa W. Tomas, Jacklynn M. Fitzgerald, Jennifer Urbano Blackford, Bunmi O. Olatunji, William S. Kremen, Michael J. Lyons, Carol E. Franz, Evan M. Gordon, Geoffrey May, Steven M. Nelson, Chadi G. Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H. Krystal, Emily L. Dennis, David F. Tate, David X. Cifu, William C. Walker, Elizabeth A. Wilde, Ian H. Harding, Rebecca Kerestes, Paul M. Thompson, Rajendra Morey | 2022
In: BioRxiv: the preprint server for biology
Adults, Cognitive Disorders, Mental health, Neurobiology, Posttraumatic Stress Disorder, Psychopathology, Psychotrauma, PTSD (en), Quality of Life, Statistical Analysis
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