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

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 (allp-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.