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

Journal: Molecular Psychiatry
Published:
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.

Authors
Ashley Huggins, C Baird, Melvin Briggs, Sarah Laskowitz, Ahmed Hussain, Samar Fouda, Courtney Haswell, Delin Sun, Lauren Salminen, Neda Jahanshad, Sophia Thomopoulos, Dick Veltman, Jessie Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B Koch, Laura Nawjin, Li Wang, Ye Zhu, Gen Li, Dan Stein, Jonathan Ipser, Soraya Seedat, Stefan Du Plessis, Leigh Van Den Heuvel, Benjamin Suarez Jimenez, Xi Zhu, Yoojean Kim, Xiaofu He, Sigal Zilcha Mano, Amit Lazarov, Yuval Neria, Jennifer Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J Van Rooij, Negar Fani, Anna Hudson, Sven Mueller, Anika Sierk, Antje Manthey, Henrik Walter, Judith Daniels, Christian Schmahl, Julia Herzog, Pavel Říha, Ivan Rektor, Lauren A Lebois, Milissa Kaufman, Elizabeth Olson, Justin Baker, Isabelle Rosso, Anthony King, Isreal Liberzon, Mike Angstadt, Nicholas Davenport, Scott Sponheim, Seth Disner, Thomas Straube, David Hofmann, Rongfeng Qi, Guang Lu, Lee Baugh, Gina Forster, Raluca Simons, Jeffrey Simons, Vincent Magnotta, Kelene Fercho, Adi Maron Katz, Amit Etkin, Andrew Cotton, Erin O'leary, Hong Xie, Xin Wang, Yann Quidé, Wissam El Hage, Shmuel Lissek, Hannah Berg, Steven Bruce, Josh Cisler, Marisa Ross, Ryan Herringa, Daniel Grupe, Jack Nitschke, Richard Davidson, Christine Larson, Terri Deroon Cassini, Carissa Tomas, Jacklynn Fitzgerald, Jennifer Blackford, Bunmi Olatunji, William Kremen, Michael Lyons, Carol Franz, Evan Gordon, Geoffrey May, Steven Nelson, Chadi Abdallah, Ifat Levy, Ilan Harpaz Rotem, John Krystal, Emily Dennis, David Tate, David Cifu, William Walker, Elizabeth Wilde, Ian Harding, Rebecca Kerestes, Paul Thompson, Rajendra Morey