Faculty Collaboration Database

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup. Mol Psychiatry 2024 Mar;29(3):611-623

Date

01/10/2024

Pubmed ID

38195980

Pubmed Central ID

PMC11153161

DOI

10.1038/s41380-023-02352-0

Scopus ID

2-s2.0-85181942750 (requires institutional sign-in at Scopus site)

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.

Author List

Huggins AA, Baird CL, Briggs M, Laskowitz S, Hussain A, Fouda S, Haswell C, Sun D, Salminen LE, Jahanshad N, Thomopoulos SI, Veltman DJ, Frijling JL, Olff M, van Zuiden M, Koch SBJ, Nawjin L, Wang L, Zhu Y, Li G, Stein DJ, Ipser J, Seedat S, du Plessis S, van den Heuvel LL, Suarez-Jimenez B, Zhu X, Kim Y, He X, Zilcha-Mano S, Lazarov A, Neria Y, Stevens JS, Ressler KJ, Jovanovic T, van Rooij SJH, Fani N, Hudson AR, Mueller SC, Sierk A, Manthey A, Walter H, Daniels JK, Schmahl C, Herzog JI, Říha P, Rektor I, Lebois LAM, Kaufman ML, Olson EA, Baker JT, Rosso IM, King AP, Liberzon I, Angstadt M, Davenport ND, Sponheim SR, Disner SG, Straube T, Hofmann D, Qi R, Lu GM, Baugh LA, Forster GL, Simons RM, Simons JS, Magnotta VA, Fercho KA, Maron-Katz A, Etkin A, Cotton AS, O'Leary EN, Xie H, Wang X, Quidé Y, El-Hage W, Lissek S, Berg H, Bruce S, Cisler J, Ross M, Herringa RJ, Grupe DW, Nitschke JB, Davidson RJ, Larson CL, deRoon-Cassini TA, Tomas CW, Fitzgerald JM, Blackford JU, Olatunji BO, Kremen WS, Lyons MJ, Franz CE, Gordon EM, May G, Nelson SM, Abdallah CG, Levy I, Harpaz-Rotem I, Krystal JH, Dennis EL, Tate DF, Cifu DX, Walker WC, Wilde EA, Harding IH, Kerestes R, Thompson PM, Morey R

Authors

Carissa W. Tomas PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Terri A. deRoon Cassini PhD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Cerebellum
Female
Gray Matter
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Stress Disorders, Post-Traumatic
White Matter