Authors

Ashley A Huggins
C Lexi Baird
Melvin Briggs
Sarah Laskowitz
Ahmed Hussain
Samar Fouda
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
Jonathan 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 J H van Rooij
Negar Fani
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 L 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

Language

English

Publication Date

3-1-2024

Journal

Molecular Psychiatry

DOI

10.1038/s41380-023-02352-0

PMID

38195980

PMCID

PMC11153161

PubMedCentral® Posted Date

1-10-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Stress Disorders, Post-Traumatic, Cerebellum, Female, Male, Adult, Magnetic Resonance Imaging, Middle Aged, White Matter, Gray Matter, Organ Size, Deep Learning, Neuroscience, Diagnostic markers, Psychiatric disorders

Published Open-Access

yes

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