Authors

Cheryl R Z See
Shuqing Si
C Lexi Baird
Courtney C Haswell
Ahmed Hussain
Miranda Olff
Dick J Veltman
Jessie L Frijling
Mirjam van Zuiden
Saskia B J Koch
Laura Nawijn
Li Wang
Ye Zhu
Gen Li
Yuval Neria
Xi Zhu
Benjamin Suarez-Jimenez
Sigal Zilcha-Mano
Amit Lazarov
Jennifer S Stevens
Kerry Ressler
Negar Fani
Tanja Jovanovic
Sanne J H van Rooij
Milissa L Kaufman
Lauren A M Lebois
Isabelle M Rosso
Elizabeth A Olson
Justin T Baker
Scott R Sponheim
Seth G Disner
Nicholas D Davenport
Amit Etkin
Adi Maron-Katz
Murray B Stein
Martha E Shenton
Dan J Stein
Jonathan Ipser
Sheri-Michelle Koopowitz
Soraya Seedat
Stefan du Plessis
Leigh L van den Heuvel
Shmuel Lissek
Hannah Berg
Thomas Straube
David Hofman
Lee A Baugh
Gina L Forster
Raluca M Simons
Jeffrey S Simons
Vincent A Magnotta
Kelene A Fercho
Xin Wang
Andrew S Cotton
Erin N O'Leary
Hong Xie
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
Evan M Gordon
Geoffrey May
Steven M Nelson
Ruth Lanius
Jean Théberge
Maria Densmore
Richard W J Neufeld
Chadi G Abdallah
Christopher L Averill
Ilan Harpaz-Rotem
Ifat Levy
John H Krystal
Elbert Geuze
Remko van Lutterveld
Emily L Dennis
David F Tate
David X Cifu
William C Walker
Elisabeth A Wilde
Nic J A van der Wee
Robert R J M Vermeiren
Steven J A van der Werff
Katie McLaughlin
Kelly Sambrook
Matthew Peverill
Joaquim Radua
Lauren E Salminen
Neda Jahanshad
Sophia I Thomopoulos
Anthony James
Lucia Valmaggia
Paul M Thompson
Rajendra A Morey
Matthew J Kempton

Language

English

Publication Date

7-22-2025

Journal

European Psychiatry

DOI

10.1192/j.eurpsy.2025.10062

PMID

40692500

PMCID

PMC12344465

PubMedCentral® Posted Date

7-22-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

Results: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected = .001).

Conclusions: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Keywords

Humans, Stress Disorders, Post-Traumatic, Magnetic Resonance Imaging, Gray Matter, Adult, Male, Female, White Matter, Neuroimaging, Middle Aged, Cerebellum, Brain, brain structure, gray matter volume, neuroimaging, PTSD, trauma, voxel-based morphometry

Published Open-Access

yes

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