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A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study

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Title: A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study
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
Source: European Psychiatry, Vol 68 (2025)
Publisher Information: Cambridge University Press, 2025.
Publication Year: 2025
Collection: LCC:Psychiatry
Subject Terms: brain structure, gray matter volume, neuroimaging, PTSD, trauma, voxel-based morphometry, Psychiatry, RC435-571
Description: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 0924-9338
1778-3585
Relation: https://www.cambridge.org/core/product/identifier/S092493382510062X/type/journal_article; https://doaj.org/toc/0924-9338; https://doaj.org/toc/1778-3585
DOI: 10.1192/j.eurpsy.2025.10062
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  Data: European Psychiatry, Vol 68 (2025)
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  Data: Cambridge University Press, 2025.
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  Data: <searchLink fieldCode="DE" term="%22brain+structure%22">brain structure</searchLink><br /><searchLink fieldCode="DE" term="%22gray+matter+volume%22">gray matter volume</searchLink><br /><searchLink fieldCode="DE" term="%22neuroimaging%22">neuroimaging</searchLink><br /><searchLink fieldCode="DE" term="%22PTSD%22">PTSD</searchLink><br /><searchLink fieldCode="DE" term="%22trauma%22">trauma</searchLink><br /><searchLink fieldCode="DE" term="%22voxel-based+morphometry%22">voxel-based morphometry</searchLink><br /><searchLink fieldCode="DE" term="%22Psychiatry%22">Psychiatry</searchLink><br /><searchLink fieldCode="DE" term="%22RC435-571%22">RC435-571</searchLink>
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  Data: 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.
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            – D: 01
              M: 01
              Type: published
              Y: 2025
          Identifiers:
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              Value: 68
          Titles:
            – TitleFull: European Psychiatry
              Type: main
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