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Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

Si, S., Bi, A., Yu, Z. , See, C., Kelly, S., Ambrogi, S., Arango, C., Baeza, I., Banaj, N., Berk, M., Castro-Fornieles, J., Crespo-Facorro, B., Crouse, J. J., Díaz-Caneja, C. M., Fett, A-K. ORCID: 0000-0003-0282-273X, Fortea, A., Frangou, S., Goldstein, B. I., Hickie, I. B., Janssen, J., Kennedy, K. G., Krabbendam, L., Kyriakopoulos, M., MacIntosh, B. J., Morgado, P., Nerland, S., Pascual-Diaz, S., Picó-Pérez, M., Piras, F., Rund, B. R., de la Serna, E., Spalletta, G., Sugranyes, G., Suo, C., Tordesillas-Gutiérrez, D., Vecchio, D., Radua, J., McGuire, P., Thomopoulos, S. I., Jahanshad, N., Thompson, P. M., Barth, C., Agartz, I., James, A. & Kempton, M. J. (2024). Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study. Molecular Psychiatry, doi: 10.1038/s41380-023-02343-1


INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.

RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.

CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Publication Type: Article
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Publisher Keywords: Neuroscience, Psychiatric disorders
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments: School of Health & Psychological Sciences > Psychology
SWORD Depositor:
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