Gray Matter Volume Abnormalities and the Association with the Trajectory of Symptoms and Functioning in Individuals at Clinical High Risk of Psychosis

Journal article

Background: Brain volume alterations in those at clinical high risk (CHR) of psychosis have been reported in many studies. However, the association between these alterations and the longitudinal trajectory of changes in symptoms and functioning remains unexplored. Study Design: T1-weighted magnetic resonance imaging (MRI) scans were acquired from 226 CHR and 65 healthy controls (HC) recruited from the EU-GEI high-risk study. Five a priori regions of interest were examined and segmented using FreeSurfer: total gray matter (GM) volume, anterior cingulate cortex (ACC), hippocampus, fusiform gyri, and insula. Brain volumes in the CHR and HC groups were compared at baseline. In the CHR group, linear mixed models were used to investigate the association between baseline brain volume and longitudinal changes in positive symptoms, negative symptoms, and functioning over a 2-year follow-up period. We also compared CHR participants who later transitioned to psychosis (CHR-T, n = 48) and those who did not (CHR-NT, n = 178) in terms of their trajectory of symptoms and functioning. Study Results: Compared with HC, CHR participants had lower total GM and fusiform volume at baseline. Lower total GM and hippocampus volume at baseline were associated with higher levels of positive symptoms at baseline and follow-up in CHR individuals, and lower baseline hippocampus volume also predicted future transition. CHR-T and CHR-NT individuals demonstrated distinct symptoms and functioning trajectories over time. Conclusion: Our findings suggest that CHR individuals show baseline differences in brain structure compared to HC, which may also predict changes in positive symptoms over the subsequent 2 years.

Authors: Si, S; See, C; Hedges, EP; Tognin, S; Modinos, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Schizophrenia Bulletin: The Journal of Psychoses and Related Disorders
• Article number: sbaf231
• Publication date: 2025-12-23
• Acceptance date: 2025-11-29
• DOI: 10.1093/schbul/sbaf231
• EISSN: 1745-1701
• ISSN: 0586-7614
• Language: English
• Keywords: sMRI; clinical high risk; gray matter volume; psychosis