Subgroup-specific brain connectivity alterations in early stages of psychosis

Functional brain scans have shown that connectivity alterations are strongly associated with the first episode of psychosis, yet it is not well understood whether these alterations vary with the clinical status of patients at the time of scanning. This cross-sectional study aimed to identify brain connectivity properties that differentiate remitting and non-remitting early psychosis (EP) patients from healthy controls and to explore the mechanisms underlying these differences. To this end, we analyzed resting-state fMRI and DSI data from 88 EP patients categorized by their remission ability after the first episode of psychosis. We focused on differences between stage III remitting–relapsing (EP3R) and stage III non-remitting (EP3NR) patients. Opposing functional connectivity (FC) alterations were observed: EP3NR patients exhibited lower FC compared with controls, while EP3R patients showed higher FC, possibly reflecting compensatory mechanisms. Whole-brain network modeling revealed lower local stability affecting the ability to regulate the flow of stimuli across the network in stage III patients, particularly in EP3R, which may indicate an adaptation to impaired network conductivity. These findings highlight subgroup-specific brain alterations and underscore the importance of considering this source of heterogeneity in psychosis research. This magnetic resonance imaging study identified distinct brain connectivity profiles for different clinical remission trajectories after a first episode of psychosis.