Abnormal eye movement, brain regional homogeneity in schizophrenia and clinical high-risk individuals and their associated gene expression profiles

Clinical high-risk (CHR) is a prodromal period before psychosis characterized by attenuated, transient, or intermittent psychotic symptoms and declining functioning. They exhibit eye movement abnormalities and brain functional damage compared with schizophrenia, potentially increasing vulnerability to psychosis. This study investigates eye movement dysfunction and brain activity alterations in CHR and first-episode schizophrenia (FSZ) individuals to identify early biomarkers for psychosis progression. Twenty-seven drug-naïve FSZ, 25 CHR, and 28 healthy controls (HCs) were recruited for eye-tracking tasks and resting-state functional magnetic resonance imaging to evaluate eye movement and regional homogeneity (ReHo) differences. Machine-learning algorithms were used to differentiate FSZ from CHR. In combination with the Allen Human Brain Atlas (AHBA), transcriptome-neuroimaging analysis was applied to identify ReHo-related gene expression profiles. FSZ exhibited a wide range of eye movement abnormalities across multiple tasks, while certain abnormalities were already present in CHR. Abnormal ReHo alterations were found in orbitofrontal gyrus, temporal gyrus, and cingulum among three groups, associated with specific eye movement parameters. These differences in eye movement and ReHo allowed for high-accuracy discrimination between them. Genetic analysis identified significant genes in FSZ and CHR, enriched in various biological functions and pathways (all corrected p < 0.05). FSZ and CHR exhibited different eye movement and ReHo patterns, indicating potential as early biomarkers. Our findings reveal correlations between these ReHo patterns and gene expression profiles using AHBA database, shedding light on possible genetic mechanisms underlying brain function in FSZ and CHR.