This single-center, prospective cohort study will enroll 200 drug-naive schizophrenia patients and 100 demographically matched healthy volunteers to identify biological signatures of cognitive impairment and to develop predictive models for subsequent change. At baseline we will administer the MATRICS Consensus Cognitive Battery (MCCB), clinical rating scales, multimodal magnetic resonance imaging (MRI), and collect fasting blood and first-morning urine for multi-omics assays. Participants are re-evaluated at 4, 8 and 12 weeks during naturalistic antipsychotic treatment, repeating cognitive testing, clinical scales, and blood/urine sampling. Primary analyses will link baseline omics to the MCCB overall composite score; secondary analyses will model the longitudinal trajectories of both cognition and biomarkers to derive parsimonious predictors of cognitive gain versus persistent impairment. The resulting biomarker panels are expected to inform future stratified clinical trials and mechanism-based cognitive remediation strategies.
