Dynamic, differentiated clinical trajectories and prediction in clinical high risk for psychosis

Clinical subtypes of individuals at clinical high risk for psychosis (CHR), classified by baseline symptoms and cognitive performance, may follow distinct trajectories of symptom progression and functional outcomes. Baseline symptom, cognitive and EEG data were collected from 204 CHR individuals aged 13-38 years, who subsequently completed clinical assessments at 2 months, 1 year, and 2 years. Although baseline positive symptom scores and highest past-year global functioning did not differ significantly, the subtypes demonstrated divergent progression patterns across follow-ups. Baseline cognitive performance exerted sustained influence over subsequent assessments, with visuospatial learning and working memory showing significant long-term effects on positive symptoms or global functioning, highlighting them as core cognitive domains with longitudinal, cross-subtype impact on CHR progression. Brain network features also contributed to long-term outcomes. The involvement of microstate D was sustained over time, with its occurrence linked to functional outcomes in the most impaired subtype and its coverage associated with positive symptom trajectories in the moderately impaired subtype. We further constructed a predictive model incorporating the interaction between microstate D and subtype that effectively identified individuals who converted to psychosis, underscoring its potential as a dynamic biomarker for more precise CHR clinical profiles.