Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functionalimpairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive modelseither included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes(SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. Wealso conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N andgyrification model. Additionally, we assessed the models’ability to predict functional outcomes in CHR and theirtransdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negativesymptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy.Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regardingtheir risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was alsoable to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification modelachieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only thebaseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodalprognostic model to identify those CHR with a clinically relevant negative symptom severity and functionalimpairments, potentially requiring further therapeutic consideration.