Prediction of Psychosis in Youth at High Clinical Risk

TLDR

Early detection of individuals who will develop schizophrenia or other psychotic disorders is essential for understanding psychosis onset and testing prevention, yet current risk prediction models achieve only modest accuracy. The study aimed to estimate conversion risk to psychosis and assess prediction algorithms that maximize positive predictive power in a clinical high‑risk cohort. A 2½‑year longitudinal study of 291 treatment‑seeking patients meeting Structured Interview for Prodromal Syndromes criteria, recruited across eight centers in the North American Prodrome Longitudinal Study, measured time to conversion to a fully psychotic illness. Conversion risk was 35% with a decelerating rate; five baseline features—genetic risk with recent functional decline, unusual thought content, suspicion/paranoia, social impairment, and substance abuse—uniquely predicted psychosis, and algorithms combining 2–3 of these variables raised positive predictive power to 68–80% versus prodromal criteria alone, demonstrating feasible prospective ascertainment with accuracy comparable to other preventive medicine fields.

Abstract

<h3>Context</h3> Early detection and prospective evaluation of individuals who will develop schizophrenia or other psychotic disorders are critical to efforts to isolate mechanisms underlying psychosis onset and to the testing of preventive interventions, but existing risk prediction approaches have achieved only modest predictive accuracy. <h3>Objectives</h3> To determine the risk of conversion to psychosis and to evaluate a set of prediction algorithms maximizing positive predictive power in a clinical high-risk sample. <h3>Design, Setting, and Participants</h3> Longitudinal study with a 2½-year follow-up of 291 prospectively identified treatment-seeking patients meeting Structured Interview for Prodromal Syndromes criteria. The patients were recruited and underwent evaluation across 8 clinical research centers as part of the North American Prodrome Longitudinal Study. <h3>Main Outcome Measure</h3> Time to conversion to a fully psychotic form of mental illness. <h3>Results</h3> The risk of conversion to psychosis was 35%, with a decelerating rate of transition during the 2½-year follow-up. Five features assessed at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse. Prediction algorithms combining 2 or 3 of these variables resulted in dramatic increases in positive predictive power (ie, 68%-80%) compared with the prodromal criteria alone. <h3>Conclusions</h3> These findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. They provide a benchmark for the rate and shape of the psychosis risk function against which standardized preventive intervention programs can be compared.