Predictors and Moderators of Long-Term Outcome of Persons at Clinical High Risk for Psychosis: Methods and Preliminary Data

Background and Hypothesis Despite significant advances in our understanding of the clinical high risk (CHR) for psychosis state, the longer-term outcomes (5+ years) and the trajectory of diagnoses, symptoms, and psychosocial function have been seldom investigated. Objective Here we describe the methods for “Predictors and Moderators of Long-Term Outcome of Persons at Clinical High Risk for Psychosis,” an ongoing study that is being conducted across North American Prodrome Longitudinal Studies sites that included n = 2184 past participants (1999-2018). Study Design The aims are to: (1) perform long-term assessments of individuals who previously met CHR criteria, (2) determine the 5+ year psychotic conversion rate and use previously collected longitudinal clinical, functional, neurocognitive, and biomarker data to predict longer term outcomes, and (3) investigate predictors of long-term clinical/functional outcome in CHR participants who did not convert to psychosis. Study Results Preliminary results from the first n = 504 participants demonstrate that 60% of those who previously met CHR criteria are still symptomatic. Eighteen percent of past participants converted to psychosis, half in the original studies and the remainder since last evaluated. Of those who converted to psychosis, the majority met criteria for an affective psychosis, consistent with the high rate of affective disorders (70%) in the non-converted group. An additional 7% of past participants died, substantially higher than the general population. Conclusions These early data highlight the potential of how this dataset, when combined with baseline data, can be used to answer new questions about the life course of high-risk youth and how we might intervene early to improve their long-term outcome.