Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals

Background: Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR individuals with different clinical outcomes, and (3) whether non-remission (persistent APS or transition) can be predicted using baseline and/or longitudinal data. Study design: Participants were drawn from 2 randomized clinical trials: Neurapro (n = 220; discovery sample) and STEP (n = 180; external validation sample). First, 12-24 month symptoms and functioning were compared between UHR individuals with persistent APS, sustained remission, or transition to psychosis. Next, short-term changes in symptoms and functioning were compared between groups to determine timepoints at which trajectories began to diverge. Finally, we used support vector machines to predict non-remission (persistent APS or transition) vs sustained remission using data from baseline, 6-month follow-up, and combined baseline and 6-month follow-up. Results: Individuals with persistent APS had substantially poorer outcomes compared to those who remitted, and more closely resembled individuals who later transitioned to psychosis. Despite few baseline differences between groups, clinical and functional trajectories of the persistent APS and transition groups rapidly diverged from those who remitted. Prediction of non-remission was poor using baseline data but improved substantially when using 6-month follow-up or combined baseline-6-month data. Conclusions: Ultra-high-risk individuals with persistent APS display similar clinical and functional trajectories to transitioned cases, suggesting that more intensive and sustained intervention is required for this subgroup. However, prospective identification of individuals with poor clinical outcomes (ie, persistence or deterioration of attenuated psychotic symptoms) may require longitudinal monitoring of symptom and functioning trajectories for several months.