Persistent Negative Symptoms: Characterization of an Unmet Need in a Learning Health System for First-Episode Psychosis

BACKGROUND AND HYPOTHESIS: Persistent negative symptoms (PNS) often emerge early in the course of schizophrenia spectrum disorders, significantly impair long-term functional outcomes, and remain difficult to treat, with no consistently effective interventions available. The manifestation of PNS in individuals with first-episode psychosis (FEP) engaged in coordinated specialty care (CSC) in the United States remains largely unknown. This study characterizes negative symptoms in routine clinical care using data from the Early Psychosis Intervention Network's Connection Learning Healthcare System, with a focus on a subcohort of individuals with PNS. STUDY DESIGN: Practice-based data were collected every 6 months over a 2-year period from 1289 participants across 23 CSC programs using a Core Assessment Battery (CAB) comprised of clinician-rated and self-report measures. Negative symptoms were quantified across CAB items, allowing for categorization of participants into PNS (n = 79) and non-PNS groups (n = 455). Group comparisons examined outcomes across CAB items, and exploratory mediation analyses focused on the role of engagement in outcomes relative to PNS. STUDY RESULTS: Individuals with PNS had higher rates of schizophrenia and lower social and role functioning compared to those in the non-PNS group. Exploratory analyses indicated that service engagement at 6 months mediated the negative relationship between PNS and 12-month social and role functioning. CONCLUSIONS: These findings highlight the challenge of PNS in individuals with FEP receiving CSC, the importance of early service engagement, and an opportunity to develop targeted interventions and refine treatment approaches to improve outcomes in this unique subgroup.