Moderate to severe negative symptoms predict low risk of symptoms worsening in schizophrenia patients in CATIE

Understanding factors that predict the course of schizophrenia remains essential for improving long-term clinical management. Rate and severity of symptom exacerbations vary widely across individuals, and although prior studies have examined potential predictors, findings have been inconsistent and often limited by small samples, infrequent assessments, and non-standardized measures. Using data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), which includes a large cohort with monthly standardized evaluations, this study investigated whether baseline negative symptom severity predicts risk of symptom exacerbation over time. Participants were 1139 adults aged 18-65 years meeting DSM-IV criteria for schizophrenia. Symptoms worsening or exacerbation was defined as a [≥]12-point increase from baseline on the PANSS total score. Cox regression survival models examined the association between baseline PANSS negative symptom tertiles and time to exacerbation, adjusting for age, sex, PANSS positive and general psychopathology subscales, and CGI-Severity. Overall, 25.5% of participants experienced exacerbation over a 18-month period of follow-up. Survival curves demonstrated significant separation across negative symptom tertiles (p=0.047), with higher baseline negative symptoms associated with longer time to exacerbation. Compared with the lowest tertile, medium and high negative symptom groups showed reduced exacerbation risk (HR=0.73 and HR=0.69, respectively; both p=0.03). Findings indicate that greater baseline negative symptom severity is associated with a lower likelihood of short-term symptom worsening, suggesting a relatively stable illness course among individuals with more severe negative symptoms. These results have implications for prognosis and treatment planning, while underscoring the persistent functional burden imposed by negative symptoms despite lower exacerbation risk.