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

Helene Speyer; Jonathan Rabinowitz; Remy Luthringer; Bogdan Ionel Tamba; Michael Davidson

doi:10.1016/j.schres.2026.06.004

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

Schizophr Res. 2026 Jun 6:295:150-155. doi: 10.1016/j.schres.2026.06.004. Online ahead of print.

Authors

Helene Speyer¹, Jonathan Rabinowitz², Remy Luthringer³, Bogdan Ionel Tamba⁴, Michael Davidson³

Affiliations

¹ Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania; Mental Health Services in the Capital Region of Denmark, Denmark.
² Bar-Ilan University, Israel. Electronic address: Jonathan.Rabinowitz@biu.ac.il.
³ Minerva Neurosciences, USA.
⁴ Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania.

PMID: 42250382
DOI: 10.1016/j.schres.2026.06.004

Abstract

Understanding predictors of schizophrenia course is critical for long-term clinical management, yet prior findings have been inconsistent due to 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, years since first prescribed antipsychotic medication, randomized antipsychotic treatment group, PANSS positive and general psychopathology subscales, and CGI-Severity. Overall, 25.5% of participants experienced exacerbation over an 18-month period of follow-up. Survival curves demonstrated significant separation across negative symptom tertiles (p < 0.05), 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 = 0.72 and HR = 0.70, respectively; both p < 0.04). 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.

Keywords: CATIE trial; Negative symptoms; PANSS (Positive and Negative Syndrome Scale); Relapse prediction; Schizophrenia; Symptom exacerbation.