Abstract
AIMS: This study tends to identify serum biomarkers for early diagnosis of treatment-resistant schizophrenia (TRS) and prediction of clozapine treatment response, given the heterogeneity of schizophrenia and limitations of antipsychotic treatment. PATIENTS & METHODS: Participants of this prospective cohort study (recruited at Shanghai Mental Health Center; 2020-2023) included 42 TRS patients (TRRIP criteria), 42 first-line antipsychotic responders (age/sex-matched 1:1 to TRS), and 70 age/sex-matched healthy controls. TRS patients were stratified post-clozapine into responders (TRS-R, n = 26) and ultra-treatment-resistant (UTRS, n = 16) subgroups. Symptom severity was assessed using PANSS. Serum neuregulin-1 (NRG-1) levels were quantified via ELISA. RESULTS: Healthy controls showed significantly higher NRG-1 levels than schizophrenia patients (F = 39.76, p < 0.001). TRS patients had lower NRG-1 than treatment responders (p < 0.001). Clozapine responders (TRS-R) exhibited increased NRG-1 post-treatment (t = -3.32, p < 0.001), unlike UTRS patients (t = -0.332, p = 0.745). NRG-1 negatively correlated with symptom severity in both TRS (r = -0.647, p < 0.001) and responders (r = -0.596, p < 0.001). NRG-1 demonstrated diagnostic utility for TRS (AUC = 0.827, 95% CI:0.741-0.914; specificity = 0.786, sensitivity = 0.786). CONCLUSION: Serum NRG-1 shows significant promise as a potential biomarker for diagnosing TRS and monitoring clozapine treatment response, suggesting involvement in TRS pathophysiology.