563. Plasma interleukin-6 levels in antipsychotic-responsive and treatment-resistant schizophrenia in association with clozapine treatment
Abstract
Abstract Background Neuroinflammation has been proposed as a key pathophysiological mechanism underlying treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) has been reported as a trait-related inflammatory marker in schizophrenia; however, data focusing specifically on TRS and the impact of clozapine treatment remain limited. Aims & Objectives The aim of the present study was to investigate differences in plasma IL-6 levels between TRS and antipsychotic-responsive schizophrenia (AR). Specifically, we aimed to clarify the associations between plasma IL-6 levels and clinical symptoms, cognitive function, and clozapine treatment in TRS. Method We conducted a multicenter cross-sectional study including patients with TRS and AR. Plasma IL-6 levels were measured and compared between the two groups. Cognitive function and clinical variables were assessed, and factors associated with plasma IL-6 levels were examined within the TRS group. Results A total of 62 patients (37 patients with TRS and 25 with AR) were included. Plasma IL-6 levels were significantly higher in TRS than in AR (p < 0.001). Within the TRS group, plasma IL-6 levels were negatively associated with the duration of clozapine treatment (r = −0.348, p < 0.05; Figure1). This association remained significant after adjustment for age in multiple regression analysis (β = −0.435, p = 0.007). No significant associations were observed between plasma IL-6 levels and symptom severity or cognitive function within the TRS group. Discussion & Conclusions These findings support the concept that TRS represents a biologically distinct subtype of schizophrenia characterized by inflammatory dysregulation. Moreover, longer-term clozapine treatment may exert anti-inflammatory effects in TRS, highlighting a potential immunomodulatory role of clozapine beyond symptom control. Further longitudinal studies are warranted to clarify the causal relationship between clozapine treatment and inflammatory processes.