BACKGROUND: The pathophysiological mechanisms of schizophrenia are complex and not fully elucidated. This study aimed to investigate changes to total glutathione (T-GSH), glutathione disulfide (GSSG), reduced glutathione (GSH), and the GSH/GSSG ratio before and after electroconvulsive therapy (ECT) for patients with acute relapse of schizophrenia and associations with clinical symptoms. METHODS: The study cohort included 110 patients with acute relapse of schizophrenia and 55 healthy controls. All patients received 8-10 sessions of ECT. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: As compared to the healthy controls, schizophrenia patients had decreased baseline GSSG levels (t = -2.115, p = 0.036) and elevated GSH/GSSG ratios (t = 2.141, p = 0.034). Baseline GSSG levels were negatively correlated with both PANSS total scores (beta = -0.369, t = -4.108, p <
0.001) and positive symptom scores (beta = -0.332, t = -3.730, p <
0.001), while changes to GSSG levels were positively correlated with improvements in PANSS total scores (r = 0.392, p <
0.001) and positive symptom scores (r = 0.293, p = 0.005) after ECT treatment. In treatment responders, GSSG levels were significantly increased (t = -2.817, p = 0.006) and GSH/GSSG ratios were decreased (t = 4.474, p <
0.001), as compared to before ECT, with baseline T-GSH (B = 0.734, OR = 2.083, 95%CI:1.287-3.372, p = 0.003), GSSG (B = -2.720, OR = 0.066, 95%CI:0.011-0.390, p = 0.003), and GSH/GSSG ratio (B = -1.013, OR = 0.363, 95%CI:0.142-0.930, p = 0.035) predictive of clinical improvement. CONCLUSION: Patients with schizophrenia exhibit significant redox imbalance, and GSSG levels may serve as a potential biomarker to evaluate and predict ECT outcomes.