Neurotrophins and Matrix Metalloproteinases in Treatment-Resistant Schizophrenia: Effects of Electroconvulsive Therapy on Serum Biomarkers and Clinical Outcomes: A Preliminary Study

Background: Available data indicate that the development of refractory schizophrenia may result from neuroinflammation, dysregulation of neurotrophins and metalloproteinases (MMPs), oxidative stress (OS), and hormonal imbalance. Electroconvulsive therapy (ECT) is an effective therapeutic option for drug resistance, but its impact on brain-derived neurotrophic factor (BDNF) and MMPs remains underinvestigated. This study evaluates the influence of ECT on serum BDNF, MMPs (MMP-7, MMP-9, MMP-14), and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3) in patients with treatment-resistant schizophrenia (TRS). Another goal of this study is an assessment of the relationships between these biomarkers and the intensity of schizophrenia symptoms. Methods: Serum concentrations of the aforementioned biomarkers were measured prior to and after ECT in eight patients and 13 healthy controls. The severity of schizophrenia symptoms was evaluated with the Positive and Negative Syndrome Scale (PANSS). Results: Bayesian analysis comparing pre-ECT serum concentrations of BDNF, MMPs, and their inhibitors in TRS patients with a control group showed a significant difference only for MMP-9. Furthermore, convincing evidence of a correlation between MMP-9 and MMP-14 was found in TRS patients. Although the ECT therapy did not result in changes in the serum concentrations of the studied biomarkers, substantial improvement in schizophrenia symptoms on the PANSS was observed. Conclusions: No significant biomarker changes (post- versus pre-treatment) were detected in this small exploratory cohort. Whether these biomarkers are involved in neuroinflammation (as possible contributors to the development of TRS) remains an open question, and therefore, further research on biomarkers in cerebrospinal fluid (CSF) may be suggested.