Oxidative Stress in Schizophrenia: Relation to Neurochemical Pathogenetic Hypotheses

Abstract

   Background: heterogeneity of schizophrenia is reflected in the variety of clinical manifestations and biological disorders, on the basis of which several neurochemical hypotheses are formulated for schizophrenia pathogenesis. Review of the current hypotheses of schizophrenia pathogenesis shows that oxidative stress is not the main cause of the disease development, but affects its course and contributes to the deterioration of the patient’s condition.   Objective: analysis of the relationships between redox imbalance and oxidative stress and the development of pathological processes in schizophrenia within the framework of neurochemical hypotheses of the disease pathogenesis.   Material and methods: a search was made for sources in the Medline/PubMed databases, Scopus and RSCI using keyword combinations “oxidative stress”, “oxidation-reduction imbalance”, “schizophrenia”, “hypotheses of schizophrenia pathogenesis”, “antioxidants”, “neurotransmitters”, “glutathione”, “neuroinflammation”.   Conclusion: data from numerous studies of the brain of patients with schizophrenia, their blood plasma, serum, and blood cells as well as the study of animal models of schizophrenia indicate the presence of redox imbalance and oxidative stress in this disease. Taken together, these data indicate that genetic and environmental factors that affect the manifestation of various pathological mechanisms in schizophrenia (disturbances in neurotransmitter systems, hypofunction of N-methyl-D-aspartate receptors, neuroinflammation, impaired signaling protein phosphorylation pathways) lead to the oxidative stress, enhancing the initial pathological changes, as a result of which synchronization processes and intercellular communications in the brain become disrupted. Medicines with antioxidant and anti-inflammatory properties, compounds for correcting mitochondrial dysfunction, and NMDAR-mediated signaling modulators can be used as drugs to reduce the harmful effects of oxidative stress. The efficacy of these medicines may vary in different patients, so the development of biomarker systems aimed at identifying individuals who are more likely to respond to a particular drug is of great importance.