Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

Abstract

Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders

“…The expression of antioxidative genes, i.e., SOD2, PKD1, and NAPG (classic neuroleptics), or BDH1, ACAMD, and NAGS (atypical neuroleptics), as well as the level of proinflammatory cytokines, is also reduced [ 111 ]. Campo et al showed that the use of olanzapine causes a reduction in Acetyl-CoA levels in the mitochondrial cytosol and a weakening of insulin signaling by reducing the phosphorylation of Akt and reducing the expression of Opa-1 protein via the Akt-mTOR-NFκB-Opa-1 signaling pathway [ 109 , 112 ] as we wrote in our previous work [ 50 ].…”

“…Chronic oxidative, nitrosative, or sulfuric stress resulting from oxidant–antioxidant imbalance may be one of the causes of mitochondrial dysfunction and may consistently oxidize lipids, proteins, and DNA impairing their basic biological functions [ 50 ]. MDA formed in the reaction is one of the important markers of oxidative stress and the final product of lipid peroxidation.…”

“…There are many hypotheses trying to explain the causes and mechanisms of this disease. Oxidant–antioxidant imbalance related to the function of the mitochondria discussed above [ 50 ], mitochondrial aberrations [ 43 ], loss of plasticity and reduction of neuronal mass [ 51 ], and insulin resistance [ 51 ].…”

Monitoring the Redox Status in Multiple Sclerosis

“…Together with other RNS, this contributes the damage of cell membranes, proteins, and lipid membrane leading to the degradation of mitochondria, lysosomes, and DNA. The chain of events culminates in the inhibition of immune response and production of carcinogenic nitrosamines [ 125 ]. Nitric oxide (NO) is also involved in metal homeostasis including Fe, Cu, and Zn [ 126 ].…”

Oxidative Stress and Mitochondrial Dysfunction in Human Diseases: Pathophysiology, Predictive Biomarkers, Therapeutic

“…The paper by Bryll et al [ 6 ] extensively reviewed the currently reported role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.…”