Gender-related Characteristics of Oxidative Stress Severity and Cognitive Impairment in Patients With Schizophrenia

Abstract

The gender specificity of the clinical and psychopathological features of schizophrenia is an important factor in this disease. Gender features of neurocognitive deficit in schizophrenia and associated functional and structural disorders of the brain activity are of particular interest to researchers. There are several potential pathogenetic factors of this disease associated with gender, one of which is considered to be oxidative stress. Stress-induced cell death in the prefrontal and anterior frontal regions and reduced brain volume in these regions lead to cognitive and executive decline in patients with schizophrenia. Despite the great interest in the gender factor in schizophrenia pathogenesis, there are currently very few studies on gender differences in the severity of redox imbalance in patients with schizophrenia and their association with neurocognitive deficit. The aim of the study was to reveal the gender specificity of oxidative stress severity in patients with schizophrenia and assess its association with the severity of neurocognitive deficit. The study included 125 patients with schizophrenia and 75 sex- and age-matched healthy volunteers. Sociodemographic and clinical data were studied. Cognitive functions were evaluated using BACS. Blood samples were taken for biochemical studies of the levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) in erythrocyte hemolysate, malonic dialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazones (ADNPH), ketone-2,4-dinitrophenylhydrazones (KDNPH) in plasma. Levels of oxidative stress markers were assessed by spectrophotometric method. In a sample of patients with schizophrenia, a statistically significantly higher activity of CAT was revealed among women compared to men (T=2.25; p=0.025), however, it was lower than in healthy volunteers. But, at the same time, a higher concentration of protein peroxidation products was found in the peripheral blood of women than in men (ADNPH MCO: T=2.52; p=0.013; KDNPH MCO: Z=-2.26; p=0.017). In the group of healthy volunteers, in contrast to patients with schizophrenia, gender differences in markers of oxidative stress were not found. In women with schizophrenia, single correlations were found between the level of the lipid peroxidation product MDA and the test scores for verbal memory (R=-0.36; p=0.006) and working memory (R=-0.36; p=0.006), antioxidant enzyme activity SOD and motor skills (R=-0.26; p=0.047). In men, on the contrary, multiple correlations of both antioxidants and, mainly, products of lipid and protein peroxidation with cognitive functions assessed using BACS were found. Despite the fact that oxidative stress is more pronounced in women than in men with schizophrenia, associations of redox imbalance with neurocognitive deficit in women is much less pronounced than in men.

Keywords: Catalase; Glutathione; Malondialdehyde; Oxidative modification of proteins; Oxidative stress; Schizophrenia; Superoxide dismutase.