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精神分裂症患者氧化应激严重程度与认知障碍的性别相关特征。

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

作者信息

Piatoikina Anna Sergeevna, Zhilyaeva Tatiana Vladimirovna, Kostina Olga Vladimirovna, Zhukova Evgeniya Sergeevna, Shcherbatyuk Tatiana Grigorievna, Mazo Galina Elevna

机构信息

State Budgetary Institution of Public Health of Nizhny Novgorod Region "Nizhny Novgorod Clinical Psychiatric Hospital No. 1", Nizhny Novgorod, Russia.

Federal State Budgetary Institution "V.M. Bekhterev National Research Medical Center for Psychiatry and Neurology", Saint-Petersburg, Russia.

出版信息

J Mol Neurosci. 2023 Aug;73(7-8):628-634. doi: 10.1007/s12031-023-02140-z. Epub 2023 Aug 5.

DOI:10.1007/s12031-023-02140-z
PMID:37542578
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.

摘要

精神分裂症临床和精神病理学特征的性别特异性是该疾病的一个重要因素。精神分裂症神经认知缺陷的性别特征以及相关的大脑活动功能和结构障碍尤其引起研究人员的兴趣。该疾病有几个与性别相关的潜在致病因素,其中之一被认为是氧化应激。应激诱导的前额叶和额叶前部区域细胞死亡以及这些区域脑容量减少导致精神分裂症患者出现认知和执行功能下降。尽管对精神分裂症发病机制中的性别因素有很大兴趣,但目前关于精神分裂症患者氧化还原失衡严重程度的性别差异及其与神经认知缺陷的关联的研究非常少。本研究的目的是揭示精神分裂症患者氧化应激严重程度的性别特异性,并评估其与神经认知缺陷严重程度的关联。该研究纳入了125名精神分裂症患者和75名年龄和性别匹配的健康志愿者。研究了社会人口统计学和临床数据。使用BACS评估认知功能。采集血样用于红细胞溶血产物中还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平,血浆中丙二醛(MDA)、醛 - 2,4 - 二硝基苯腙(ADNPH)、酮 - 2,4 - 二硝基苯腙(KDNPH)的生化研究。通过分光光度法评估氧化应激标志物水平。在精神分裂症患者样本中,女性的CAT活性在统计学上显著高于男性(T = 2.25;p = 0.025),然而,低于健康志愿者。但与此同时,女性外周血中蛋白质过氧化产物的浓度高于男性(ADNPH MCO:T = 2.52;p = 0.013;KDNPH MCO:Z = -2.26;p = 0.017)。与精神分裂症患者相比,在健康志愿者组中未发现氧化应激标志物的性别差异。在患有精神分裂症的女性中,发现脂质过氧化产物MDA水平与言语记忆测试分数(R = -0.36;p = 0.006)和工作记忆测试分数(R = -0.36;p = 0.006)之间存在单相关性,抗氧化酶活性SOD与运动技能之间存在单相关性(R = -0.26;p = 0.047)。相反,在男性中,发现抗氧化剂以及主要是脂质和蛋白质过氧化产物与使用BACS评估的认知功能之间存在多重相关性。尽管氧化应激在患有精神分裂症的女性中比男性更明显,但女性氧化还原失衡与神经认知缺陷的关联比男性要弱得多。

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