Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

IF 3.6 Q1 PSYCHIATRY Schizophrenia Research and Treatment Pub Date : 2021-10-13 eCollection Date: 2021-01-01 DOI:10.1155/2021/7721760
T V Zhilyaeva, A S Piatoikina, A P Bavrina, O V Kostina, E S Zhukova, T G Shcherbatyuk, A S Blagonravova, E E Dubinina, G E Mazo
{"title":"Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?","authors":"T V Zhilyaeva,&nbsp;A S Piatoikina,&nbsp;A P Bavrina,&nbsp;O V Kostina,&nbsp;E S Zhukova,&nbsp;T G Shcherbatyuk,&nbsp;A S Blagonravova,&nbsp;E E Dubinina,&nbsp;G E Mazo","doi":"10.1155/2021/7721760","DOIUrl":null,"url":null,"abstract":"<p><p>A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia-disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (<i>p</i> = 0.0041), and this may be due to the lower folate level in patients (<i>p</i> = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (<i>ρ</i> = -0.38, <i>p</i> = 0.0063) and with the level of B12 (<i>ρ</i> = -0.36, <i>p</i> = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (<i>p</i> = 0.00046) and lower catalase (CAT) activity (<i>p</i> = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 <i>μ</i>mol/l, <i>n</i> = 42) compared with other patients (<i>n</i> = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, <i>p</i> = 0.019), lack of spontaneity and flow in conversation (N6, <i>p</i> = 0.022), stereotyped thinking (N7, <i>p</i> = 0.013), and motor retardation (G7, <i>p</i> = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.</p>","PeriodicalId":45388,"journal":{"name":"Schizophrenia Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2021-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545596/pdf/","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Schizophrenia Research and Treatment","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2021/7721760","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 6

Abstract

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia-disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (p = 0.0041), and this may be due to the lower folate level in patients (p = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (ρ = -0.38, p = 0.0063) and with the level of B12 (ρ = -0.36, p = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (p = 0.00046) and lower catalase (CAT) activity (p = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 μmol/l, n = 42) compared with other patients (n = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019), lack of spontaneity and flow in conversation (N6, p = 0.022), stereotyped thinking (N7, p = 0.013), and motor retardation (G7, p = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
同型半胱氨酸与精神分裂症:具有促氧化活性的独立致病因子还是其他生化紊乱的整体标志?
广泛的研究表明,高同型半胱氨酸血症与精神分裂症的风险相关,但目前关于同型半胱氨酸(Hcy)直接参与精神分裂症发病机制的假设是假设的。在体内,Hcy可能只是叶酸代谢紊乱(涉及甲基化过程)的一个标志,本身并不是一个致病因素。只有一项研究发现高同型半胱氨酸血症与精神分裂症患者氧化应激(对蛋白质和脂质的氧化损伤)之间存在关联,并提示氧化应激可能是由精神分裂症患者Hcy升高引起的。但作者没有研究还原型谷胱甘肽(GSH)的水平,以及高同型半胱氨酸血症(叶酸代谢紊乱)的可能原因。本研究旨在分析Hcy水平与以下因素的关系:(1)精神分裂症GSH中的氧化还原标志物、蛋白质和脂质氧化损伤标志物以及血清中抗氧化酶活性;(2)叶酸和钴胺素水平(В12);(3)使用阳性和阴性症状量表(PANSS)测量精神分裂症的临床特征。研究人员对50名精神分裂症患者和36名按性别和年龄匹配的健康志愿者进行了研究。患者的Hcy高于健康受试者(p = 0.0041),这可能是由于患者的叶酸水平较低(p = 0.0072)。在患者中,Hcy水平与叶酸水平(ρ = -0.38, p = 0.0063)和B12水平(ρ = -0.36, p = 0.0082)呈负相关。同时,患者血清蛋白氧化修饰水平升高(p = 0.00046),过氧化氢酶(CAT)活性降低(p = 0.014)。然而,Hcy与所研究的患者氧化应激标志物无关。Hcy水平升高组(>10 μmol/l, n = 42)与其他组(n = 8)相比,一些阴性症状(PANSS)更明显:抽象思维困难(N5, p = 0.019)、谈话缺乏自发性和流畅性(N6, p = 0.022)、刻板思维(N7, p = 0.013)、运动迟缓(G7, p = 0.050)。因此,在精神分裂症患者中,由叶酸和B12缺乏引起的高同型半胱氨酸血症得到证实,可被认为是维生素代谢紊乱的标志。氧化还原失衡可能与高同型半胱氨酸血症没有直接关系,假设是由其他病理过程引起的,或者是由Hcy的间接作用引起的,例如,对酶抗氧化防御系统(CAT活性)的影响,这需要进一步探索。进一步研究Hcy在精神分裂症发病机制中的作用是有意义的,因为高同型半胱氨酸血症患者的比例很高,并且注意到其水平与精神分裂症阴性症状的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
4.60
自引率
0.00%
发文量
2
审稿时长
14 weeks
期刊介绍: Schizophrenia Research and Treatment is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to all aspects of schizophrenia.
期刊最新文献
Adherence to Typical Antipsychotics among Patients with Schizophrenia in Uganda: A Cross-Sectional Study. Investigating Body Mass Index and Body Composition in Patients with Schizophrenia: A Case-Control Study Cigarette Smoking and Schizophrenia: Etiology, Clinical, Pharmacological, and Treatment Implications. Comparison of Efficacy and Safety between Long-Acting Injectable Antipsychotic Monotherapy and Combination of Long-Acting Injectable and Oral Antipsychotics in Patients with Schizophrenia. Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1