氧化应激与精神分裂症的研究现况

大量的研究表明氧化应激是精神分裂症的病理生理机制之一。在精神分裂症的早期即可观察到氧化应激指标升高以及抗氧化系统受损,高氧化状态导致机体组织如脂质、蛋白以及核酸损伤,无论是首发还是服药治疗的慢性精神分裂症中都可观察到氧化抗氧化系统失衡,提示氧化应激存在于精神分裂症中。抗精神病药物在改善精神分裂症临床症状的同时也会对氧化应激起到一定影响,抗氧化剂作为抗精神病药物的增效药物对精神分裂症临床症状的改善也有一定的疗效,抗精神病药物联合抗氧化剂或许可以作为精神分裂症的一种新的有效治疗策略。     

精神分裂症代谢综合征与氧化应激相关性的研究进展

精神分裂症是一种严重的精神疾病，常伴有代谢综合征和氧化应激，而代谢综合征和氧 化应激可相互作用。抗氧化剂可用于治疗精神分裂症，对其代谢综合征亦有疗效。现对精神分裂症代 谢综合征与氧化应激相关研究进展进行综述。     

精神分裂症与氧化应激相关机制研究进展

精神分裂症是一种机制复杂的常见精神障碍.氧化应激已经被证实在精神分裂症的病理过程中发挥重要作用.通过检测外周血、脑脊液中氧化应激标志物含量,可以观察到精神分裂症患者普遍存在氧化还原失衡,而抗氧化剂的应用可以减少氧化应激损伤,改善精神分裂症患者的部分症状.氧化应激通过在神经发育的关键时期诱导神经炎症反应、影响少突胶质前体细胞成熟过程、降低N-甲基-D-天冬氨酸受体功能活性、损害小清蛋白中间神经元功能等可能机制,导致一系列精神行为异常的发生.     

氧化应激参与精神分裂症认知功能障碍机制的研究进展

精神分裂症是一种成年人群终身患病率约为1%的慢性精神障碍,主要的核心症状为阳性症状、阴性症状和认知症状。越来越多研究发现氧化应激参与了精神分裂症的病理机制,并和认知功能损害紧密相关。本文通过对近几年国内外学者的研究做一综述,了解氧化应激与精神分裂症认知功能的关系。     

TRPV1在中枢神经系统中的双重作用及其参与精神分裂症的可能机制

瞬时受体电位香草酸亚型 1（TRPV1）在中枢神经系统广泛分布,并在氧化应激、神经炎 症、神经凋亡、突触损伤方面均发挥了双重作用。精神分裂症是一组以阳性症状、阴性症状、精神运动 性障碍及现实检验能力严重受损为特征表现的精神障碍,其发病机制尚未完全阐明。目前研究发现, TRPV1可能在精神分裂症中发挥潜在作用。本文对TRPV1在中枢神经系统中的双重作用进行归纳总结, 以期解释 TRPV1 参与精神分裂症的可能机制。     

首发精神分裂症外周血氧化应激状态改变

目的探讨首发精神分裂症患者外周血氧化应激变化及抗精神病药治疗对其影响。方法纳入47例首发未用药精神分裂症患者和43名正常对照,测定其外周血总超氧化物歧化酶(total superoxide dismutase,T-SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)及总抗氧化能力(total antioxidant capacity of the body,T-AOC)活性。患者中18例完成单一利培酮6周治疗(利培酮组),25例完成单一奥氮平6周治疗(奥氮平组),治疗后再次测定外周血T-SOD、GSH-Px、CAT及T-AOC。结果与对照组相比,患者组治疗前T-SOD、GSH-Px降低(P0.05),CAT升高(P0.05),T-AOC差异无统计学意义(P0.05)。利培酮组T-SOD活性在治疗后升高(P0.05),奥氮平组T-AOC在治疗后升高(P0.05),两组各氧化应激指标的变化值组间差异均无统计学意义(P0.05)。结论首发精神分裂症患者抗氧化酶活性改变,这可能与精神分裂症病理机制有关。非典型抗精神病药利培酮和奥氮平可改善首发精神分裂症患者的氧化应激状态。     

精神分裂症患者认知功能损害与氧化应激关系的初步研究

目的：探讨精神分裂症患者认知功能缺损与氧化应激的关系。方法：对39例精神分裂症患者（患者组），36名健康对照者（对照组）进行神经心理测验和氧化应激指标的检测.结果：（1）在神经心理测验中，患者组与对照组在总测验数、总错误数、持续错误数、语言流畅、领悟、相似和联想学习的差异有非常显著性（P＜0．01），数字广度的差异有显著性（P＜0．05）；（2）患者组后的一氧化氮（NO）浓度与WCST的总错误数呈显著正相关，与相似测验呈显著性负相关，超氧化物歧化酶（SOD）活性与相似性测验、数字广度测验呈显著性负相关（r分别为0．409，－0．404，－0．432，－0．420，P＜0．05）。结论：（1）精神分裂症认知功能缺损的生物学基础可能与氧化应激有关；（2）SOD和NO可能是与认知功能密切相关的氧化应激指标。     

氧化应激与精神分裂症的研究进展

阐述氧化应激与精神分裂症的病因、症状及治疗的关系     

维生素D3辅助治疗对首发精神分裂症患者血清神经营养因子、氧化应激指标及临床疗效的影响

目的:探讨维生素D3(VD3)辅助治疗对首发精神分裂症患者血清神经营养因子、氧化应激指标及临床疗效的影响.方法:将120例首发精神分裂症患者随机分为两组,且均给予利培酮治疗16周;在此基础上,干预组加服VD3(800 IU/d),对照组每日服用安慰剂.根据治疗前后阳性与阴性症状量表(PANSS)评分来判断疗效;治疗前后...     

开放式与封闭式病房精神分裂症患者生存质量的比较

目的探讨开放式与封闭式病房模式对精神分裂症患者生存质量的影响。方法按入组标准选取我院开放式病房精神分裂症患者38例,封闭式45例。采用世界卫生组织生存质量评定量表（WHO QOL-100）、简明精神评定量表（BPRS）评定,并进行对比研究。结果开放式病房中的精神分裂症患者的生理领域、心理领域等WHO QOL-100评分高于对照组。结论开放式病房中的精神分裂症患者生存质量高于封闭式病房中的精神分裂症患者生存质量。     

Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia

1. Schizophrenia is a major mental disorder that has a lifetime risk of 1% and affects at young age (average age at the onset 24 +/- 4.6 years) in many cultures around the world. The etiology is unknown, the pathophysiology is complex, and most of the patients need treatment and care for the rest of their lives. 2. Cellular oxidative stress is inferred from higher tissue levels of reactive oxygen species (ROS, e.g., O2*-, OH*, OH-, NO* and ONOO--) than its antioxidant defense that cause peroxidative cell injury, i.e., peroxidation of membrane phospholipids, particularly esterified essential polyunsaturated fatty acids (EPUFAS), proteins and DNA. 3. Oxidative stress can lead to global cellular with predominantly neuronal peroxidation, since neurons are enriched in highly susceptible EPUFAs and proteins, and damages DNA is not repaired effectively. 4. Such neuronal peroxidation may affect its function (i.e., membrane transport, loss of mitochondrial energy production, gene expression and therefore receptor-mediated phospholipid-dependent signal transduction) that may explain the altered information processing in schizophrenia. 5. It is possible that the oxidative neuronal injury can be prevented by dietary supplementation of antioxidants (e.g., vitamins E, C and A; beta-carotene, Q-enzyme, flavons, etc.) and that membrane phospholipids can be corrected by dietary supplementation of EPUFAs. 6. It may be that the oxidative stress is lower in populations consuming a low caloric diet rich in antioxidants and EPUFAs, and minimizing smoking and drinking. 7. Oxidative stress exists in schizophrenia based on altered antioxidant enzyme defense, increased lipid peroxidation and reduced levels of EPUFAs. The life style of schizophrenic patients is also prooxidative stress, i.e., heavy smoking, drinking, high caloric intake with no physical activity and treatment with pro-oxidant drugs. 8. The patients in developed countries show higher levels of lipid peroxidation and lower levels of membrane phospholipids as compared to patients in the developing countries. 9. Initial observations on the improved outcome of schizophrenia in patients supplemented with EPUFAs and antioxidants suggest the possible beneficial effects of dietary supplementation. 10. Since the oxidative stress exists at or before the onset of psychosis the use of antioxidants from the very onset of psychosis may reduce the oxidative injury and dramatically improve the outcome of illness.     

Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia

Schizophrenia is associated with a broad range of neurodevelopmental, structural and behavioral abnormalities that often progress with or without treatment. Evidence indicates that such neurodevelopmental abnormalities may result from defective genes and/or non-genetic factors such as pre-natal and neonatal infections, birth complications, famines, maternal malnutrition, drug and alcohol abuse, season of birth, sex, birth order and life style. Experimentally, these factors have been found to cause the cellular metabolic stress that often results in oxidative stress, such as increased cellular levels of reactive oxygen species (ROS) over the antioxidant capacity. This can trigger the oxidative cell damage (i.e., DNA breaks, protein inactivation, altered gene expression, loss of membrane lipid-bound essential polyunsaturated fatty acids [EPUFAs] and often apoptosis) contributing to abnormal neural growth and differentiation. The brain is preferentially susceptible to oxidative damage since it is under very high oxygen tension and highly enriched in ROS susceptible proteins, lipids and poor DNA repair. Evidence is increasing for increased oxidative stress and cell damage in schizophrenia. Furthermore, treatments with some anti-psychotics together with the lifestyle and dietary patterns, that are pro-oxidant, can exacerbate the oxidative cell damage and trigger progression of neuropathology. Therefore, adjunctive use of dietary antioxidants and EPUFAs, which are known to regulate the growth factors and neuroplasticity, can effectively improve the clinical outcome. The dietary supplementation of either antioxidants or EPUFAs, particularly omega-3 has already been found to improve some psychopathologies. However, a combination of antioxidants and omega-3 EPUFAs, particularly in the early stages of illness, when brain has high degree of neuroplasticity, potentially may be even more effective for long-term improved clinical outcome of schizophrenia.     

Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia

Summary

Schizophrenia is associated with a broad range of neurodevelopmental, structural and behavioral abnormalities that often progress with or without treatment. Evidence indicates that such neurodevelopmental abnormalities may result from defective genes and/or non-genetic factors such as pre-natal and neonatal infections, birth complications, famines, maternal malnutrition, drug and alcohol abuse, season of birth, sex, birth order and life style. Experimentally, these factors have been found to cause the cellular metabolic stress that often results in oxidative stress, such as increased cellular levels of reactive oxygen species (ROS) over the antioxidant capacity. This can trigger the oxidative cell damage (i.e., DNA breaks, protein inactivation, altered gene expression, loss of membrane lipid-bound essential polyunsaturated fatty acids [EPUFAs] and often apoptosis) contributing to abnormal neural growth and differentiation. The brain is preferentially susceptible to oxidative damage since it is under very high oxygen tension and highly enriched in ROS susceptible proteins, lipids and poor DNA repair. Evidence is increasing for increased oxidative stress and cell damage in schizophrenia. Furthermore, treatments with some anti-psychotics together with the lifestyle and dietary patterns, that are pro-oxidant, can exacerbate the oxidative cell damage and trigger progression of neuropathology. Therefore, adjunctive use of dietary antioxidants and EPUFAs, which are known to regulate the growth factors and neuroplasticity, can effectively improve the clinical outcome. The dietary supplementation of either antioxidants or EPUFAs, particularly omega-3 has already been found to improve some psychopathologies. However, a combination of antioxidants and omega-3 EPUFAs, particularly in the early stages of illness, when brain has high degree of neuroplasticity, potentially may be even more effective for long-term improved clinical outcome of schizophrenia.     

自由基代谢与精神分裂症临床症状和药物治疗的关系

目的：探讨自由基代谢与精神分裂症临床症状和药物治疗的关系。方法：是否治疗的慢性精神分裂症患者各４０例分别评定定阳性和阴性症状量表（ＰＡＮＳＳ）,并测定膜脂质过氧化物丙二醛（ＭＤＡ）含量、铜／锌超氧化物歧化酶（Ｇｕ－ＺｎＳＯＤ）和谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）活性。结果：与健康对照组相比,未治疗组患者ＭＤＡ含量和ＧＳＨ－Ｐｘ活性显著增加,治疗组患者无显著改变;而两组患者ＳＯＤ活性显著降低;未治疗     

Oxidative stress,antioxidant defenses,and schizophrenia

Schizophrenia is a complex neuropsychiatric disorder with a prevalence of nearly 1% of the world population. Accumulating evidence suggests that increase in production of reactive oxygen species (ROS) along with decrease in antioxidants and antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) may be closely associated with the pathogenesis of schizophrenia. Genes associated with glutamate transmission, dopamine transmission, synaptic plasticity, mitochondrial function, oxidative stress, lipid metabolism, and neuroinflammation have been closely linked to schizophrenia. Proteins encoded by many of the above genes affect the level of ROS, and lipid mediators that regulate signaling in the brain through cross‐talk among glutamate, dopamine, and eicosanoid receptors. Under physiological conditions, this refines the communication between neurons, glial cells and vascular cells, but in schizophrenia, the cross‐talk might initiate and promote oxidative stress‐mediated abnormal neuronal signaling responsible for symptoms of the disease.     

Intracerebroventricular ouabain administration induces oxidative stress in the rat brain

Intracerebroventricular (ICV) injection of ouabain (a potent Na⁺/K⁺-ATPase inhibitor) in rats resulted in manic-like effects. There is an emerging body of data indicating that major neuropsychiatric disorders, such as bipolar disorder and schizophrenia, are associated with increased oxidative stress. In this study, we investigated the effects of ICV ouabain injection on oxidative stress parameters in total tissue of rat brain. Our findings demonstrated that ICV injection increased thiobarbituric acid reactive species levels and protein carbonyl generation in the prefrontal cortex and hippocampus of rats. Moreover, the activity of the antioxidants enzymes catalase and superoxide dismutase was altered in several areas of the rat brain and cerebrospinal fluid of ICV ouabain-subjected rats. These results showed that Na⁺/K⁺-ATPase inhibition can lead to oxidative stress in the brain of rats.     

Serum Oxidative Stress Marker Levels in Unmedicated and Medicated Patients with Schizophrenia

Oxidative stress has been suggested to be involved in schizophrenia, but studies have demonstrated inconsistent results on oxidative stress marker level/activity in patients with schizophrenia. In order to clarify the circulating oxidative stress marker level/activity in patients with schizophrenia, this study recruited 80 schizophrenia patients (40 first-episode, drug-free and 40 chronically medicated patients) and 80 controls to analyze serum activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), and levels of lipid peroxidation marker malondialdehyde (MDA) in schizophrenia patients, and whether they associate with the severity of the disease. We showed that only serum GSH-Px activity was significantly reduced in unmedicated patients with schizophrenia when compared with control subjects, whereas the other three analyzed oxidative stress markers did not show significant differences between cases and controls. Moreover, our results demonstrated that chronic medication increased GSH-Px activity and MDA levels in patients with schizophrenia, but reduced SOD activity in the patients. We also found that short-term antipsychotic treatments on the patients with schizophrenia reduced the SOD activity. Correlation analyses indicated that the oxidative stress marker activity/level is not significantly associated with the severity of schizophrenia, except that SOD level correlated with PANSS positive score significantly. Taken together, the data from the present study suggested that the dysfunctions of oxidative stress markers in patients with schizophrenia were mainly caused by antipsychotics, emphasizing increased oxidative stress as a potential side effect of antipsychotics on the patients.     

Antioxidants are required during the early critical period, but not later, for neuronal survival

Methods for growing primary neuronal cultures rely on the inclusion of antioxidants in the culture medium, but no studies have determined precisely if or when antioxidants are required for neuronal survival, despite the significance this information would have for understanding neurodevelopment and studying oxidative stress. We show that cortical neurons grown in Neurobasal media with B27 supplement required antioxidants for only the first 24 hr post-explantation, after which the antioxidants could be removed permanently without noticeable loss of neuronal survival over the normal lifespan. Cortical cultures never exposed to antioxidants did not survive. These findings represent a novel method for substantially antioxidant-free neuronal culture, whereby antioxidants can be removed permanently from the cultures after only 1 day. This method may prove critical for studies of oxidative stress, because B27 antioxidants significantly diminished pro-oxidative effects of the excitatory neurotransmitter glutamate and hydrogen peroxide on cortical cultures, even if antioxidants were removed before the oxidizing treatment. Together, these findings suggest a brief window of high vulnerability to reactive oxygen species, and have important implications for studies of oxidative stress and developmental neuroscience.     

Superoxide anion production by neutrophils derived from peripheral blood of schizophrenic patients

Evidence indicates that excess free radicals formation may occur in patients with schizophrenia. A study comparing the production of superoxide anion by peripheral blood neutrophils of 29 schizophrenic patients with that of 17 healthy volunteers detected a significant statistical increase in superoxide anion production in schizophrenic patients compared to the healthy control group. Despite the fact that oxidative mechanisms may play a role in schizophrenia, further studies are needed to define their involvement. Such studies would shed light on the etiology and pathogenesis of schizophrenia and may lead to new therapeutic approaches using antioxidants, which might partially alleviate or prevent the symptoms of schizophrenia.     

The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids (180 mg EPA+120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.