非酶类抗氧化物与双相障碍的关系研究进展北大核心CSCD

双相障碍影响着世界上约3%的人口,是导致精神残疾和自杀死亡的主要原因[1]。双相障碍具有反复发作的特点,并且能够造成患者情绪、行为及生物节律的异常和认知功能的损害[2]。目前双相障碍的确切病因尚不清楚,其诊断与检测缺乏特异性生物学标记物。相关研究表明,氧化应激在精神疾病尤其是双相障碍的病理过程中起着重要作用[3-5]。非酶类抗氧化物包括尿酸、胆红素和白蛋白,这三种代谢产物可以作为反映机体氧化应激水平的标记物,其血清浓度或与双相障碍发病存在关联[6,7]。我们拟就氧化应激导致双相障碍患者尿酸、胆红素和白蛋白的变化进行综述。     

微RNA在精神分裂症发病机制中的作用研究进展

关于微RNA(miRNA)对精神分裂症的发病机制的研究已成为热门的研究方向之一。本研究就目前国内外已发表的研究进行综述。     

首发未服药精神分裂症患者血浆非酶抗氧化物浓度分析

目的探讨首发未服药精神分裂症患者血浆非酶抗氧化物水平及其与临床特征间的关系。方法测定55例首发未服用抗精神病药精神分裂症患者和42名正常对照的血浆非酶抗氧化物水平,包括白蛋白、总胆红素浓度和尿酸浓度;采用阳性和阴性症状量表(positive and negative symptoms scale,PANSS)评定精神症状。结果患者组血浆白蛋白和尿酸浓度明显低于对照组[(44.72±3.42)g/Lvs(46.70±3.43)g/L,(3.11±1.00)×102μmoL/Lvs(5.00±1.01)×102μmoL/L,P均小于0.05];以阳性症状为主的患者血浆总胆红素浓度明显高于以阴性症状为主的患者[(12.48±3.86)μmoL/L vs(10.27±1.78)μmoL/L,P=0.04];男性患者尿酸浓度明显高于女性患者[(3.54±1.21)×102μmoL/L vs(2.88±0.76)×102μmoL/L,P=0.01];对照组男女性之间上述3个指标的差异均无统计学意义(P>0.05);相关分析仅发现对照组血浆白蛋白、尿酸与年龄相关(r=-0.39,P=0.01;r=-0.40,P=0.01)...     

线粒体动力学紊乱在精神分裂症中作用的研究进展

线粒体是细胞的能量加工厂，线粒体代谢与线粒体动力学密切相关。研究表明线粒体动 力学障碍在神经发育中有重要的影响，与精神分裂症紧密相关。本文就动力学异常与神经发育及精神 分裂症的相关性作一综述。     

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...     

精神分裂症阴性症状发病机制及治疗的研究进展

精神分裂症分为阳性症状和阴性症状,目前多数药物对于阳性症状的治疗疗效明显好于阴性症状的疗效.临床上,阴性症状主要是指正常的心理功能的消失或下降,如意志力减弱,内向孤僻,言语思维贫乏,冷漠,是最难消除的精神分裂症症状,甚至某些药物治疗可加重阴性症状.目前研究已发现多个神经递质可能参与了精神分裂症阴性症状的发病过程,如多巴胺（DA）受体、去甲肾上腺素、5-羟色胺（5-HT）受体等,同时还有很多非神经递质类因素与阴性症状有关.现将精神分裂症阴性症状的可能发病机制和治疗进展逐一阐述.     

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。     

创伤性脑损伤后精神分裂症发病风险的研究进展

已知创伤性脑损伤会引起多种精神障碍的发生,其中创伤性脑损伤与精神分裂症之间的关系仍不明确。现对创伤性脑损伤后精神分裂症发病的风险、影响因素及机制方面的研究进展进行系统综述,进一步明确创伤性脑损伤与精神分裂症的关系,对创伤性脑损伤后精神分裂症的预防、治疗、预后等具有重要意义。     

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     

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。     

线粒体功能障碍与精神分裂症关系研究进展

精神分裂症是一种复杂的神经精神性疾病,发病机制涉及神经化学、神经发育等因素。有证据表明在对精神分裂症患者脑部研究中可观察到由线粒体功能障碍导致的病理变化,最近发现精神分裂症断裂基因（Disrupted—in—Schizophrenia1,DISC1）存在于线粒体中,可以确定线粒体与精神分裂症发病存在某种联系。     

吸烟对男性精神分裂症患者临床症状的影响及可能机制

目的探讨吸烟对男性精神分裂症患者临床症状的影响及氧化应激在精神分裂症高吸烟率中的作用。方法研究共入组男性精神分裂症患者130例,根据目前的吸烟状况分吸烟组（74例）和非吸烟组（56侧）,运用阳性和阴性症状量表（PANSS）评定精神病理症状;采用分光光度法检测其血浆超氧化物岐化酶（SOD）、过氧化氢酶（CAT）活性以及丙二醛（MDA）浓度。结果（1）吸烟组PANSS阳性症状（14．5±6．3）分显著低于非吸烟组（17．5±4．9）分（P〈0．05）;吸烟组患者吸烟数量与PANSS阴性症状分显著负相关（r=-0．23,P=0．02）。（2）血浆CAT活性吸烟组（2．9±0．3）×10^3U／L显著高于非吸烟组（1．6±0．2）×10^3U／L,吸烟患者血浆SOD活性与吸烟数量显著相关（r=0．24,P=0．04）;血浆MDA浓度吸烟组（9．2±0．7）mmol／L显著低于非吸烟7组（14．4±1．7）mmol／L。结论男性精神分裂症患者的吸烟可能通过缓解氧化应激来改善部分精神病理症状。     

Mitochondrial dysfunction in schizophrenia: Pathways,mechanisms and implications

Mitochondria play a critical role in regulating cellular functions including bioenergetics, calcium homeostasis, redox signalling, and apoptotic cell death. Mitochondria are also essential to many aspects of neurodevelopment and neuronal functions. However, mitochondrial impairment may affect bioenergetics in the developing brain and alter critical neuronal processes leading to neurodevelopmental abnormalities.Schizophrenia is a chronic and severe neuropsychiatric disorder of neurodevelopmental origin. Immuno-inflammatory pathway is one of the widely appreciated mechanisms that has consistently been implicated in the neurodevelopmental origin of schizophrenia. However, the source of inflammation and the underlying neurobiological mechanisms leading to schizophrenia are yet to be fully ascertained. Recent understanding reveals that perturbation of mitochondrial network dynamics might lead to various nervous system disorders with inflammatory pathologies. Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuroprogressive changes in schizophrenia. Herein, we summarise the current understanding of molecular links between mitochondrial dysfunctions and pathogenesis of schizophrenia based on evidence from genomics, proteomics and imaging studies, which together support a role for mitochondrial impairment in the pathogenetic pathways of schizophrenia.     

Anxiety comorbidity in schizophrenia

Diagnostic and treatment hierarchical reductionisms have led to an oversight of anxiety syndromes in schizophrenia. Nevertheless, recent data have indicated that anxiety can be a significant source of morbidity in this patient group. This paper reviews current knowledge concerning anxiety comorbidity in schizophrenia, its epidemiology, course, and treatment. A computerized search of the literature published from 1966 to July 2012 was conducted on Medline. Comorbid anxiety disorders are present in 38.3% of subjects with schizophrenia spectrum disorders. The most common anxiety disorder is social phobia followed by post-traumatic stress disorder and obsessive compulsive disorder. The presence and severity of symptoms of anxiety are associated with more severe clinical features and poorer outcomes. Available literature on the treatment consists primarily of case reports and open trials. Fragments of data support the notion of treating these anxiety states and syndromes as co-occurring clinical conditions with adjunctive medications and psychosocial interventions. However, additional work remains to be done on this issue before firm conclusions can be drawn.     

Prenatal exposure to cigarette smoke causes persistent changes in the oxidative balance and in DNA structural integrity in rats submitted to the animal model of schizophrenia

Epidemiological studies have indicated that prenatal exposure to environmental insults can bring an increased risk of schizophrenia. The objective of our study was to determine biochemical parameters in rats exposed to cigarette smoke (CS) in the prenatal period, evaluated in adult offspring submitted to animal model of schizophrenia induced by acute subanaesthetic doses of ketamine (5 mg/kg, 15 mg/kg and 25 mg/kg). Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day, daily for a period of 28 days. We evaluated the oxidative damage in lipid and protein in the rat brain, and DNA damage in the peripheral blood of male adult offspring rats. To determine oxidative damage in the lipids, we measured the formation of thiobarbituric acid reactive species (TBARS) and the oxidative damage to the proteins was assessed by the determination of carbonyl groups content. We also evaluated DNA damage using single-cell gel electrophoresis (comet assay). Our results showed that rats exposed to CS in the prenatal period presented a significant increase of the lipid peroxidation, protein oxidation and DNA damage in adult age. We can observe that the animals submitted at acute doses of ketamine also presented an increase of the lipid peroxidation and protein oxidation at different doses and structures. Finally, we suggest that exposure to CS during the prenatal period affects two essential cerebral processes during development: redox regulation and DNA integrity, evaluated in adult offspring. These effects can leads to several neurochemical changes similar to the pathophysiology of schizophrenia.     

Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine

Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal’s locomotion. This study showed that the administration of folic acid over 7 days was unable to prevent hyper locomotion. In contrast, folic acid (10 and 50 mg/kg) administrated over a period of 14 days, was able to partially prevent the hyper locomotion. Our data indicates that both acute and chronic administrations of ketamine increased the time to first contact between the animals, while the increased latency for social contact was completely prevented by folic acid (5, 10 and 50 mg/kg). Chronic and acute administrations of ketamine also increased lipid peroxidation and protein carbonylation in brain. Folic acid (10 and 50 mg/kg) supplements showed protective effects on the oxidative damage found in the different brain structures evaluated. All together, the results indicate that nutritional supplementation with folic acid provides promising results in an animal model of schizophrenia induced by ketamine.     

Increased systemic oxidatively generated DNA and RNA damage in schizophrenia

Schizophrenia is associated with a substantially increased somatic morbidity and mortality, which may partly be caused by accelerated cellular aging. Oxidative stress is an established mediator of aging and a suggested aetiological mechanism in both schizophrenia and age-related medical disorders such as cardiovascular disease, type 2 diabetes and dementia. We determined the urinary excretion of markers of systemic Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) oxidation, 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, respectively, in 40 schizophrenia patients and 40 age- and sex-matched controls, using ultra-performance liquid chromatography with tandem mass spectrometry. Measures of psychopathology, perceived stress and cortisol secretion were collected. Patients were re-examined after four months. We found a 20% increase in the median excretion of both markers in schizophrenia patients vs. healthy controls (P=0.003 and <0.001, respectively). This difference persisted after the adjustment for multiple demographical, lifestyle and metabolic factors. In patients, the marker excretion was not influenced by medication load, and was not driven by symptom severity, perceived stress or cortisol secretion, neither at baseline nor in relation to changes at follow-up. We conclude that schizophrenia is associated with increased systemic nucleic acid damage from oxidation, which could constitute a molecular link between schizophrenia and its associated signs of accelerated aging.     

Inflammation in schizophrenia: A question of balance

In the past decade, there has been renewed interest in immune/inflammatory changes and their associated oxidative/nitrosative consequences as key pathophysiological mechanisms in schizophrenia and related disorders. Both brain cell components (microglia, astrocytes, and neurons) and peripheral immune cells have been implicated in inflammation and the resulting oxidative/nitrosative stress (O&NS) in schizophrenia. Furthermore, down-regulation of endogenous antioxidant and anti-inflammatory mechanisms has been identified in biological samples from patients, although the degree and progression of the inflammatory process and the nature of its self-regulatory mechanisms vary from early onset to full-blown disease. This review focuses on the interactions between inflammation and O&NS, their damaging consequences for brain cells in schizophrenia, the possible origins of inflammation and increased O&NS in the disorder, and current pharmacological strategies to deal with these processes (mainly treatments with anti-inflammatory or antioxidant drugs as add-ons to antipsychotics).