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     

The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.     

Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment

Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia, which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties. Increased levels of S100 B are associated with neurodegenerative disorders, including schizophrenia. The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum S100 B level was determined to investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cell (RBC) to oxidation were determined to investigate the oxidative status and plasma vitamin E, vitamin C, serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group. Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels. S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects. S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms. The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms.     

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.     

Reduced plasma total antioxidant status in first-episode drug-naive patients with schizophrenia

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Determination of total antioxidant status (TAS) provides an index of the sum of activities of all antioxidants. However, there have been few systematic studies to examine the relationship between TAS levels and psychopathology in first-episode and drug-naive patients with schizophrenia.TAS levels were determined in the plasma of 60 never-medicated first-episode patients with schizophrenia and 68 healthy control subjects. The schizophrenia symptomatology and the depressive symptoms were assessed by the positive and negative syndrome scale (PANSS) and the Hamilton rating scale for depression (HAMD). The results showed that TAS levels were significantly lower in first-episode patients with schizophrenia than in healthy control subjects (159.8 ± 45.8 U/ml vs 211.4 ± 46.8 U/ml, F = 39.5, df = 1, 126, p < 0.001). A trend toward significant inverse correlation between TAS levels and PANSS negative subscore was observed (r = 0.25, df = 60, p = 0.06). Our results suggest that oxidative stress occurs in an early course of schizophrenia and may have an important role in pathogenesis and perhaps, negative symptomatology of schizophrenia.     

Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia

Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia.The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively.Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6 months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder.The concentration of Trx1 in the patients with first episode of psychosis was 1.5 ± 1.0 ng/ml and 0.8 ± 0.6 ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5 ± 0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p < 0.016 and p < 0.001, respectively).Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.     

首发精神分裂症的认知功能与阴,阳性症状和抗精神病药物效应的关系

目的 探讨首发精神分裂症认知功能与阴、阳性症状和抗精神病药物效应的关系。方法 对７８例精神分裂症患者给予氯丙嗪或氯氮平治疗,于治疗前及治疗１２周末各作一次Ｗｉｓｃｏｎｓｉｎ卡片分类测验（ＷＣＳＴ）、韦氏成人智力量表（ＷＡＩＳＲ）、韦氏记忆量表（ＷＭＳ）、语言流利性测验等。另外,４５例正常人也做了上述测验。结果 首发精神分裂症患者存在广泛的认知功能障碍,上述则查结果均较正常对照组差,尤以ＷＣＳＴ明显     

Changes in oxidative stress markers in patients with schizophrenia: The effect of antipsychotic drugs

The aim of this study was to investigate the serum levels or activities of oxidative stress markers in patients with schizophrenia in acute phase and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) after treatment. We consecutively enrolled 41 patients with schizophrenia in acute phase, and 27 patients were followed up with a 4-week antipsychotic treatment. Serum oxidative stress markers were measured with assay kits. We found that Positive and Negative Syndrome Scale (PANSS) total scores were significantly negatively correlated with serum GPx activity and GSH levels and positively correlated with serum SOD activity in patients with schizophrenia in acute phase. In addition, serum GPx activity had a positive correlation with GSH levels and negative correlation with SOD activity. We also found that serum SOD activity was significantly negatively correlated with TBARS levels in patients in acute phase. Furthermore, we found significantly increased changes only in GPx activity in female patients receiving the 4-week treatment (P=0.006). In conclusion, our results suggest that SOD, GPX and GSH might be indicators of schizophrenia severity in acute phase. Furthermore, antipsychotic drugs might affect serum GPx activity in female patients receiving the 4-week treatment.     

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。     

The reduction of superoxide dismutase activity is associated with the severity of neurological soft signs in patients with schizophrenia

This study aimed to explore the relationship between antioxidant enzyme activities and neurological soft signs (NSS) in a sample of patients with schizophrenia. Sixty clinically stable patients with schizophrenia treated mostly by first-generation antipsychotics and 30 matched healthy controls were recruited. NSS were assessed in two groups by a standardized neurological examination (Krebs et al., 2000). The red blood cell (RBC) antioxidant activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were measured by spectrophotometry. RBC activities of all enzymes studied: SOD, GSH-Px and CAT, were significantly lower in the patients compared to control group. All NSS scores were significantly higher in the patients compared to healthy controls' scores. In the patients, a negative correlation was found between RBC SOD activity and NSS total score and motor coordination and motor integration sub-scores. The association between low SOD activity as a marker of oxidative stress and NSS in schizophrenic patients suggests a common pathological process of these abnormalities.