Objective: The level of various specific biomarkers of oxidative stress in plasma from schizophrenic patients, as well as biomarkers (the level of isoprostanes) in urine in schizophrenic patients was described. The aim of our present study was to evaluate biomarkers of oxidative stress by oxidative/nitrative modifications of plasma proteins (by measuring the level of carbonyl groups and 3-nitrotyrosine in proteins) from patients with schizophrenic disorders and from control group. We also investigated the level of low-molecular-weight thiols [glutathione (GSH), cysteine (CSH), cysteinylglycine (CGSH) and homocysteine] in plasma obtained from schizophrenic patients and from healthy volunteers. Patients hospitalized in the 1st and 2nd Psychiatric Department of the Medical University in Lodz, Poland were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other extrapyramidal syndromes). According to DSM-IV criteria, all patients had a diagnosis of paranoid type. They were treated with antipsychotic drugs (clozapine, risperidone, olanzapine). The mean duration of schizophrenia was about 5 years. Methods: Levels of carbonyl groups and 3-nitrotyrosine residues in plasma proteins were measured by ELISA and a competition ELISA, respectively. High-performance liquid chromatography was used to analyze free thiols in plasma. Results: We observed a statistically increased level of biomarkers of oxidative/nitrative stress such as carbonyl groups or 3-nitrotyrosine in plasma proteins from schizophrenic patients. In schizophrenic patients the amount of homocysteine in plasma was higher compared with the control group; the level of GSH, CSH and CGSH was decreased. This indicates that reactive oxygen species and reactive nitrogen species may stimulate oxidative/nitrative modifications of plasma proteins in schizophrenic patients. Conclusion: Considering the data presented in this study, we suggest that the amount of carbonyl groups and 3-nitrotyrosine in plasma proteins may be important indicators of protein damage in vivo in schizophrenia.

Oxidative stress in blood platelets is observed in various diseases, including neuropsychiatric disorders. The aim of our study was to evaluate oxidative stress in blood platelets from patients with schizophrenic disorders by measuring the activity of the platelet antioxidative enzyme, superoxide dismutase (SOD), concomitant with the level of thiobarbituric acid reactive species (TBARS). In blood platelets obtained from schizophrenic patients (with paranoid schizophrenia according to DSM-IV criteria) and from healthy volunteers the level of reactive oxygen species was also measured via chemiluminescence. In resting blood platelets from schizophrenic patients the chemiluminescence was higher than in platelets from control subjects (P < 0.05), but in thrombin-activated platelets an increase (about 53%) of chemiluminescence was observed, however this increase was lower than in thrombin-stimulated platelets from healthy subjects (101.5%). The results indicate that in platelets from schizophrenic patients generation of reactive oxygen species is enhanced. Moreover, we observed that SOD activity in blood platelets from schizophrenic patients was significantly lower than in control platelets and that a correlation exists between increased lipid peroxidation and inhibition of the activity of this antioxidative enzyme in schizophrenic platelets.

The mechanisms of oxidative stress in schizophrenic patients are not fully understood. In the present study, we investigated the effect of elevated level of homocysteine (Hcys) on some parameters of oxidative stress, namely thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation in plasma, the level of carbonyl groups in plasma proteins, as well as the amount of 3-nitrotyrosine in plasma proteins isolated from schizophrenic patients. Patients hospitalised in I and II Psychiatric Department of Medical University in Lodz, Poland were interviewed with special questionnaire (treatment, course of diseases, dyskinesis and other EPS). According to DSM-IV criteria all patients had diagnosis of paranoid type. They were treated with antipsychotic drugs (clozapine, risperidone, olanzapine). Mean time of schizophrenia duration was about 5 years. High-performance liquid chromatography was used to analyse the total level of homocysteine in plasma. Levels of carbonyl groups and 3-nitrotyrosine residues in plasma proteins were measured by ELISA and a competition ELISA, respectively. The lipid peroxidation in plasma was measured by the level of TBARS. Our results showed that in schizophrenic patients the amount of homocysteine in plasma was higher in comparison with the control group. We also observed a statistically increased level of biomarkers of oxidative/nitrative stress such as carbonyl groups or 3-nitrotyrosine in plasma proteins from schizophrenic patients. Moreover, our experiments indicate that the correlation between the increased amount of homocysteine and the oxidative stress exists. Considering the data presented in this study, we suggest that the elevated Hcys in schizophrenic patients may stimulate the oxidative stress.

Objectives Platelets, the smallest anucleated blood cells, play an essential role in the first step of complex haemostatic process. This review presents the haemostatic function of blood platelets related to their activation in psychiatric disorders (schizophrenia, depression), the role of antipsychotic and antidepressant medication, and introduces the mechanisms by which activated platelets may be involved in the pathophysiology of these disorders. Methods Platelets are interesting and easily accessible blood cells to study biochemical pathways related to schizophrenia and other psychiatric disorders, and their complex activation process might be useful as a diagnostic peripheral marker for studying psychiatric disorders and haemostatic complications. Results The excessive activation of platelets observed in patients with depression and schizophrenia is involved in cardiovascular diseases, stroke and increased risk of thrombotic complications that may be major causes of morbidity and mortality of patients. The use of antidepressants or antipsychotic drugs in depression and schizophrenia treatment is often associated with haematological side effects such as bleeding, venous thromboembolism and impaired platelet function. Conclusions Understanding the role of platelet activation in psychiatric disorders such as schizophrenia or depression and medication may improve therapies in the future.

Aims:  There is evidence that dysregulation of free radicals metabolism associated with abnormal activities of antioxidative enzymes in schizophrenia can lead to lipid peroxidation in plasma, erythrocytes, blood platelets and cerebrospinal fluid. Injury to neurons in schizophrenia may affect their function, i.e. membrane transport, impairment of energy production in mitochondria, changes in membrane phospholipid composition, alteration of receptors and transporters as well as neurotransmission. The purpose of the present study was to assess the total antioxidant capacity (TAC) and lipid peroxidation (expressed as the level of thiobarbituric acid reactive substances [TBARS]) in plasma from schizophrenic patients taking olanzapine or risperidone. The level of TBARS estimated according to the Rice–Evans method and TAC ([ABTS; 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) radical cation decolorization assay]) in plasma from schizophrenic patients (DSM‐IV criteria for schizophrenia, n = 30, age 18–36) taking olanzapine or risperidone and from healthy volunteers (n = 30) were measured.Methods:  The level of TBARS in plasma from healthy volunteers after incubation with olanzapine or risperidone was also estimated.Results:  Significantly lower plasma TAC (P < 0.05) and significantly increased level of TBARS (P < 0.001) in schizophrenic patients were observed. The in vitro study showed that after olanzapine or risperidone (at final concentrations corresponding to doses used in acute episodes of schizophrenia treatment) no changes of plasma lipid peroxidation were found (P > 0.05). The obtained results indicate that the pro‐oxidant disturbances occur in schizophrenic patients (acute episode) taking stable doses of olanzapine or risperidone.Conclusion:  It seems that second‐generation antipsychotics (olanzapine and risperidone) are not responsible for increase of plasma lipid peroxidation.

Free radicals induce oxidative stress and damage to all types of biological molecules and may be involved in pathology of schizophrenia. A cell membrane dysfunction caused by lipid peroxidation can be secondary to a free radical-mediated pathology and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. The aim of our study was to estimate oxidative stress in a group of schizophrenic patients by using different biomarkers of free radicals-induced lipid peroxidation (isoprostanes, thiobarbituric acid reactive substances (TBARS)). We also determined the products of enzymatic peroxidation of arachidonic acid, such as thromboxane B2 (TXB2) and its metabolite 11-dehydrothromboxane B2. Isoprostanes (IPs) are a family of novel prostaglandin isomers and are produced in free radical-catalysed reactions from arachidonic acid. They are useful as a specific, sensitive, chemically stable, noninvasive index of free radical generation in vivo. We therefore assessed in schizophrenic patients and control subjects the level of urinary excretion of isoprostane--8-epi-prostaglandin F2 alpha, (8-isoPGF2 alpha)--a marker of lipid peroxidation induced by free radicals using an immunoassay kit. We also studied the level of the other marker of enzymatic arachidonic acid peroxidation--11-dehydrothromboxane B2--in urine from schizophrenic patients and healthy volunteers. Moreover, we estimated the production of TBARS and TXB2 in plasma from schizophrenic patients and the control group. Patients hospitalised in the II Psychiatric Department of Medical University in Lodz, Poland, were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other EPS). According to DSM-IV criteria, all patients had diagnosis of paranoid type. All patients were treated with second-generation antipsychotic drugs (risperidone, clozapine, and olanzapine). Mean time of schizophrenia duration was about 2 years. We observed a statistically increased level of TBARS in plasma (P=0.000162) and isoprostanes (P=3.5 x 10(-12)) in urine of schizophrenic patients in comparison with the control group. The level of markers of enzymatic oxidation of arachidonic acid (TXB2 and its metabolite, 11-dehydrothromboxane B2) did not change. This indicates that free radicals induce peroxidation of unsaturated fatty acid in schizophrenic patients. Considering the data presented in this study, we suggest that non-invasive measurement of 8-isoPGF2 alpha, is a valuable and sensitive (contrary to TBARS) indicator of oxidative stress status in vivo in schizophrenia.