Isoprostenes as indicators of oxidative stress in schizophrenia

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.