Oxidative stress in drug naive first episode psychosis and antioxidant effects of risperidone

Backgroound: Schizophrenia is accompanied by increased lipid peroxidation and nitric oxide (NO) levels and by lowered antioxidant levels. However, the effect of antipsychotic agents on these processes remains unclear. The objective of this study is to determine the oxidative stress (OS) status in drug naive first-episode psychotic patients (FEP) compared to healthy controls and to delineate the effects of risperidone on these biomarkers. Methods: 51 drug naive FEP patients and 61 healthy controls were enrolled; PEP patients were reassessed II weeks after risperidone treatment. Three OS biomarkers, i.e. lipid hydroperoxides LOOH, NO metabolites - NOx, and advanced oxidation protein products - AOPP, and two antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter TRAP, and paraoxonase 1 - PON1, were measured. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Results: Significantly lower PON1 activity and increased TRAP values were found in PEP patients. There were no significant associations between any of the OS/antioxidant biomarkers and clinical data. Risperidone treatment significantly increased PON1 activity and decreased LOOH levels. These effects of risperidone were not significantly associated with the clinical response and risperidone dosage. Discussion: Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive PEP. Risperidone may have antioxidant effects by lowering lipid peroxidation and increasing the antioxidant defenses against lipid peroxidation related to PON1. None of the biomarkers predicted treatment outcome. (C) 2015 Elsevier Ltd. All rights reserved.