title: Oxidative stress in drug naïve first episode psychosis and antioxidant effects of risperidone.
abstract: BACKGROUND
  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 naïve 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; FEP patients were reassessed 11 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 FEP 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.
  
  
  CONCLUSIONS
  Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive FEP. 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.
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, Brazil.
authors.forename: Mariane Nunes
authors.initials: MN
authors.lastname: Noto
authors.affiliation: Health Sciences Graduate Program, Health Sciences Center, State University of Londrina (UEL), Brazil.
authors.forename: Décio Sabbatini
authors.initials: DS
authors.lastname: Barbosa
authors.affiliation: Health Sciences Graduate Program, Health Sciences Center, State University of Londrina (UEL), Brazil.
authors.forename: Kamila Landucci
authors.initials: KL
authors.lastname: Bonifácio
authors.affiliation: Health Sciences Graduate Program, Health Sciences Center, State University of Londrina (UEL), Brazil.
authors.forename: Sandra Odebrecht
authors.initials: SO
authors.lastname: Nunes
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, Brazil.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Sintia Iole
authors.initials: SI
authors.lastname: Belangero
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Health Sciences Graduate Program, Health Sciences Center, State University of Londrina (UEL), Brazil; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: elisabrietzke@hotmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D015415:Biomarkers; D018967:Risperidone
keywords: Antioxidant; Antipsychotic; Drug naïve; First-episode psychosis; Oxidative stress; Schizophrenia