title: Lowered paraoxonase 1 (PON1) activity is associated with increased cytokine levels in drug naïve first episode psychosis.
abstract: BACKGROUND
  Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naïve first episode psychosis (FEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels.
  
  
  METHODS
  A total of 51 drug-naïve FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-α and activity of PON1 were quantified.
  
  
  RESULTS
  Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-α. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-α. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile).
  
  
  CONCLUSIONS
  The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10. It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies FEP and that increased cytokine levels may further modulate PON1 activity.
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Francis Fregonesi
authors.initials: FF
authors.lastname: Brinholi
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil; First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP,Brazil. Electronic address: csnoto@gmail.com.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Kamila Landucci
authors.initials: KL
authors.lastname: Bonifácio
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil; First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP,Brazil.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Sintia Iole
authors.initials: SI
authors.lastname: Belangero
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Heber Odebrecht
authors.initials: HO
authors.lastname: Vargas
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Higachi
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Carine Coneglian
authors.initials: CC
authors.lastname: de Farias
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Estefânia Gastaldello
authors.initials: EG
authors.lastname: Moreira
authors.affiliation: Graduation Program in Health Sciences, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Décio Sabbatini
authors.initials: DS
authors.lastname: Barbosa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D012559:Schizophrenia / Q000097:blood* / Q000201:enzymology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Cytokines; Drug naïve; First episode psychosis (FEP); Oxidative stress; Paraoxonase (PON1); Schizophrenia