title: High predictive value of immune-inflammatory biomarkers for schizophrenia diagnosis and association with treatment resistance.
abstract: OBJECTIVE
  Recent schizophrenia (SCZ) research aims to establish biomarkers with high predictive value for the diagnosis, severity of illness or treatment resistance. SCZ is accompanied by activated immune-inflammatory pathways, including increased levels of cytokines and chemokines, but few studies tried to identify predictive properties of such measures.
  
  
  METHODS
  We included 54 medicated SCZ patients and 118 healthy controls and examined 15 cytokines and chemokines. Possible associations between these immune-inflammatory biomarkers and the diagnosis of SCZ, severity of illness and treatment resistance were investigated.
  
  
  RESULTS
  SCZ is associated with a specific cytokine - chemokine profile, i.e., increased CCL11, MIP-1α, sTNF-R1 and sTNF-R2 levels, and decreased levels of IP-10, TNF-α, IL-2 and IL-4. The combination of five biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of SCZ with a sensitivity of 70.0% and a specificity of 89.4%. There was a weak association between the negative symptoms and biomarkers, i.e., IL-2 (inversely) and CCL11 (positively). Patients with treatment resistance showed increased levels of sTNF-R1, sTNF-R2 and MCP-1.
  
  
  CONCLUSIONS
  The findings of this study reinforce that SCZ is associated with a pro-inflammatory profile and suggest that some immune mediators may be used as reliable biomarkers for the diagnosis of SCZ and treatment resistance.
authors.affiliation: a LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de São Paulo (UNIFESP) , Brazil.|b First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP) , São Paulo , Brazil.|c Programa de Esquizofrenia (PROESQ), Universidade Federal de São Paulo (UNIFESP) , Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: d Department of Psychiatry , Chulalongkorn University , Bangkok , Thailand.|e Health Sciences Graduate Program, Health Sciences Center, State University of Londrina (UEL) , Brazil.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: a LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de São Paulo (UNIFESP) , Brazil.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: f Translational Psychoneuroimmunology Group, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: a LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de São Paulo (UNIFESP) , Brazil.|c Programa de Esquizofrenia (PROESQ), Universidade Federal de São Paulo (UNIFESP) , Brazil.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: a LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de São Paulo (UNIFESP) , Brazil.|c Programa de Esquizofrenia (PROESQ), Universidade Federal de São Paulo (UNIFESP) , Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: a LiNC-Interdisciplinary Laboratory of Clinical Neuroscience, Universidade Federal de São Paulo (UNIFESP) , Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
keywords: chemokines; cytokines; neuroinflammation; schizophrenia; treatment resistance