High predictive value of immune-inflammatory biomarkers for schizophrenia diagnosis and association with treatment resistance

Abstract

Objectives. 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.

Key words::

• schizophrenia
• cytokines
• neuroinflammation
• chemokines
• treatment resistance

Acknowledgements

The authors are thankful to the patients, their families, and healthy volunteers.

Statement of Interest

RAB has received research funding from Fundação Safra, Fundação ABADS, Janssen, Eli Lilly, Lundbeck, Novartis and Roche, has served as a speaker for Astra Zeneca, Bristol, Janssen, Lundbeck and Revista Brasileira de Psiquiatria, and is a shareholder of Radiopharmacus Ltda and Biomolecular Technology Ltda. AG was on the speakers’ bureau and/or has acted as a consultant for Janssen-Cilag in the last 12 months. The other authors have no conflicts of interest to disclose.

Funding

CN has received PhD scholarships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). MM is supported by a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) PVE fellowship at the Health Sciences Graduate Program, Universidade Estadual de Londrina (UEL). VKO has received PhD scholarship from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, 2010/19176-3). AG has received research support from CNPq. RAB and EB are supported by FAPESP, CNPq, and CAPES.