Activation of the immune-inflammatory response system and the compensatory immune-regulatory system in antipsychotic naive first episode psychosis

Author(s):Show less -

Noto, Mariane Nunes ^[1] ; Maes, Michael ^[2] ; Vargas Nunes, Sandra Odebrecht ^[3] ; Ota, Vanessa Kiyomi ^[4] ; Rossaneis, Ana C. ^[5] ; Verri, Jr., Waldiceu A. ^[5] ; Cordeiro, Quirino ^[6] ; Belangero, Sintia Iole ^[4] ; Gadelha, Ary ^{[1, 7]} ; Bressan, Rodrigo Affonseca ^[2] ; Noto, Cristiano ^{[1, 7]}

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, GAPi Early Psychosis Grp, Rua Pedro de Toledo 669, 3 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[2] Chulalongkorn Univ, Dept Psychiat, Bangkok - Thailand

^[3] State Univ Londrina UEL, Hlth Sci Grad Program, Hlth Sci Ctr, Londrina - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Div Genet, Dept Morphol & Genet, Sao Paulo - Brazil

^[5] State Univ Londrina UEL, Dept Pathol, Ctr Biol Sci, Londrina - Brazil

^[6] FCMSCSP, Dept Psychiat, Sao Paulo - Brazil

^[7] Univ Fed Sao Paulo UNIFESP, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 29, n. 3, p. 416-431, MAR 2019.
• Web of Science Citations: 2

Abstract

Psychotic disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through increased levels of anti-inflammatory cytokines such as interleukin (IL)-4, IL-13 and IL-10. This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naive first episode psychosis (AN-FEP) before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-12) as compared with the CIRS response. Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement after treatment. Our findings indicate that AN-FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that (a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and (b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS might be a new drug target to treat FEP. (c) 2018 Elsevier B.V. and ECNP. All rights reserved. (AU)

• FAPESP's process: 14/07280-1 - Search for genetic markers of risk, progression and response to treatment
• Grantee: Síntia Iole Nogueira Belangero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/50740-5 - Prevention in schizophrenia and bipolar disorder from neuroscience to the community: a multiphase, multimodal and translational platform for research and intervention
• Grantee: Rodrigo Affonseca Bressan
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/08968-6 - Investigation of genetic and epigenetic markers: a translational approach for schizophrenia treatment
• Grantee: Síntia Iole Nogueira Belangero
• Support Opportunities: Regular Research Grants