Depression, Cytokine, and Cytokine by Treatment Interactions Modulate Gene Expression in Antipsychotic Naive First Episode Psychosis

Author(s):Show less -

Noto, Cristiano ; Ota, Vanessa Kiyomi ; Santoro, Marcos Leite ; Gouvea, Eduardo Sauerbronn ; Silva, Patricia Natalia ; Spindola, Leticia Maria ; Cordeiro, Quirino ; Bressan, Rodrigo Affonseca ; Gadelha, Ary ; Brietzke, Elisa ; Belangero, Sintia Iole ; Maes, Michael

• Document type: Journal article
• Source: Molecular Neurobiology; v. 53, n. 8, p. 5701-5709, OCT 2016.
• Web of Science Citations: 20

Abstract

In schizophrenia, genetic and environmental factors affect neurodevelopment and neuroprogressive trajectory. Altered expression of neuro-immune genes and increased levels of cytokines are observed, especially in patients with comorbid depression. However, it remains unclear whether circulating levels of cytokines and expression of these genes are associated, and how antipsychotic treatments impact this association. Relationships between messenger RNA (mRNA) expression of 11 schizophrenia-related genes and circulating levels of cytokines (interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha) were analyzed in 174 antipsychotic na < ve first episode psychosis (FEP) and in 77 healthy controls. A subgroup of 72 patients was reassessed after treatment with risperidone. FEP patients were divided into those with and without depression. FEP patients with depression showed increased COMT expression and decreased NDEL1 expression. Increased IL-6 was associated with lowered AKT1 and DROSHA expression, while increased IL-10 was associated with increased NDEL1, DISC1, and MBP expression. IL-6 levels significantly increased the risperidone-induced expression of AKT1, DICER1, DROSHA, and COMT mRNA. The differential mRNA gene expression in FEP is largely associated with increased cytokine levels. While increased IL-6 may downregulate AKT-mediated cellular functions and dysregulate genes involved in microRNA (miRNA) machinery, increased IL-10 has neuroprotective properties. Increased IL-6 levels may prime the expression of genes (AKT1, DICER1, DROSHA, and COMT) in response to risperidone, suggesting that cytokine x treatment x gene interactions may improve cell function profiles. FEP patients with depression show a different gene expression profile reinforcing the theory that depression in FEP is a different phenotype. (AU)

• 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
• 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: 13/10498-6 - Machine learning in neuroimaging: development of methods and clinical applications in psychiatric disorders
• Grantee: João Ricardo Sato
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/19176-3 - Gene expression and DNA methylation analysis in drug-naive first episode of psychosis patients
• Grantee: Vanessa Kiyomi Ota Kuniyoshi
• Support Opportunities: Scholarships in Brazil - Doctorate