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

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

Author Noto, Cristiano Autor UNIFESP Google Scholar
Ota, Vanessa Kiyomi Autor UNIFESP Google Scholar
Santoro, Marcos Leite Autor UNIFESP Google Scholar
Gouvea, Eduardo Sauerbronn Autor UNIFESP Google Scholar
Silva, Patricia Natalia Autor UNIFESP Google Scholar
Spindola, Leticia Maria Autor UNIFESP Google Scholar
Cordeiro, Quirino Autor UNIFESP Google Scholar
Bressan, Rodrigo Affonseca Autor UNIFESP Google Scholar
Gadelha, Ary Autor UNIFESP Google Scholar
Brietzke, Elisa Autor UNIFESP Google Scholar
Belangero, Sintia Iole Autor UNIFESP Google Scholar
Maes, Michael Google Scholar
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.
Keywords Schizophrenia
First-episode psychosis
Antipsychotic naive
Neuroprogression
Gene expression
Depression
Inflammation
Immune
xmlui.dri2xhtml.METS-1.0.item-coverage Totowa
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2010/08968-6
FAPESP: 2010/19176-3
FAPESP: 2011/50740-5
FAPESP: 2013/10498-6
Date 2016
Published in Molecular Neurobiology. Totowa, v. 53, n. 8, p. 5701-5709, 2016.
ISSN 0893-7648 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 5701-5709
Origin http://dx.doi.org/10.1007/s12035-015-9489-3
Access rights Closed access
Type Article
Web of Science ID WOS:000382871100054
URI https://repositorio.unifesp.br/handle/11600/57043

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