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

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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

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 53, n. 8, p. 5701-5709, OCT 2016.
• Citações Web of Science: 20

Resumo

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)

• Processo FAPESP: 10/08968-6 - Investigação de marcadores genéticos e epigenéticos: uma abordagem translacional para o tratamento de esquizofrenia
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/50740-5 - Prevenção na esquizofrenia e no transtorno bipolar da neurociência à comunidade: uma plataforma multifásica, multimodal e translacional para investigação e intervenção
• Beneficiário: Rodrigo Affonseca Bressan
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/10498-6 - Aprendizado de máquina em neuroimagem: desenvolvimento de métodos e aplicações clínicas em transtornos psiquiátricos
• Beneficiário: João Ricardo Sato
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/19176-3 - Análise de expressão gênica e metilação de DNA de pacientes em primeiro episódio psicótico virgens de tratamento
• Beneficiário: Vanessa Kiyomi Ota Kuniyoshi
• Modalidade de apoio: Bolsas no Brasil - Doutorado