Gene expression over the course of schizophrenia: from clinical high-risk for psychosis to chronic stages

Autor(es):Mostrar menos -

Ota, Vanessa Kiyomi ^{[1, 2, 3]} ; Moretti, Patricia Natalia ^{[4, 1, 2, 3]} ; Santoro, Marcos Leite ^{[1, 2, 3]} ; Talarico, Fernanda ^{[1, 2, 3]} ; Spindola, Leticia Maria ^{[1, 2, 3]} ; Xavier, Gabriela ^{[1, 2]} ; Carvalho, Carolina Muniz ^{[1, 2, 3]} ; Marques, Diogo Ferri ^{[1, 2, 3]} ; Costa, Giovany Oliveira ^{[1, 2, 3]} ; Pellegrino, Renata ^[5] ; de Jong, Simone ^[6] ; Cordeiro, Quirino ^[7] ; Hakonarson, Hakon ^[5] ; Breen, Gerome ^[6] ; Noto, Cristiano ^{[2, 3]} ; Bressan, Rodrigo Affonseca ^{[2, 3]} ; Gadelhaz, Ary ^{[2, 3]} ; Mari, Jair de Jesus ^{[2, 3]} ; Belangero, I, Sintia

Afiliação do(s) autor(es)

^[1] I, Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Disciplina Genet, Sao Paulo - Brazil

^[2] I, Univ Fed Sao Paulo UNIFESP, Dept Psiquiatria, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo - Brazil

^[3] I, Univ Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo - Brazil

^[4] Univ Brasilia UNB, Fac Med, Brasilia, DF - Brazil

^[5] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA

^[6] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London - England

^[7] Santa Casa Sch Med Sci, Dept Psiquiatria, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NPJ SCHIZOPHRENIA; v. 5, MAR 28 2019.
• Citações Web of Science: 2

Resumo

The study of patients with schizophrenia (SZ) at different clinical stages may help clarify what effects could be due to the disease itself, to the pharmacological treatment, or to the disease progression. We compared expression levels of targeted genes in blood from individuals in different stages of SZ: clinical high risk for psychosis (CHR), first episode of psychosis (FEP), and chronic SZ (CSZ). Then, we further verified whether single-nucleotide polymorphisms (SNPs) could be related to gene expression differences. We investigated 12 genes in 394 individuals (27 individuals with CHR, 70 antipsychotic-naive individuals with FEP, 157 CSZ patients, and 140 healthy controls (HCs)). For a subsample, genotype data were also available, and we extracted SNPs that were previously associated with the expression of selected genes in whole blood or brain tissue. We generated a mediation model in which a putative cause (SNP) is related to a presumed effect (disorder) via an intermediate variable (gene expression). MBP and NDEL1 were upregulated in FEP compared to all other groups; DGCR8 was downregulated in FEP compared to HC and CHR; DGCR2 was downregulated in CSZ compared to FEP and HCs; DISC1 was upregulated in schizophrenia compared to controls or FEP, possibly induced by the rs3738398 and rs10864693 genotypes, which were associated with DISC1 expression; and UFD1 was upregulated in CSZ and CHR compared to FEP and HC. Our results indicated changes in gene expression profiles throughout the different clinical stages of SZ, reinforcing the need for staging approaches to better capture SZ heterogeneity. (AU)

• Processo FAPESP: 14/50830-2 - Biomarcadores genéticos em pacientes com psicose virgens de tratamento
• Beneficiário: Rodrigo Affonseca Bressan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/00030-1 - Estudo de associação de genes do sistema endocanabinóide e esquizofrenia
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/07280-1 - Busca por marcadores genéticos de risco, de progressão e de reposta ao tratamento na esquizofrenia
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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: 17/25016-8 - Investigação da resposta ao tratamento da esquizofrenia com risperidona: estudo farmacogenético em uma coorte de pacientes em primeiro episódio psicótico
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/04983-7 - Neuroimagem, genômica, transcriptômica e epigenômica: conduzindo análises em larga escala em direção a um modelo integrativo de transtornos mentais
• Beneficiário: Jair de Jesus Mari
• Modalidade de apoio: Auxílio à Pesquisa - Programa eScience e Data Science - 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