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

Author(s):Show less -

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

Affiliation

^[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

• Document type: Journal article
• Source: NPJ SCHIZOPHRENIA; v. 5, MAR 28 2019.
• Web of Science Citations: 2

Abstract

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)

• 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 type: Research Projects - Thematic Grants
• FAPESP's process: 14/50830-2 - Biomarkers of treatment naive psychosis
• Grantee: Rodrigo Affonseca Bressan
• Support type: Regular Research 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 type: Regular Research Grants
• FAPESP's process: 17/25016-8 - INVESTIGATION OF THE TREATMENT RESPONSE OF SCHIZOPHRENIA WITH RISPERIDONE: A PHARMACOGENETICS STUDY IN A COHORT OF FIRST EPISODE OF PSYCHOSIS PATIENTS
• Grantee: Síntia Iole Nogueira Belangero
• Support type: Regular Research Grants
• FAPESP's process: 14/07280-1 - Search for genetic markers of risk, progression and response to treatment
• Grantee: Síntia Iole Nogueira Belangero
• Support type: Regular Research Grants
• FAPESP's process: 16/04983-7 - Neuroimaging, genomics, transcriptomics and epigenomics: dealing with big data toward an integrative model of mental disorders
• Grantee: Jair de Jesus Mari
• Support type: Research Grants - eScience and Data Science Program - Regular Program Grants
• FAPESP's process: 11/00030-1 - Association study of endocannabinoid system and schizophrenia
• Grantee: Síntia Iole Nogueira Belangero
• Support type: Regular Research Grants