Biomarkers of treatment naive psychosis

• Grant number: 14/50830-2
• Support type: Regular Research Grants
• Duration: April 01, 2015 - March 31, 2016
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Cooperation agreement: CONFAP ; Newton Fund, with FAPESP as a partner institution in Brazil ; MRC, UKRI
• Principal researcher: Rodrigo Affonseca Bressan
• Grantee: Rodrigo Affonseca Bressan
• Principal researcher abroad: Gerome Breen
• Institution abroad: King's College London, England
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The investiqation of individuais during their first-episode psychosis (FEP) before the proqression of the disorder and particularly before treatment with antipsychotic medications is helpful for understanding the complexity of schizophrenia. Several studies suggested that gene expressron in blood could serve as a diagnosis tool for brain-related diseases. Considering that schizophrenia is a chronic condiction that requires a lifelong treatment, disease progression and use of antipsychotic medication can confound results on gene expression and DNA methylation. Our main aim of this study is to identify genetic markers using genomic, transcriptomic and methylomic approaches in a longitudinal cohort of FEP. The patients will be assessed in the baseline, all antipsychotic naive, (anFEP, N=80), and after eight weeks (FEP-8w, N=80) and one year (FEP-1Y, N=30) of antipsychotic treatment. Until this moment, we collected and isolated the mRNA and the DNA of more than 75 anFEP, 75 FEP-8w and 20 FEP-1Y. The remaining patients will be collected during the first semester of this Project. The DNA Genotyping array will be performed in Brazil using the PsychChip array with a GWAS core backbone and specific content from the Psychiatric Genomics Consortium, under the hypothesis that gene expression and methylation differences for FEP individuals and for treatment response are determined by genetic variance. Transcriptomic and methylomic approaches will be performed in UK. For the whole gene expression arrays we are going to use the "HumanHT -12 v4 Expresston BeadChip". witch provides genome-wide transcriptional coverage of well-characterized genes (approx. 25,000 genes). Concerning DNA methylation analysis, we will generate data using the lnfinium Human Methylation 450 BeadChip, which interrogates more than 485,000 methylation sites per sample. With these data, we expect to find potential blood biomarkers for disease and for treatment response (anFEP x FEP-8w and FEP-1 Y). Moreover, we will hold an advanced course in bioinformatics focusing on gene expression and methylation analysis at UNIFESP lasting a week. This will be available to 30 PhD students of São Paulo State with no charge. The analysis course will be leaded by Dr. Breen’s team. This Project is a great opportunity for both sides. Dr. Breen will contribute with this expertise in bioinformatics and will analyze the “big data” generated by transcriptome and methylome analysis. Moreover, his team will teach for a grad students about this analysis. Thus, we would be able to perform it by ourselves. On the other hand, the Brazilian group will contribute with a unique anFEP cohort including a multimodal assessment, besides expertise and background in genomic and epigenomic techniques. Both sites will contribute equally to the Project performance, helping to find out genetic markers to schizophrenia. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OTA, VANESSA KIYOMI; MORETTI, PATRICIA NATALIA; SANTORO, MARCOS LEITE; TALARICO, FERNANDA; SPINDOLA, LETICIA MARIA; XAVIER, GABRIELA; CARVALHO, CAROLINA MUNIZ; MARQUES, DIOGO FERRI; COSTA, GIOVANY OLIVEIRA; PELLEGRINO, RENATA; DE JONG, SIMONE; CORDEIRO, QUIRINO; HAKONARSON, HAKON; BREEN, GEROME; NOTO, CRISTIANO; BRESSAN, RODRIGO AFFONSECA; GADELHAZ, ARY; MARI, JAIR DE JESUS; BELANGERO, I, SINTIA. Gene expression over the course of schizophrenia: from clinical high-risk for psychosis to chronic stages. NPJ SCHIZOPHRENIA, v. 5, MAR 28 2019. Web of Science Citations: 2.

SANTORO, MARCOS LEITE; OTA, VANESSA; DE JONG, SIMONE; NOTO, CRISTIANO; SPINDOLA, LETICIA M.; TALARICO, FERNANDA; GOUYEA, EDUARDO; LEE, SANG HYUCK; MORETTI, PATRICIA; CURTIS, CHARLES; PATEL, HAMEL; NEWHOUSE, STEPHEN; CARYALHO, CAROLINA MUNIZ; GADELHA, ARY; CORDEIRE, QUIRINO; BRESSAN, RODRIGO AFFONSECA; BELANGERO, SINTIA IOLE; BREEN, GEROME. Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort. TRANSLATIONAL PSYCHIATRY, v. 8, AUG 31 2018. Web of Science Citations: 6.

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GOUVEA, E. S.; OTA, V. K.; NOTO, C.; SANTORO, M. L.; SPINDOLA, L. M.; MORETTI, P. N.; CARVALHO, C. M.; XAVIER, G.; RIOS, A. C.; SATO, J. R.; HAYASHI, M. A. F.; BRIETZKE, E.; GADELHA, A.; BRESSAN, R. A.; CORDEIRO, Q.; BELANGERO, S. I. Gene expression alterations related to mania and psychosis in peripheral blood of patients with a first episode of psychosis. TRANSLATIONAL PSYCHIATRY, v. 6, OCT 4 2016. Web of Science Citations: 9.