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GENE EXPRESSION AND DNA METHYLATION ANALYSES IN DRUG-NAIVE FIRST EPISODE OF PSYCHOSIS PATIENTS

Grant number: 10/19176-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2011
Effective date (End): March 31, 2015
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Síntia Iole Nogueira Belangero
Grantee:Vanessa Kiyomi Ota Kuniyoshi
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):13/11781-3 - Functional analysis of MBD5 gene: characterization of the biological role of a gene in neurodevelopment, BE.EP.DR

Abstract

Schizophrenia is the most severe and disabling mental disorder among psychiatric disorders. In addition, the delay in providing appropriate treatment and the duration of the first episode of psychosis are among the main factors of poor prognosis. The project proposes the investigation of genetic and epigenetic markers for the treatment of schizophrenia by studying the expression and methylation pattern neurotransmitters receptors and regulators genes. In this study, 50 patients with first episode psychosis without using medication will be submitted to clinical assessment and collection of peripheral blood at diagnosis and two months after the start of treatment and 50 control subjects. DNA and RNA will be extracted after the blood collection and the study of gene expression will be performed by PCR array, investigating the expression of 84 neurotransmitters receptors and regulators genes. Genes differentially expressed between cases and controls or before and after treatment are selected and investigated for DNA methylation by Methylation Specific PCR technique Real Time. The results of this study may provide new data on the gene expression and epigenetic regulation involved in psychosis itself as well as in relation to pharmacological response. The identification of biological markers for both psychosis and for treating schizophrenia will allow an early and individual therapeutic action and reduction of untreated psychosis time, which will result in decreased morbidity and a higher quality of life for patients.

Scientific publications (8)
(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)
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. Depression, Cytokine, and Cytokine by Treatment Interactions Modulate Gene Expression in Antipsychotic Naive First Episode Psychosis. Molecular Neurobiology, v. 53, n. 8, p. 5701-5709, OCT 2016. Web of Science Citations: 20.
NOTO, CRISTIANO; OTA, VANESSA KIYOMI; GADELHA, ARY; NOTO, MARIANE NUNES; BARBOSA, DECIO SABBATINI; BONIFACIO, KAMILA LANDUCCI; NUNES, SANDRA ODEBRECHT; CORDEIRO, QUIRINO; BELANGERO, SINTIA IOLE; BRESSAN, RODRIGO AFFONSECA; MAES, MICHAEL; BRIETZKE, ELISA. Oxidative stress in drug naive first episode psychosis and antioxidant effects of risperidone. JOURNAL OF PSYCHIATRIC RESEARCH, v. 68, p. 210-216, SEP 2015. Web of Science Citations: 20.
BRINHOLI, FRANCIS FREGONESI; NOTO, CRISTIANO; MAESA'D, MICHAEL; BONIFACIO, KAMILA LANDUCCI; BRIETZKE, ELISA; OTA, VANESSA KIYOMI; GADELHA, ARY; CORDEIRO, QUIRINO; BELANGERO, SINTIA IOLE; BRESSAN, RODRIGO AFFONSECA; VARGAS, HEBER ODEBRECHT; HIGACHI, LUCIANA; DE FARIAS, CARINE CONEGLIAN; MOREIRA, ESTEFANIA GASTALDELLO; BARBOSA, DECIO SABBATINI. Lowered paraoxonase 1 (PON1) activity is associated with increased cytokine levels in drug naive first episode psychosis. SCHIZOPHRENIA RESEARCH, v. 166, n. 1-3, p. 225-230, AUG 2015. Web of Science Citations: 9.
NOTO, CRISTIANO; OTA, VANESSA KIYOMI; SANTORO, MARCOS LEITE; ORTIZ, BRUNO B.; RIZZO, LUCAS B.; HIGUCHI, CINTHIA HIROKO; CORDEIRO, QUIRINO; BELANGERO, SINTIA IOLE; BRESSAN, RODRIGO AFFONSECA; GADELHA, ARY; MAES, MICHAEL; BRIETZKE, ELISA. Effects of depression on the cytokine profile in drug naive first-episode psychosis. SCHIZOPHRENIA RESEARCH, v. 164, n. 1-3, p. 53-58, MAY 2015. Web of Science Citations: 23.
NOTO, CRISTIANO; MAES, MICHAEL; OTA, VANESSA KIYOMI; TEIXEIRA, ANTONIO LUCIO; BRESSAN, RODRIGO AFFONSECA; GADELHA, ARY; BRIETZKE, ELISA. High predictive value of immune-inflammatory biomarkers for schizophrenia diagnosis and association with treatment resistance. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, v. 16, n. 6, p. 422-429, 2015. Web of Science Citations: 22.
SANTORO, MARCOS LEITE; GADELHA, ARY; OTA, VANESSA K.; CUNHA, GRACCIELLE R.; ASEVEDO, ELSON; NOTO, CRISTIANO S.; SPINDOLA, LETICIA M.; PAN, PEDRO M.; TALARICO, FERNANDA; MANSUR, RODRIGO B.; SILVA, PATRICIA N.; BRIETZKE, ELISA; CORDEIRO, QUIRINO; BRESSAN, RODRIGO A.; BELANGERO, SINTIA IOLE. Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, v. 16, n. 6, p. 441-446, 2015. Web of Science Citations: 6.
OTA, VANESSA KIYOMI; NOTO, CRISTIANO; GADELHA, ARY; SANTORO, MARCOS LEITE; SPINDOLA, LETICIA MARIA; GOUVEA, EDUARDO SAUERBRONN; STILHANO, ROBERTA SESSA; ORTIZ, BRUNO BERTOLUCCI; SILVA, PATRICIA NATALIA; SATO, JOAO RICARDO; HAN, SANG WON; CORDEIRO, QUIRINO; BRESSAN, RODRIGO AFFONSECA; BELANGERO, SINTIA IOLE. Changes in gene expression and methylation in the blood of patients with first-episode psychosis. SCHIZOPHRENIA RESEARCH, v. 159, n. 2-3, p. 358-364, NOV 2014. Web of Science Citations: 22.
OTA, VANESSA KIYOMI; NOTO, CRISTIANO; GADELHA, ARY; SANTORO, MARCOS LEITE; ORTIZ, BRUNO BERTOLUCCI; ANDRADE, ELVIS HENRIQUE; TASSO, BRAZILIO CARVALHO; NERY SPINDOLA, LETICIA MARIA; SILVA, PATRICIA NATALIA; ABILIO, VANESSA COSTHEK; CARDOSO SMITH, MARILIA DE ARRUDA; SATO, JOAO RICARDO; BRIETZKE, ELISA; CORDEIRO, QUIRINO; BRESSAN, RODRIGO AFFONSECA; BELANGERO, SINTIA IOLE. Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: A follow-up study in antipsychotic-naive patients with first-episode psychosis. JOURNAL OF PSYCHIATRIC RESEARCH, v. 56, p. 130-136, SEP 2014. Web of Science Citations: 12.

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