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Investigation of the treatment response of schizophrenia with risperidone: a pharmacogenetics study in a cohort of first episode of psychosis patients

Abstract

Psychoses characterize a group of severe and disabling mental disorders. The delay in providing adequate treatment, the duration of the first episode of psychosis (FEP) and the low response to the initial treatment are among the main factors of poor prognosis. Recently, the largest genome-wide association study (GWAS) in schizophrenia found 108 regions associated with the disease. In a previous study, our group evaluated the transcriptome and the methylome of patients in FEP before and after risperidone treatment, identifying genes that may be directly related to the response to the antipsychotic. The present study proposes the identification of genetic polymorphisms related to the response to risperidone treatment. Therefore, 210 FEP patients will be evaluated in two time points: without previous use of antipsychotic medication (baseline) and after 2 months of risperidone treatment, when they will be submitted to clinical evaluation and peripheral blood collection. To evaluate the response to risperidone, we will use the PANSS (Positive And Negative Syndrome Scale) data from the first and second interviews. The genotyping of the polymorphisms will be obtained based on data extracted from the Infinium PschArrays genomic arrays (N = 60) through bioinformatics analyses and validate the findings in the remaining sample, genotyping 150 more individuals with the PsychArray. To date, only one study has conducted a genome-wide association analysis with antipsychotic response in FEP. However, the sample size was small (N = 86) and more heterogeneous. The identification of biological response markers may, in the future, allow an early and individualized therapeutic action, reducing the duration of untreated psychosis, and offering better results in terms of reducing the morbidity and increasing the patients' quality of life. (AU)

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Scientific publications (7)
(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)
TALARICO, FERNANDA; COSTA, GIOVANY OLIVEIRA; OTA, VANESSA KIYOMI; SANTORO, MARCOS LEITE; NOTO, CRISTIANO; GADELHA, ARY; BRESSAN, RODRIGO; AZEVEDO, HATYLAS; BELANGERO, SINTIA IOLE. Systems-Level Analysis of Genetic Variants Reveals Functional and Spatiotemporal Context in Treatment-resistant Schizophrenia. Molecular Neurobiology, v. 59, n. 5, p. 13-pg., . (17/25016-8, 14/07280-1, 16/04983-7)
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; et al. Gene expression over the course of schizophrenia: from clinical high-risk for psychosis to chronic stages. NPJ SCHIZOPHRENIA, v. 5, . (14/50830-2, 11/00030-1, 14/07280-1, 10/08968-6, 17/25016-8, 16/04983-7, 11/50740-5)
HONORATO-MAUER, JESSICA; XAVIER, GABRIELA; OTA, VANESSA KIYOMI; CHEHIMI, SAMAR NASSER; MAFRA, FERNANDA; CUOCO, CASSIA; ITO, LUCAS TOSHIO; ORMOND, RAFAELLA; ASPRINO, PAULA FONTES; OLIVEIRA, ADRIELLE; et al. Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents. TRANSLATIONAL PSYCHIATRY, v. 13, n. 1, p. 9-pg., . (17/25016-8, 17/05339-7, 21/09584-1, 08/57896-8, 20/02247-7, 14/50917-0, 21/05332-8, 16/19462-2)
BELANGERO, SINTIA IOLE; OTA, VANESSA KIYOMI; GADELHA, ARY; BERBERIAN, ARTHUR ALMEIDA; DE ASSUNCAO-LEME, IDAIANE BATISTA; NOTO, CRISTIANO; CHRISTOFOLINI, DENISE MARIA; BELLUCCO, FERNANDA TEIXEIRA; SANTORO, MARCOS LEITE; MAZZOTTI, DIEGO ROBLES; et al. DGCR2 influences cortical thickness through a mechanism independent of schizophrenia pathogenesis. PSYCHIATRY RESEARCH, v. 274, p. 391-394, . (16/04983-7, 17/25016-8, 10/08968-6, 14/07280-1, 11/00030-1)
NANI, V, JOAO; DAL MAS, CAROLINE; YONAMINE, CAMILA M.; OTA, VANESSA K.; NOTO, CRISTIANO; BELANGERO, I, SINTIA; MARI, JAIR J.; BRESSAN, RODRIGO; CORDEIRO, QUIRINO; GADELHA, ARY; et al. A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 23, n. 11, p. 721-730, . (17/25016-8, 17/02413-1, 12/08941-6, 19/09207-3)
KAGAN, SIMAO; COGO-MOREIRA, HUGO; BARBOSA, MATHEUS GHOSSAIN; CAVALCANTE, DANIEL; SHINJI, ANDRE; NOTO, MARIANE; HAGUIARA, BERNARDO; CORDEIRO, QUIRINO; BELANGEIRO, SINTIA; BRESSAN, RODRIGO A.; et al. Longitudinal invariance of the positive and negative syndrome scale negative dimension in antipsychotic naive first-episode schizophrenia. EARLY INTERVENTION IN PSYCHIATRY, . (14/07280-1, 17/25016-8, 10/08968-6)
MARQUES, DIOGO FERRI; OTA, VANESSA KIYOMI; SANTORO, MARCOS LEITE; TALARICO, FERNANDA; COSTA, GIOVANY OLIVEIRA; SPINDOLA, LETICIA MARIA; COGO-MOREIRA, HUGO; CARVALHO, CAROLINA MUNIZ; XAVIER, GABRIELA; CAVALCANTE, DANIEL AZEVEDO; et al. LINE-1 hypomethylation is associated with poor risperidone response in a first episode of psychosis cohort. Epigenomics, v. 12, n. 12, . (16/04983-7, 11/50740-5, 16/02246-5, 17/25016-8, 10/08968-6, 14/07280-1)

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