Search for genetic markers of risk, progression and response to treatment

• Grant number: 14/07280-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2015
• End date: August 31, 2017
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Síntia Iole Nogueira Belangero
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ary Gadelha de Alencar Araripe Neto ; Elisa Brietzke ; Eurípedes Constantino Miguel Filho ; Jair de Jesus Mari ; João Ricardo Sato ; Luis Augusto Paim Rohde ; Marilia de Arruda Cardoso Smith ; Patrícia Natália Silva Moretti ; Quirino Cordeiro Júnior ; Rodrigo Affonseca Bressan ; Sang Won Han

Abstract

Schizophrenia is currently seen as a disease of neurodevelopment that determines high rates of morbidity and mortality. Only prevention strategies, including identification of risk factors and early intervention may reduce these rates. This project focuses on identifying genetic markers of risk, progression and response to treatment to promote primary, secondary, tertiary schizophrenia prevention and incorporating a platform for genetic investigation of individuals in several disease states: a) children at risk to develop mental disorder; b) ultra high risk subjects (UHR); c) first-episode psychosis (PEP) subjects; and d) patients with schizophrenia. The modules described below are designed in order to investigate individuals in these four phases of pre-illness and disease. Some of these cohorts will be followed longitudinally. The cell module includes telomeric measures as markers of aging and disease progression. The genomic/variants module includes identification of polymorphisms, mutations and CNVs in both large scale and in specific genes. The transcriptional module compass expression analysis including large-scale and specific genes. The epigenomic module includes DNA methylation analysis and miRNAs expression. Finally, the function module is proposed to investigate the functional role of variants potentially related to disease and response to treatment in vitro. This study represents a break in the current dichotomy between normality and disease, using several stages of the disease, as well as various clinical sub-phenotypes to be studied with different genetic approaches. This platform is innovative because it allows generating hypotheses with focus on identification of genetic risk factors in various stages of the disease and that, in future, may be tested for prevention interventions in schizophrenia. (AU)

Scientific publications

(23)

(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)

SPINDOLA, LETICIA M.; SANTORO, MARCOS L.; PAN, PEDRO M.; OTA, VANESSA K.; XAVIER, GABRIELA; CARVALHO, CAROLINA M.; TALARICO, FERNANDA; SLEIMAN, PATRICK; MARCH, MICHAEL; PELLEGRINO, RENATA; et al. Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths. CLINICAL EPIGENETICS, v. 11, n. 1, OCT 21 2019. (16/04983-7, 14/50917-0, 15/10733-0, 16/25374-9, 17/05339-7, 14/07280-1)

MAURYA, PAWAN KUMAR; RIZZO, LUCAS BORTOLOTTO; XAVIER, GABRIELA; TEMPAKU, PRISCILA FARIAS; ZENI-GRAIFF, MAIARA; SANTORO, MARCOS L.; MAZZOTTI, DIEGO ROBLES; ZUGMAN, ANDRE; PAN, PEDRO; NOTO, CRISTIANO; et al. Shorter leukocyte telomere length in patients at ultra high risk for psychosis. European Neuropsychopharmacology, v. 27, n. 5, p. 538-542, MAY 2017. (14/07280-1)

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.; et al. 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. (11/50740-5, 14/50830-2, 12/12686-1, 13/10498-6, 10/08968-6, 14/07280-1)

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, MAR 28 2019. (14/50830-2, 11/00030-1, 14/07280-1, 10/08968-6, 17/25016-8, 16/04983-7, 11/50740-5)

MAURYA, PAWAN KUMAR; RIZZO, LUCAS BORTOLOTTO; XAVIER, GABRIELA; TEMPAKU, PRISCILA FARIAS; OTA, VANESSA KIYOMI; SANTORO, MARCOS L.; SPINDOLA, LETICIA M.; MORETTI, PATRICIA S.; MAZZOTTI, DIEGO R.; GADELHA, ARY; et al. Leukocyte telomere length variation in different stages of schizophrenia. JOURNAL OF PSYCHIATRIC RESEARCH, v. 96, p. 218-223, JAN 2018. (10/08968-6, 14/07280-1)

NOTO, MARIANE NUNES; MAES, MICHAEL; VARGAS NUNES, SANDRA ODEBRECHT; OTA, VANESSA KIYOMI; ROSSANEIS, ANA C.; VERRI, JR., WALDICEU A.; CORDEIRO, QUIRINO; BELANGERO, SINTIA IOLE; GADELHA, ARY; BRESSAN, RODRIGO AFFONSECA; et al. Activation of the immune-inflammatory response system and the compensatory immune-regulatory system in antipsychotic naive first episode psychosis. European Neuropsychopharmacology, v. 29, n. 3, p. 416-431, MAR 2019. (14/07280-1, 11/50740-5, 10/08968-6)

DE ARAUJO, CELIA MARIA; ZUGMAN, ANDRE; SWARDFAGER, WALTER; NOGUEIRA BELANGERO, SINTIA IOLE; OTA, VANESSA KIYOMI; SPINDOLA, LETICIA MARIA; HAKONARSON, HAKON; PELLEGRINO, RENATA; GADELHA, ARY; SALUM, GIOVANNI ABRAHAO; et al. Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence. JOURNAL OF PSYCHIATRIC RESEARCH, v. 98, p. 51-58, MAR 2018. (13/08531-5, 14/07280-1, 14/50917-0)

DE MOURA, ADRIANA MIYAZAKI; LOPEZ PINAYA, WALTER HUGO; GADELHA, ARY; ZUGMAN, ANDRE; NOTO, CRISTIANO; CORDEIRO, QUIRINO; BELANGERO, SINTIA IOLE; JACKOWSKI, ANDREA P.; BRESSAN, RODRIGO A.; SATO, JOAO RICARDO. Investigating brain structural patterns in first episode psychosis and schizophrenia using MRI and a machine learning approach. PSYCHIATRY RESEARCH-NEUROIMAGING, v. 275, p. 14-20, MAY 30 2018. (13/10498-6, 13/08531-5, 14/07280-1, 13/05168-7)

REBELLO, KEILA; MOURA, LUCIANA M.; XAVIER, GABRIELA; SPINDOLA, LETICIA M.; CARVALHO, CAROLINA MUNIZ; HOEXTER, MARCELO QUEIROZ; GADELHA, ARY; PICON, FELIPE; PAN, PEDRO MARIO; ZUGMAN, ANDRE; et al. Association between spontaneous activity of the default mode network hubs and leukocyte telomere length in late childhood and early adolescence. JOURNAL OF PSYCHOSOMATIC RESEARCH, v. 127, DEC 2019. (13/08531-5, 18/21934-5, 14/50917-0, 14/07280-1, 18/04654-9)

SPINDOLA, LETICIA M.; SANTORO, MARCOS L.; PAN, PEDRO M.; OTA, VANESSA K.; XAVIER, GABRIELA; CARVALHO, CAROLINA M.; TALARICO, FERNANDA; SLEIMAN, PATRICK; MARCH, MICHAEL; PELLEGRINO, RENATA; et al. Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths. CLINICAL EPIGENETICS, v. 11, n. 1, p. 16-pg., 2019-10-21. (15/10733-0, 17/05339-7, 16/04983-7, 14/50917-0, 14/07280-1, 16/25374-9)

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., 2022-03-12. (17/25016-8, 14/07280-1, 16/04983-7)

COIMBRA, BRUNO MESSINA; CARVALHO, CAROLINA MUNIZ; MORETTI, PATRICIA NATALIA; MELLO, MARCELO FEIJO; BELANGERO, SINTIA I.. Stress-related telomere length in children: A systematic review. JOURNAL OF PSYCHIATRIC RESEARCH, v. 92, p. 47-54, SEP 2017. (14/07280-1, 14/12559-5)

MORETTI, PATRICIA N.; OTA, VANESSA K.; GOUVEA, EDUARDO S.; PEDRINI, MARIANA; SANTORO, MARCOS L.; TALARICO, FERNANDA; SPINDOLA, LETICIA M.; CARVALHO, CAROLINA MUNIZ; NOTO, CRISTIANO; XAVIER, GABRIELA; et al. Accessing Gene Expression in Treatment-Resistant Schizophrenia. Molecular Neurobiology, v. 55, n. 8, p. 7000-7008, AUG 2018. (14/07280-1, 12/12669-0, 11/50740-5)

TRUBETSKOY, VASSILY; PARDINAS, ANTONIO F.; QI, TING; PANAGIOTAROPOULOU, GEORGIA; AWASTHI, SWAPNIL; BIGDELI, TIM B.; BRYOIS, JULIEN; CHEN, CHIA-YEN; DENNISON, CHARLOTTE A.; HALL, LYNSEY S.; et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature, v. 604, n. 7906, p. 24-pg., 2022-04-08. (14/07280-1, 10/08968-6, 11/50740-5)

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, APR 2020. (16/04983-7, 11/50740-5, 16/02246-5, 17/25016-8, 10/08968-6, 14/07280-1)

DE ARAUJO, CELIA MARIA; SWARDFAGER, WALTER; ZUGMAN, ANDRE; COGO-MOREIRA, HUGO; BELANGERO, SINTIA I.; OTA, VANESSA K.; SPINDOLA, LETICIA M.; HAKONARSON, HAKON; PELLEGRINO, RENATA; GADELHA, ARY; et al. Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?. CNS SPECTRUMS, v. 25, n. 6, p. 790-796, DEC 2020. (14/07280-1, 13/08531-5, 16/04983-7, 14/50917-0)

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, JUL 2021. (14/07280-1, 17/25016-8, 10/08968-6)

OTA, VANESSA KIYOMI; SANTORO, MARCOS LEITE; SPINDOLA, LETICIA MARIA; PAN, PEDRO MARIO; SIMABUCURO, ANDRESSA; XAVIER, GABRIELA; VIEIRA-FONSECA, TAMIRIS; ZANARDO, EVELIN ALINE; CAMARGO DOS SANTOS, FELIPE RODOLFO; SCHAFER, JULIA LUIZA; et al. Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents. TRANSLATIONAL PSYCHIATRY, v. 10, n. 1, MAR 17 2020. (16/04983-7, 08/57896-8, 14/50917-0, 14/07280-1, 17/05339-7)

TALARICO, FERNANDA; SANTORO, MARCOS; OTA, VANESSA K.; GADELHA, ARY; PELLEGRINO, RENATA; HAKONARSON, HAKON; BRESSAN, RODRIGO; MARI, JAIR J.; BELANGERO, SINTIA. Implications of an admixed Brazilian population in schizophrenia polygenic risk score. SCHIZOPHRENIA RESEARCH, v. 204, p. 404-406, FEB 2019. (14/07280-1, 10/08968-6, 16/04983-7, 11/50740-5, 17/20059-0)

SANTORO, MARCOS LEITE; OTA, VANESSA; DE JONG, SIMONE; NOTO, CRISTIANO; SPINDOLA, LETICIA M.; TALARICO, FERNANDA; GOUYEA, EDUARDO; LEE, SANG HYUCK; MORETTI, PATRICIA; CURTIS, CHARLES; et al. 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. (14/50830-2, 14/07280-1, 14/22223-4, 12/12686-1, 10/08968-6, 16/13737-0, 16/04983-7, 11/50740-5)

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, APR 2019. (16/04983-7, 17/25016-8, 10/08968-6, 14/07280-1, 11/00030-1)

CARVALHO, CAROLINA MUNIZ; PAN, PEDRO M.; OTA, VANESSA K.; SPINDOLA, LETICIA M.; XAVIER, GABRIELA; SANTORO, MARCOS L.; MAZZOTTI, DIEGO R.; PELLEGRINO, RENATA; HAKONARSON, HAKON; ROHDE, LUIS AUGUSTO; et al. Effects of the interaction between genetic factors and maltreatment on child and adolescent psychiatric disorders. PSYCHIATRY RESEARCH, v. 273, p. 575-577, MAR 2019. (08/57896-8, 14/50917-0, 14/07280-1)

ASSUNCAO-LEME, IDAIANE BATISTA; ZUGMAN, ANDRE; DE MOURA, LUCIANA MONTEIRO; SATO, JOAO RICARDO; HIGUCHI, CINTHIA; ORTIZ, BRUNO BERTOLUCCI; NOTO, CRISTIANO; OTA, VANESSA KIYOMI; BELANGERO, SINTIA IOLE; BRESSAN, RODRIGO A.; et al. Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?. CNS SPECTRUMS, v. 26, n. 5, p. 545-549, OCT 2021. (14/07280-1, 10/08968-6)