Study of epigenetic alterations in GABAergic neurotransmission in schizophrenia and other psychoses and in animals undergoing social isolation from weaning

• Grant number: 15/02948-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2015
• End date: May 31, 2018
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Cristina Marta Del-Ben
• Grantee: Helene Aparecida Fachim
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants, AP.TEM
• Associated scholarship(s): 17/00624-5 - DNA methylation investigation in first episode of psychosis and in rats undergoing isolation rearing from weaning in the two major excitatory and inhibitory systems, BE.EP.PD

Abstract

A large body of evidence suggests that schizophrenia is a disease which occurs during the development of central nervous system (CNS) which results from the combination of both genetic and environmental factors. Several studies have shown that GABAergic neurotransmission is affected in this disease, among these abnormalities there is a decrease in reelin, parvalbumin and GAD67 levels. These changes have been found in both postmortem human brain and in animal models of the disease. Despite the significant efforts of several areas of research, little progress has been made in understanding the genetic and environmental basis of schizophrenia. Thus epigenetic mechanisms seem to be excellent targets to the study of the aetiology of psychosis. Furthermore, the translational study will allow improved workability of new treatment strategies. Despite this evidence, little is known about the levels of methylation of promoter regions of gene encoding these proteins both in the disease and in the animal models also the reduction in the expression thereof occurs due to hypermethylation of the promoter region of these genes. The aim of this study is to evaluate the occurrence of hypermethylation in the promoter regions of the genes which encode the proteins reelin, parvalbumin and GAD67, in both peripheral blood samples of patients after the first psychotic episode, and in blood samples and also brain tissue of animals undergoing social isolation from weaning.

Scientific publications

(11)

(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)

LOUREIRO, CAMILA MARCELINO; DA ROZA, DAIANE LEITE; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; FACHIM, HELENE APARECIDA; SIMOES-AMBROSIO, LIVIA MARIA CORDEIRO; DEMINICE, RAFAEL; JORDAO, ALCEU AFONSO; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA; et al. Plasma amino acids profile in first-episode psychosis, unaffected siblings and community-based controls. SCIENTIFIC REPORTS, v. 10, n. 1, DEC 8 2020. (13/11167-3, 16/12195-9, 18/07581-2, 17/00624-5, 15/02948-7, 19/13229-2)

FACHIM, HELENE A.; CORSI-ZUELLI, FABIANA; LOUREIRO, CAMILA M.; IAMJAN, SRI-ARUN; SHUHAMA, ROSANA; JOCA, SAMIA; MENEZES, PAULO ROSSI; HEALD, ADRIAN; LOUZADA-JUNIOR, PAULO; DALTON, CAROLINE F.; et al. Early-life stress effects on BDNF DNA methylation in first-episode psychosis and in rats reared in isolation. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 108, JUN 8 2021. (12/05178-0, 12/17626-7, 13/11167-3, 17/00624-5, 13/08216-2, 19/13229-2, 17/17480-6, 15/02948-7)

LOUREIRO, CAMILA M.; FACHIM, HELENE A.; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; MENEZES, PAULO R.; DALTON, CAROLINE F.; DEL-BEN, CRISTINA M.; REYNOLDS, GAVIN P.; LOUZADA-JUNIOR, PAULO. The relationship of childhood trauma and DNA methylation of NMDA receptor genes in first-episode schizophrenia. Epigenomics, v. 13, n. 12, p. 927-937, JUN 2021. (12/05178-0, 13/11167-3, 17/00624-5, 16/12195-9, 19/13229-2, 15/02948-7, 13/08216-2)

LOUREIRO, CAMILA MARCELINO; CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; SHUHAMA, ROSANA; DE SOUZA CHAGAS, NATALIA MOTA; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA; LOUZADA-JUNIOR, PAULO. Plasma prevalence of anti-N-methyl-d-aspartate receptor IgG antibodies in early stages of psychosis. Ciênc. saúde coletiva, v. 26, n. 3, p. 1085-1094, MAR 2021. (17/17480-6, 13/08216-2, 13/11167-3, 17/00624-5, 16/12195-9, 12/05178-0, 15/02948-7)

FACHIM, HELENE A.; LOUREIRO, CAMILA M.; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; LOUZADA, JR., PAULO; MENEZES, PAULO ROSSI; DALTON, CAROLINE F.; DEL-BEN, CRISTINA MARTA; REYNOLDS, GAVIN P.. GRIN2B promoter methylation deficits in early-onset schizophrenia and its association with cognitive function. Epigenomics, v. 11, n. 4, p. 401-410, MAR 2019. (12/05178-0, 12/17626-7, 16/12195-9, 13/11167-3, 13/08216-2, 17/17480-6, 15/02948-7)

FACHIM, HELENE A.; SRISAWAT, UMARAT; DALTON, CAROLINE F.; HARTE, MICHAEL K.; MARSH, SAMUEL; NEILL, JOANNA C.; REYNOLDS, GAVIN P.. Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain. Epigenomics, v. 8, n. 9, p. 1179-1183, SEP 2016. (15/02948-7)

CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; BERTOZI, GIULIANO; JOCA, SAMIA REGIANE LOURENGO; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain. FRONTIERS IN NEUROSCIENCE, v. 12, JAN 11 2019. (13/11167-3, 13/08216-2, 17/00624-5, 16/12195-9, 15/02948-7, 17/17480-6, 12/05178-0)

LOUREIRO, CAMILA MARCELINO; FACHIM, HELENE APARECIDA; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; JOCA, SAMIA; MENEZES, PAULO ROSSI; DALTON, CAROLINE F.; DEL-BEN, CRISTINA MARTA; LOUZADA-JUNIOR, PAULO; REYNOLDS, GAVIN P.. Epigenetic-mediated N-methyl-D-aspartate receptor changes in the brain of isolated reared rats. Epigenomics, v. 12, n. 22, NOV 2020. (13/08216-2, 16/12195-9, 12/05178-0, 13/11167-3, 12/17626-7, 15/02948-7, 19/13229-2, 17/00624-5)

CORSI-ZUELLI, FABIANA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; FACHIM, HELENE APARECIDA; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; MONDELLI, VALERIA; DEL-BEN, CRISTINA MARTA. Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment. PSYCHOLOGICAL MEDICINE, v. 50, n. 7, p. 1139-1147, MAY 2020. (12/05178-0, 16/12195-9, 13/11167-3, 13/08216-2, 17/17480-6, 15/02948-7)

CAMILA MARCELINO LOUREIRO; FABIANA CORSI-ZUELLI; HELENE APARECIDA FACHIM; ROSANA SHUHAMA; ADRIELLE MARTINS DE OLIVEIRA; PAULO ROSSI MENEZES; CAROLINE F. DALTON; PAULO LOUZADA-JUNIOR; SINTIA IOLE BELANGERO; FERNANDA COELI-LACCHINI; et al. Lifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM study. Revista Brasileira de Psiquiatria, v. 45, n. 3, p. 226-235, 2023-07-03. (12/05178-0, 19/13229-2, 17/00624-5, 15/02948-7, 20/15752-1, 13/08216-2, 21/07448-3, 13/11167-3)

LOUREIRO, CAMILA MARCELINO; CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; SHUHAMA, ROSANA; DE SOUZA CHAGAS, NATALIA MOTA; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA; LOUZADA-JUNIOR, PAULO. Plasma prevalence of anti-N-methyl-d-aspartate receptor IgG antibodies in early stages of psychosis. Ciênc. saúde coletiva, v. 26, n. 3, p. 10-pg., 2021-03-01. (15/02948-7, 17/17480-6, 12/05178-0, 13/11167-3, 13/08216-2, 16/12195-9, 17/00624-5)