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Medical treatment (olanzapine) influence on PLA2 and GSK-3b activities and gene expression in leukocytes and platelets of schizophrenic patients

Grant number: 09/05606-9
Support type:Regular Research Grants
Duration: August 01, 2009 - July 31, 2011
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Wagner Farid Gattaz
Grantee:Wagner Farid Gattaz
Home Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The present work is part of a research line entitled "Metabolism of phospholipids in neuropsychiatry diseases" carried out in Neurosciences Laboratory of the Psychiatry Faculty of University of São Paulo. Schizophrenia is a psychiatry disorder which can be observed on 1% of the world population, and it is characterized by both positive and negative symptoms. Positive symptoms include hallucinations, delusions and thought disorganization, while the negative symptoms include impaired motivation and decreased emotional expression. Two proteins should be highlighted to be used as periferic biomakers: phospholipase A2 (PLA2) and glycogen synthase kinase -3b (GSK-3b). Both proteins influence on cellular architecture and plasticity, on common metabolic ways (phospholipids metabolism and Wnt), transcription factors and gene regulation. So, the investigation about these proteins and schizophrenia is relevant to be performed. Here, the influence of medication (olanzapine, 5 to 20 mg/ day) (after three and six months) will be evaluated on the biomarkers activity: subtypes of phospholipases A2 (PLA2) and glycogen synthase kinase-3b(GSK-3b) total and phosphorylated in leukocytes and platelets of schizophrenic patients. Gene expression will be also evaluated (PLA2G2A, PLA2G1B, PLA2G2D, PLA2G4A, PLA2G6, PLA2G4B, PLA2G4C) and GSK-3b.Peripheral blood samples will be collected and analyzed before medical treatment and three and six mouths after specific treatment for each diagnosed case, in those biological matrices. Another sample, with healthy controls examined by a trained psychiatrist to exclude past and family history of psychiatric disorders, will also be studied. Statistical analyses (t-Student test and ANOVA) will be undertaken to verify the olanzapine influence on these biomarkers activities and gene expression. Novel values and correlations between these enzymes / proteins and schizophrenia are expected as key contributing results. (AU)