Evaluation of differential extracellular vesicule miRNA expression associated with the emergence of psychiatric symptoms in adolescents

• Grant number: 20/02247-7
• Support type: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2020
• Effective date (End): March 31, 2022
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Marcos Leite Santoro
• Grantee: Jessica Honorato Mauer
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Psychiatric disorders (PDs) are one of the main causes of life years lost due to disability (DALYs - Disability-Adjusted Life Years). Symptoms usually start during late childhood and adolescence, and may persist during adulthood. PDs have a complex and multifactorial inheritance with influence of genetic and environmental factors. As PDs are complex diseases, longitudinal approaches are necessary to understand how genetic risk interacts with environmental factors. Genetic expression and DNA methylation studies are particularly important to understand longitudinal changes (before and after the onset of psychiatric symptoms), though, with the limitation of access to the target tissue, the brain. Exosomes are small extracellular vesicles (30-100 nm in diameter) which are secreted by many cell types and detected in different body fluids (e.g. serum, saliva, urine). Exosomes represent their cell type of origin, having specific membrane proteins and intracellular content, including miRNAs. Due to their size, exosomes are capable of crossing the blood-brain barrier and, for this reason, they have been studied in neurological and psychiatric diseases with the purpose of identifying potential biomarkers. In this study, we aim to evaluate the serum extracellular vesicule-derived miRNA expression of adolescents before and after the development of PDs. In this way, 125 individuals from the Brazilian High Risk Cohort (BHRC) will be selected, from which 25 will be controls (without diagnosis and family history of PDs) and 100 will be individuals who transited to psychiatric disorders over the course of the BHRCS. The BHRCS includes 2500 families (1000 randomly selected from the population and 1500 with risk for PDs) and is a longitudinal study focused on improving the understanding of brain development and mental health of children and adolescents. The study has three timepoints: baseline (2010) with children 6 to 12 years old; first follow-up (2014) with individuals 9 to 17 years old; second follow-up (2019) with adolescents 14 to 23 years old. With the current study, we hope to identify potential biomarkers of transition to PDs and improve the current prediction methods for PDs. (AU)