Impact of genetic variants on structural neuroimaging: a longitudinal approach in psychiatric disorders

• Grant number: 22/15880-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): June 01, 2023
• Effective date (End): March 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcos Leite Santoro
• Grantee: Lucas Toshio Ito
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/05332-8 - Brazilian high-risk cohort for psychiatric disorders: 10 years follow-up, AP.TEM

Abstract

Psychiatric disorders (PD) are one of the main causes of years lost due to disability due to their early onset and severity of symptoms, which can persist and impact mental health until adulthood. Thus, projects dedicated to studying the etiology and pathophysiology of PDs since childhood have the potential to enable preventive approaches and generate ideas for new therapeutics procedures. Genome-wide association studies (GWAS) allowed the identification of genome variants (SNVs) related to several PDs and from them it was possible to explore and understand part of the genetic factors of these diseases. Among these SNVs, there are many that exert lasting influences on brain structures and functions, acting on the development of PDs, however it is still a challenge to identify and understand the way these variants act in the associated regions. By identifying these intermediate factors that are closer to the genetic effect, it would be possible to explore new approaches aimed at preventing and treating PDs. Our hypothesis is that the SNVs previously associated with PDs in the GWAS studies may act in a individual or joint way in structural neuroimaging alterations, as they are frequently associated with PDs. Thus, we aim to verify the relationship between SNVs associated with psychiatric disorders, the development of these diseases and structural changes in specific brain regions over time. Our study will use longitudinal data from the Brazilian High Risk Cohort Study for Psychiatric Disorders (BHRCS), which is a cohort of children and adolescents with genetic and neuroimaging data collected in three timepoints (baseline and 3/7-years follow-up) and with a new phase in progress (10-year follow-up). In this project, we will initially use 362 probands, which are those who already have genetic data and at least two neuroimaging measurements over a period of more than 5 years, and later we will add the probands with neuroimaging measurements from the new phase. With this, through a longitudinal analysis, we will observe the influence of SNVs throughout the individual's development and how they act at a structural level in the brain, where we hope to observe a direct and indirect influence on the development of PDs. (AU)