The biological connections between Attention Deficit/Hyperactivity Disorder and Major Depressive Disorder

• Grant number: 24/04362-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): May 01, 2024
• Effective date (End): February 28, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diego Luiz Rovaris
• Grantee: Nicolas Pereira Ciochetti
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/05652-0 - The physiological genomics of mental health from the perspective of the Brazilian exposome, AP.JP

Abstract

Attention deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are strongly correlated both at the epidemiological, clinical, and biological levels. ADHD exhibits one of the highest heritabilities in psychiatry, meaning that the innate biological component behind the disorder is extremely relevant to its manifestation. Conversely, MDD is a disorder with moderate heritability, meaning that besides the genetic component, exposome variables (the entirety of the non-genetic environment) have a significant influence on the disease's etiology. Additionally, MDD is extremely heterogeneous in its clinical presentation. Thus, it is possible that some subtypes of the disorder are more dependent on certain biological factors, such as susceptibility arising from genome variability, than others. Perhaps, these subtypes are precisely those that share the most biology with ADHD. In this project, we aim to study the biological relationship between ADHD and MDD using clinical and genomic data obtained from genome-wide association studies (GWAS) in two clinical samples. It is important to note that most discovery samples are essentially of European ancestry, usually collected in developed countries, resulting in a Eurocentric bias and population homogeneity in GWAS studies. Therefore, it is of utmost importance to evaluate how the environmental background of heterogeneous populations with high rates of social inequalities, such as the Brazilian population, mediates or moderates the polygenic effect on the susceptibility and severity of mental disorders. Thus, the overall objective of the Direct Doctorate project, linked to the umbrella project "The Physiological Genomics of Mental Health from the Perspective of the Brazilian Exposome," is to evaluate the molecular differences resulting in comorbidity between ADHD and MDD through comparisons with individuals who only have ADHD, individuals who only have MDD, and control individuals. Furthermore, the role of the exposome (e.g., socioeconomic level, life traumas, neurodevelopmental milestones) will be taken into consideration. (AU)