Investigation of Genetic Variants Associated with Risperidone Response in Autism Spectrum Disorder

• Grant number: 25/02652-2
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Aline Cristiane Planello
• Grantee: Aline Cristiane Planello
• Host Institution: Faculdade de Medicina de Jundiaí (FMJ). Jundiaí , SP, Brazil
• City of the host institution: Jundiaí
• Associated researchers: Marcelo Rocha Marques ; Nilva de Karla Cervigne

Abstract

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition involving multiple genetic pathways. Pharmacogenomics (PGx) has explored how genetic variants modulate drug response in complex conditions such as ASD. Risperidone, one of the few medications approved for managing behavioral symptoms in ASD, shows substantial interindividual variability in therapeutic response, partly attributed to polymorphisms in genes related to the drug's pharmacokinetics and pharmacodynamics. This study aims to investigate the association between PGx variants and clinical response to risperidone in children with ASD, in a population highly representative of real-world risperidone use and efficacy. The methodology includes: (1) systematic assessment of therapeutic response using standardized psychometric protocols to measure objective changes before and after risperidone treatment; (2) genotyping using a broad pharmacogenomic panel with clinically relevant variants recognized by resources such as PharmGKB and CPIC; and (3) epigenetic analysis to explore potential regulatory effects of variants associated with therapeutic outcomes. The expected results will contribute to building the evidence base required for implementing pharmacogenomics in ASD clinical practice, particularly in underrepresented populations such as the Brazilian one. (AU)