Analysis of DNA methylation patterns in Brazilian patients with Alcohol and Cocaine Use Disorder

• Grant number: 25/22713-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2026
• End date: December 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Isabel Cristina Céspedes
• Grantee: Letícia dos Santos Doracio Gonçalves
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Introduction: Substance Use Disorder (SUD) is characterized by chronic and progressive substance use, triggering physiological, cognitive, and behavioral impairments. Patients commonly present a polydrug profile with concomitant use of alcohol and cocaine (ACD). Exposure to these substances induces epigenetic modulations, most notably DNA methylation, leading to structural and functional dysregulation of nervous tissue, impacting synaptic neuroplasticity, neurotransmission, and neuroinflammation. Furthermore, the impact of substances on different tissues can accelerate the development of age-related diseases, contributing to increased morbidity and mortality. Objective: To analyze the DNA methylation pattern and epigenetic aging resulting from chronic and concomitant alcohol and cocaine use in Brazilian patients diagnosed with ACD. Methods: Using information from a database, 57 patients diagnosed with ACD and 70 healthy control patients will be analyzed. Socioeconomic data (age, education, marital status, ethnicity), Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) scores, and epigenetic data will be considered. Raw epigenetic data were obtained using the Infinium Methylation EPIC BeadChip 2.0 (Illumina, San Diego, CA, USA). Preprocessing for quality control will be performed initially, followed by the calculation of Differentially Methylated Loci (DMLs) and Differentially Methylated Regions (DMRs) (Meffil and SeSAMe packages). Finally, a pathway enrichment analysis will be performed. Epigenetic aging will be estimated (PhenoAge and GrimAge clocks) by comparing biological and chronological age. All analyses will be performed using RStudio. Expected results: We expect to identify differential DNA methylation patterns in patients with TAC compared to healthy controls, as well as evidence of accelerated epigenetic aging in these individuals. (AU)