DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients

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Carvalho, Gleyson Francisco da Silva ; Costa, Thais Virginia Moura Machado ; Nascimento, Amom Mendes ; Wolff, Beatriz Martins ; Damasceno, Julian Gabriel ; Vieira, Lucas Liro ; Almeida, Vanessa Tavares ; de Oliveira, Yanca Gasparini ; de Mello, Claudia Berlim ; Muszkat, Mauro ; Kulikowski, Leslie Domenici

• Document type: Journal article
• Source: CLINICAL NEUROLOGY AND NEUROSURGERY; v. 228, p. 7-pg., 2023-04-11.

Abstract

Objective: Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD.Methods: After DNA extraction and bisulfite conversion, we performed methylation array experiment for dif-ferential methylation, ontological and biological age analysis.Results: The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD. Conclusion: Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers. (AU)

• FAPESP's process: 15/05350-5 - DNA methylation profile of peripheral blood in attention deficit hyperactivity disorder (ADHD) carriers by array
• Grantee: Thais Virginia Moura Machado Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/02565-8 - Methylation profile of disorder attention deficit hyperactivity disorder (ADHD) carriers by MLPA(Multiplex ligation-dependent probe amplification) and arrays
• Grantee: Leslie Domenici Kulikowski
• Support Opportunities: Regular Research Grants