Journal Article

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

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

2023

Overview

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. After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis. 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. 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. •There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: ADHD / Age / Aging / Attention Deficit Disorder with Hyperactivity - genetics / Attention Deficit Disorder with Hyperactivity - metabolism / Attention deficit hyperactivity disorder / Biomarkers / Biomarkers - metabolism / Bisulfite / Blood / Cancer / Child / Children / DNA methylation / DNA Methylation - genetics / DNAmAge / Energy metabolism / Epi-signature / Epigenesis, Genetic / Epigenetic / Epigenetics / Etiology / Gene expression / Genes / Genetic testing / Heritability / Humans / Hyperactivity / Kruskal-Wallis test / Mental disorders / Metabolism / Methylation / Nervous system / Neurology / Neurosurgery / Ontology / Oxidative metabolism / Oxidative stress