Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential.

Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating neurodevelopmental disorder influenced by both genetic and environmental factors, typically identified in the school-age years but hypothesized to have developmental origins beginning in utero. To improve current strategies for prediction, prevention and treatment, a central challenge is to delineate how, at a molecular level, genetic and environmental influences jointly shape ADHD risk, phenotypic presentation, and developmental course. Epigenetic processes that regulate gene expression, such as DNA methylation, have emerged as a promising molecular system in the search for both biomarkers and mechanisms to address this challenge. In this Current Opinion, we discuss the relevance of epigenetics (specifically DNA methylation) for ADHD research and clinical practice, starting with the current state of knowledge, what challenges we have yet to overcome, and what the future may hold in terms of methylation-based applications for personalized medicine in ADHD. We conclude that the field of epigenetics and ADHD is promising but is still in its infancy, and the potential for transformative translational applications remains a distant goal. Nevertheless, rapid methodological advances, together with the rise of collaborative science and increased availability of high-quality, longitudinal data make this a thriving research area that in future may contribute to the development of new tools for improved prediction, management, and treatment of ADHD.