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

Molecular Diagnosis & Therapy, vol. 26, pp. 581–606

Abstract

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.

Authors 2

1. Charlotte A. M. Cecil corresponding Aachen Molecular Epidemiology Department of Biomedical Data Sciences

   Erasmus MC · Leiden University Medical Center · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands. c.cecil@erasmusmc.nl

   Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. c.cecil@erasmusmc.nl

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. c.cecil@erasmusmc.nl

   Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands

   Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

2. Joel T. Nigg

   Oregon Health & Science University

   Affiliation as printed

   Division of Psychology, Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA