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Genetic risk factors and gene–environment interactions in adult and childhood attention-deficit/hyperactivity disorder

Palladino, Viola S.; McNeill, Rhiannon; Reif, Andreas; Kittel-Schneider, Sarah

doi: 10.1097/YPG.0000000000000220
Review Article

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder. In recent years, genetic studies have revealed several risk gene variants associated with ADHD; however, these variants could only be partly replicated and are responsible for only a fraction of the whole heritability of ADHD estimated from family and twin studies. One factor that could potentially explain the ‘missing heritability’ of ADHD is that childhood and adult or persistent ADHD could be genetically distinct subtypes, which therefore need to be analyzed separately. Another approach to identify this missing heritability could be combining the investigation of both common and rare gene risk variants as well as polygenic risk scores. Finally, environmental factors are also thought to play an important role in the etiology of ADHD, acting either independently of the genetic background or more likely in gene–environment interactions. Environmental factors might additionally convey their influence by epigenetic mechanisms, which are relatively underexplored in ADHD. The aforementioned mechanisms might also influence the response of patients with ADHD to stimulant and other ADHD medication. We conducted a selective review with a focus on risk genes of childhood and adult ADHD, gene–environment interactions, and pharmacogenetics studies on medication response in childhood and adult ADHD.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany

Received 17 November 2018 Revised14 January 2019

Accepted 20 January 2019

Correspondence to Sarah Kittel-Schneider, MD, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Heinrich-Hoffmann Street 10, 60528 Frankfurt, Germany, Tel: +49 696 301 5347; fax: +49 696 301 5290; e-mail:

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