Another strong candidate gene for ADHD, based on pharmacological data analysis of animal models and association studies, is the gene encoding Brain-Derived Neurotrophic Factor (BDNF). Studies investigating association of a genetic variant in this gene in children with ADHD and controls have, however, shown controversial results. In a high-powered association study in 1445 adult ADHD patients and 2247 controls from IMpACT no association between this genetic variant and adult ADHD was found. This confirms that the BDNF variant is not a risk factor for adult ADHD (Ribases et al., presented at the ECNP Congress 2009).

So far, risk genes for ADHD have primarily been derived from animal models and pharmacological studies. Recently, it has become possible to search for such genes on a genome-wide basis, without prior hypotheses about specific candidate pathways. This approach has delivered a first gene for ADHD in children, CDH13, encoding a cell-adhesion gene with a role in early brain development (Lasky-Su et al., 2008; Lesch et al., 2008). A preliminary analysis in IMpACT suggests that this gene also plays a role in the adult form of the disorder (presentation at the ECNP Congress 2009).

Additional genetic analyses, both from earlier candidate-gene research in children and from genome-wide association studies, are currently ongoing within IMpACT. With the adult form of ADHD being the most severe one, the findings of the IMpACT project, focusing on the genetics of ADHD in adults in the largest clinical ADHD sample worldwide, can be expected to guide future research in this challenging field.

Clinical implications 

The genetic mechanisms involved in ADHD are being studied with considerable success by several centres worldwide. The International Multicenter persistent ADHD CollaboraTion, IMpACT, with its large sample of adult patients with ADHD, has become an important tool for the (re-)investigation of the role of previously suggested genetic risk factors for ADHD, and the mechanisms leading from gene to disease. The large IMpACT sample will facilitate the identification of new genes for ADHD. For this reason, a genome-wide search for new risk genes should be carried out in this sample. The findings of IMpACT will help to identify targets for the development of new and more effective treatments for ADHD. In addition, these findings may contribute to the prediction of persistence of the disorder already in children, supporting disease prevention.

Conclusion

Attention deficit/hyperactivity disorder (ADHD) is not merely a child-psychiatric disorder that persists into young adulthood, but an important and unique manifestation of psychopathology across the lifespan (Kooij et al., 2005).

The majority of patients affected by ADHD in childhood carry ADHD symptoms, or even the full ADHD-diagnosis, into adulthood. Since adult ADHD is associated with social and professional problems and, consequently, considerable costs, efforts are needed to increase the detection and treatment of adult ADHD.

The recent expansion of knowledge in genetics, brain imaging, and behavioural research is leading to a better understanding of the causes of ADHD, and paving the way for strategies for the development of more effective treatments for all age groups affected by this disorder and the prevention of the progression of disease into adulthood.

Major breakthroughs are expected from the currently ongoing International Multicenter persistent ADHD CollaboraTion (IMpACT), which is investigating the largest clinical ADHD sample worldwide.

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