IMpACT, short for ‘International Multi-centre persistent ADHD CollaboraTion’, is a consortium of clinical and basic researchers from several European countries (The Netherlands, Germany, Spain, Norway, The United Kingdom, Sweden), from the United States of America and from Brazil. IMpACT currently coordinates biosamples and phenotypic information of over 4000 cases with persistent ADHD and over 8000 controls.

The mission of IMpACT is to perform and promote high quality research in ADHD across the lifespan. This research is aimed at identifying novel genetic variants for adult ADHD and at understanding the mechanisms underlying the effect of these genetic variants on disease risk. IMpACT members share data on their samples as well as biological material, which has resulted in the formation of the largest database for adult ADHD research, including information on over 4000 cases and more than 7000 controls.

IMpACT was formed in 2007 from members of the international ADHD Molecular Genetics Network (lead by Prof. Stephen V. Faraone) through an initiative of Prof. Barbara Franke, who has been leading the consortium since then. Senior and junior members of IMpACT meet at least twice a year for a dedicated IMpACT meeting. IMpACT members are dedicated to improve research on ADHD across the lifespan in general, but also are prepared to go out of their way to help each other perform research in the best possible manner. This sets our collaboration apart from many other professional consortia.

IMpACT’s first collaborative studies were based on meta-analyses of existing genotyping data for individual candidate genes for ADHD (see publication list). Through these approaches we found out that the gene for the dopamine transporter DAT1 has different risk alleles for childhood and adult ADHD. We also found out that several of the candidate genes for ADHD in children, like BDNF and DRD4, do not significantly increase the risk for the persistent form of ADHD. For the serotonin transporter encoding gene 5-HTT (or SERT), we could neither prove nor exclude a role in adult ADHD. This work has since been extended to include collaborative genotyping studies of new candidate genes, with new, genome-wide approaches (genome-wide association studies, exome chip analysis and exome sequencing) currently underway. In addition, using diverse approaches including bioinformatics, in vitro studies of proteins, cell culture models, in vivo research in animal models, we aim at mapping the pathways from gene of interest to disease.

The diagnosis of ADHD is still based on clinical interviews. So far, there are no biological markers available in order to diagnose ADHD by a biological test. The pharmacological treatment of ADHD focuses on the reduction of hyperactive, impulsive and/or inattentive symptoms, but does not approach the actual cause of the disorder and can therefore not contribute to a general recovery of the patients. Additionally, we still have insufficient knowledge about the actual causes of ADHD to develop treatment possibilities that could indeed tackle the underlying causes of this disorder. Consequently, research on these causal mechanisms of the development of ADHD is necessary. With a better understanding of these processes, we hopefully can correct aberrant neuronal processes in the brain with the use of new medication or other therapy options.

ADHD has a strong genetic heritability, as approximately 70-80% of the clinical symptoms of a patient can be ascribed to heritable factors. However, the heritability of ADHD is not based on one single genetic aberration in the genetic material of a patient, but in most of the patients multiple small genetic variations play a role at the same time. Each of these variations has a small effect on the disease risk of a person. The fact that in different ADHD patients different genetic variations play a role, makes the genetic basis of ADHD even more complex. Besides, these variations also occur in healthy individuals, although ADHD patients have (a lot) more of these genetic variations.

More insights into genes and genetic variants, that underlie ADHD, can improve our understanding of biological processes that differ in ADHD patients. Recently, we discovered that in ADHD the formation of connections between nerve cells during embryonic brain development progresses differently. However, the detection of genetic factors for ADHD is still a large puzzle. We think that there might be up to 1000 ADHD-related genes, and in each of these genes there are probably multiple genetic variations, which can increase the risk for ADHD. Until now, we only know very little of these genetic variants and not more than 10 different genes for ADHD have been described yet. For that reason, a lot more research is needed. Because the effects of individual genetic variants are so small, our research can only be conducted in large cohorts of ADHD patients and healthy people. Accordingly, the collaboration between several research groups, such as within the IMpACT group, is extremely important for the scientific progress.

IMpACT focuses its research on ADHD in adults, i.e. persistent ADHD. This is because it is the most severe form of ADHD. There is also evidence that genetic factors of persistent ADHD play a more prominent role than in childhood ADHD. Thus, the group of adult patients seems to be very helpful for our research on discovering the genetic factors underlying the development of this disorder.