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17 September 2014
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The Genetic Investigation of ADHD and the IMAGE Project

By Dr Philip Asherson at the Institute of Psychiatry, Kings College London.

Horizon: Living with ADHD: Programme summary

International research has established that there is a strong genetically inherited contribution to attention deficit hyperactivity disorder (ADHD) and the genetic mechanisms involved are being sought with considerable success. It is now established that variants of several genes occur more frequently in children with ADHD than in other children.

None of these genes are necessary or sufficient on their own to cause ADHD. Rather it is the cumulative effects of several genes alongside interaction with the environment that is thought to bring about ADHD. A major challenge for scientists now is to find out how the genetic risks are translated into disorder and to use research findings to improve the lives of individuals with ADHD.

Family studies
ADHD is a common disorder affecting around 1 in 30 children and 1 in 100 adults in the United Kingdom. Genetic research into ADHD started with the recognition by Morrison & Stewart and Cantwell in the early 1970s that hyperactivity aggregates in families. Recent studies found that the brothers or sisters of children with ADHD are far more likely to have ADHD themselves, with a chance of around 1 in 5.

This suggests that genes are likely to be important in ADHD, although increase risk to family members may also be due to shared experiences or exposure to environmental toxins. The findings from twin studies have however confirmed that genes are indeed a major influence on ADHD, since genetically identical twins are far more likely to both have ADHD than non-identical twins.

Progress in molecular genetics
The response of ADHD symptoms to stimulants such as methylphenidate led scientists to focus on genes involved in brain systems affected by these drugs; particularly the dopamine system. Dopamine is a naturally occurring brain chemical that acts as a signal between brain cells. Genetic studies have found that variation in genes that regulate the dopamine signal increase risk for ADHD.

The genes involved are the dopamine transporter gene (which stimulants act directly on), the dopamine D4 and D5 receptors and SNAP-25, a gene that controls the way dopamine is released in the brain. Further research will look at many other genes that regulate this system as well as genes involved in the way that the human brain develops and responds to the environment.

We are now entering an exciting phase in ADHD genetic research when we will start the search for new genes. Already groups in Holland, the United States and Columbia have identified regions of the human genome (the entire set of human chromosomes) that may contain genes that influence ADHD.

Searching for genes is rather like looking for a small needle in a very large haystack. Since sequencing the human genome was completed in the year 2000, very high-density genetic maps that enable us to map all human genes are being created at an incredible rate. For example, whereas in the past we could only measure a few genetic markers at a time, the most recent technology allows us to simultaneously measure around 500,000 markers.

Scientists can take full advantage of what is being called the New Genomics. This has the potential to discover new genes that effect ADHD, genes that we cannot even imagine at this time. The discovery of such genes may open up entirely new ways of thinking about ADHD with exciting new possibilities for improving the health of individuals with ADHD.

The International Multi-centre ADHD Gene project (The IMAGE project)
The National Institute of Health in the United States wanted to help scientists learn about how genes affect the development of ADHD. With this in mind, they funded the IMAGE project to gather medical information and DNA from individuals with ADHD, as well as from their brothers, sisters and parents.

The idea of this project is to create a resource that can be used both now and in the future to find the genes that cause ADHD. This is an exciting opportunity since the resource will be available to some of the best scientists in the world who wish to find the genes involved and identify the ways that our genes (nature) interact with our environment (nurture). Groups from Belgium, Germany, Holland, Ireland, Israel, Spain, Switzerland, the United Kingdom and the United States are involved in this project. IMAGE research teams have now seen over 800 families and we aim to recruit a further 600 families.

Taking part in the IMAGE project
If you wish to consider taking part in the IMAGE project and want to find out more, our research team in London will be very happy to discuss the project with you and answer any of your questions. The project would not be possible without the help and commitment from all the families that have taken part in the study.

Who can take part in the IMAGE project?
We are looking for families with one or more children who have ADHD and are currently attending school in the United Kingdom. To take part in the study your family must consist of at least two children, one of who has been diagnosed with ADHD. We will be looking for genes that are shared by siblings who both have ADHD and genes that are not shared by siblings where one has ADHD and the other does not.

Contact Details
Address: The IMAGE Project, The SGDP Centre, Memory Lane, Institute of Psychiatry P080, De Crespigny Park, London, SE5 8AF
Freephone: 0800 092 3392

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 Elsewhere on the web

ADHD support group.

The National Attention Deficit Disorder Information and Support Service.

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Identifying the genes involved in ADHD and related behavioural traits.

Royal College of Psychiatrists: ADHD information
Factsheet for parents, teachers and young people.

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