Attention deficit hyperactivity disorder (ADD ADHD) is a brain disorder that may have a number of different causes. Studies of families suggest that genetic factors contribute to ADHD. It seems to "run in families", at least in some families.

When a child is diagnosed with ADHD, there is a strong possibility that it will be found in other blood relatives, too. For example, studies have shown that one-third of all men who had ADHD in their youth have biological children with ADHD.

A number of studies are now taking place in the U.S. and Europe to try to find genes that lead to susceptibility to ADHD.

Our team has two such studies that are fairly typical of how a genetic study is run. The first study has involved getting clinical information and DNA from 18 very large, extended families in Colombia, South America. With our Colombian colleagues and Dr. F. Xavier Castellanos of New York University, we are in the process of studying the DNA from over 400 individuals from these families.

A second study is also going on here in the United States. For this study, we are recruiting families who have at least two children; at least one of the children in the family has to have ADD or ADHD. We try to enroll whole families: mother, father, and all the children, even those that do not have a diagnosis of ADD or ADHD.

Decoding the DNA of ADHD

Research in the area of the genetic susceptibility to ADHD is active. Two groups for example, one in California and one in the Netherlands have found suggestive evidence for linkage on several human chromosomes. Linkage is the inheritance of two or more genes in the same region on a chromosome. A chromosome is a structure in the nucleus of a cell that carried genetic information.

We say that a gene, a section of DNA that contains "instructions" for forming a functional "product"(ADHD for example) is "linked" to another marker gene on a chromosome; if they are so close together that they almost always are inherited together. Our own unpublished data suggest that two of the same regions the California and Dutch groups found are proving of interest to us.

The key, however, is to study more families, since the ability to detect linkage increases with more families. With the study of more small and large families with ADHD our research team at the National Institutes of Health in Bethesda, Maryland and our colleagues in California and the Netherlands will be able to find the genetic causes for ADHD. In the future this knowledge may help to specifically tailor therapies for a child or an adult with ADHD based on the underlying cause.

ADHD in the Family Tree?

Families who are interested in joining our study call, email or write to us. They give us their consent to be interviewed by a nurse or social worker on our study team. They also agree that each family member will give a few teaspoons of blood (drawn by their doctor or local lab) for us to use in genetic studies.

The interviewer spends about one hour on the phone with one of the parents asking them questions about the family medical and mental health history. The interviewer uses the information to construct a phenotype for each family member. A phenotype for this study means whether or not an individual has ADHD.

The interviewer also draws a pedigree or family tree showing each member of the family and how they are related to each other. All the information collected about a family is stored in locked files so that no one outside the research team can look at it.

Once we have phenotype information about a family and a tube of blood from each family member, we extract the DNA from the blood. DNA is the chemical code for genes. Although everyone, except for identical twins, has a unique combination of genes or genotype, brothers and sisters share DNA from their parents. We are looking for a DNA pattern that is the same in people with ADHD and different in those who do not have ADHD.

Our work has been made a little easier now that the Human Genome Project has sequenced our genetic code. But we still have a lot of work to do. The discovery of genes that contribute to ADHD could help make the diagnosis easier. It might also make it possible to find better treatments for people with ADHD.

To learn more about participating in the ADHD and Genetics Study, visit www.genome.gov, e-mail prpl@cc.nih.gov or call 1-800-411-1222 (TTY #1-866-411-1010). Information is available in English and Spanish. For more information about genetics, visit genome.gov/Education or contact the NHGRI Communications Office 301-402-0911 or e-mail spencerg@mail.nih.gov .

References

• Ogdie MN, Macphie IL, Minassian SL, Yang M, Fisher SE, Francks C, Cantor RM, McCracken JT, McGough JJ, Nelson SF, Monaco AP, Smalley SL. A genome-wide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. Am J Hum Genet. 2003 May;72(5):1268-79.
• Bakker SC, van der Meulen EM, Buitelaar JK, Sandkuijl LA, Pauls DL, Monsuur AJ, van 't Slot R, Minderaa RB, Gunning WB, Pearson PL, Sinke RJ. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q. Am J Hum Genet. 2003 May;72(5):1251-60.