Genes and attention-deficit hyperactivity disorder

In a collaborative research program on attention-deficit hyperactivity disorder (ADHD) initiated 20 years ago at UC Irvine. we adopted Cantwell's (1994) approach to define a refined phenotype for use in studies of the biological bases of this disorder. We have used this refined phenotype (ADHD-Combined Type without internalizing comorbidities) in our molecular genetic studies of ADHD. which have paralleled the emerging literature in this new field. In our research program. we used the candidate gene approach, with hypotheses derived from the dopamine theory of ADHD and Posner and Raichle's (1994) theory or attention. We proposed a candidate dopamine gene (DRD4) and discovered an association with ADHD due to an increase prevalence of the '7-repeat' allele defined by a 48-base-pair variable number of tandem repeats in exon III. The DRD4-ADHD association has now been confirmed by multiple groups around the world. In the next steps of our research program, we are evaluating the impact of a putative DRD4 risk allele on cognition, initiating an investigation of DNA sequence variation in DRD4 alleles, and investigating the association of ADHD with other candidate genes. Using our collaborative research program as an example, we will review the history and Current status of molecular genetic studies of ADHD. (C) 2001 Association for Research in Nervous and Mental Disease. Published by Elsevier Science B.V. All rights reserved.