Linkage study of the alpha 2A adrenergic receptor in attention-deficit hyperactivity disorder families

Attention-deficit hyperactivity disorder (ADHD) is a common childhood psych iatric disorder, characterized by marked and pervasive inattention, hyperac tivity, and impulsiveness. An alteration in the expression or function of t he adrenergic system has been suggested to be involved in ADHD based on ani mal models, pharmacological interventions, and the neural circuitry of atte ntional processes. The efficacy of clonidine in reducing disruptive behavio rs in some children with ADHD argues for a causal role of the adrenergic sy stem and more specifically for the alpha 2A receptors as clonidine is an al pha 2A agonist that inhibits release of noradrenaline into the synapse. In animal studies, alpha 2A receptor agonists have also been shown to improve performance on working memory tasks under distracting conditions, indicatin g that these receptors function in the regulation of attention. We examined the possibility that the gene for the alpha 2A adrenergic receptor (ADRA2A ) is linked to ADHD by testing a polymorphism located in the promoter regio n of the ADRA2A gene in a sample of 94 nuclear families with an ADHD proban d, We found no evidence for linkage of the ADRA2A gene with ADHD, using the trans- mission disequilibrium test in this set of families. (C) 2001 Wiley -Liss, Inc.