Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention-deficit/hyperactivity disorder?

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex childhood-onset psychiatric disorder characterized by marked symptoms of inattention, hyperactivity, and impulsivity. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Although most of the molecular studies have investigated the dopamine D4 receptor gene (DRD4) and the dopamine transporter gene (DAT1) genes in its etiology, pharmacological and brain imaging evidences seem to indicate that genes of the adrenergic system could also be attractive for association studies. We investigated a sample of 96 Brazilian ADHD children and adolescents and their parents for the ADRA2A MspI polymorphism. Although no association with either MspI allele was observed through the haplotype relative risk (HRR) analysis, effects of the ADRA2A gene on inattention and combined (inattention + hyperactivity/impulsivity) symptom scores were detected (U = 222.5, z = 2.19, P = 0.03; and U = 208.5, z = 2.32, P = 0.02, respectively). Our results suggest that the ADRA2A gene might have a small effect on ADHD susceptibility or that this gene might modulate the severity of the disorder. They are also consistent with the noradrenergic theories of ADHD, suggesting a role for the alpha2A adrenergic receptors in the disorder.