Dopamine genes and ADHD

Family, twin, and adoption studies have documented a strong genetic basis f or ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of spe cific genes that are functionally associated with ADHD/HKD, and dopamine ge nes have been the initial candidates based on the site of action of the sti mulants drugs, which for a half century have provided the primary pharmacol ogical treatment for ADHD/HKD, Two candidate dopamine genes have been inves tigated and reported to he associated with ADHD/HKD, the dopamine transport er (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993 998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine re ceptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996,1:121-124; Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998; 3.38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus De velopment Conference: Diagnosis and Treatment of Attention Deficit Hyperact ivity Disorder, November 1998. p. 37-42] have suggested that specific allel es of these dopamine genes may alter dopamine transmission in the neural ne tworks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 g ene may be associated with hyperactive re-uptake of dopamine or that the 7- repeat allele of the DRD4 gene may be associated with a subsensitive postsy naptic receptor). These and other variants of the dopamine hypothesis of AD HD will be discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.