Dopamine genes and ADHD.
Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (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 receptor 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 Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene 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 postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.
Swanson
J M
JM
Child Development Center, University of California at Irvine, 92715, USA. jmswanso@uci.edu
Flodman
P
P
Kennedy
J
J
Spence
M A
MA
Moyzis
R
R
Schuck
S
S
Murias
M
M
Moriarity
J
J
Barr
C
C
Smith
M
M
Posner
M
M
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D005006:Ethnicity; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010641:Phenotype; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D018570:Risk Assessment
D002352:Carrier Proteins; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D004298:Dopamine