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Dopamine genes and ADHD.

J M Swanson·P Flodman·J Kennedy·M A Spence·R Moyzis·S Schuck·M Murias·J Moriarity·C Barr·M Smith·M Posner
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Abstract

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.

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AllelesAttention Deficit Disorder with HyperactivityCarrier ProteinsDopamineDopamine Plasma Membrane Transport ProteinsEthnicityGene FrequencyHaplotypesHumansMembrane GlycoproteinsMembrane Transport ProteinsNerve Tissue ProteinsPhenotypeReceptors, Dopamine D2Receptors, Dopamine D4Risk AssessmentClinical TrialJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J M Swanson, P Flodman, J Kennedy, M A Spence, R Moyzis, S Schuck, M Murias, J Moriarity, C Barr, M Smith, M Posner. 2000. Dopamine genes and ADHD.. https://doi.org/10.1016/s0149-7634(99)00062-7

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