Association between dopamine transporter (DAT1) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder.
A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 3' variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index (leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale (no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.
Bellgrove
Mark A
MA
Department of Psychology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. bema@unimelb.edu.au
Hawi
Ziarih
Z
Kirley
Aiveen
A
Fitzgerald
Michael
M
Gill
Michael
M
Robertson
Ian H
IH
D000293:Adolescent; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate; D004298:Dopamine