Dopaminergic haplotype as a predictor of spatial inattention in children with attention-deficit/hyperactivity disorder.
BACKGROUND
A distinct pattern of selective attention deficits in attention-deficit/hyperactivity disorder (ADHD) has been difficult to identify. Heterogeneity may reflect differences in underlying genetics.


OBJECTIVE
To document an objective deficit of selective attention in a large sample of children with and without ADHD using spatial orienting paradigms. By stratifying samples according to the gene dosage of a risk haplotype of the dopamine transporter gene (DAT1), we could determine whether genetic factors predict spatial inattention in ADHD.


METHODS
A case-control design was used.


METHODS
Children with ADHD were recruited from clinics or support groups in Ireland. Typically developing children were recruited from schools in and around Dublin, Ireland.


METHODS
One hundred fifteen children were recruited (ADHD = 50, control = 65). Groups were matched for age but differed in estimated intelligence.


METHODS
Two versions of a visual spatial orienting task in which attention was directed by valid, neutral, or invalid cues to target locations. Sudden-onset peripheral cues (exogenous) and centrally presented predictive cues (endogenous) were used.


METHODS
To isolate an attention deficit in ADHD, groups were first compared using analysis of variance on the spatial orienting tasks. Multiple regression was used to assess the main effect of DAT1 haplotype status (heterozygous vs homozygous) and the interaction of diagnosis and genotype on those variables that discriminated children with and without ADHD.


RESULTS
Children with ADHD displayed deficits in reorienting attention from invalidly cued spatial locations, particularly for targets in the left visual field. DAT1 haplotype status predicted spatial reorienting deficits for left visual field targets (P = .007) but there was also a significant interaction of diagnosis and genotype (P = .02), which revealed the greatest impairment in children with ADHD homozygous for the DAT1 haplotype.


CONCLUSIONS
Heterogeneity in selective attention in ADHD can be explained by a replicated genetic risk factor for ADHD, the 10/3 DAT1 haplotype.
Bellgrove
Mark A
MA
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia 4072. m.bellgrove@uq.edu.au
Johnson
Katherine A
KA
Barry
Edwina
E
Mulligan
Aisling
A
Hawi
Ziarah
Z
Gill
Michael
M
Robertson
Ian
I
Chambers
Christopher D
CD
D000293:Adolescent; D001288:Attention / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D003463:Cues; D004298:Dopamine / Q000235:genetics* / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007494:Ireland; D008297:Male; D008957:Models, Genetic; D009949:Orientation / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D012307:Risk Factors; D013028:Space Perception / Q000502:physiology*
D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine