Dopamine transporter 3'UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD

Sherif Karama,Valentin Mbekou,Anna Polotskaia,Edmund Sonuga-Barke,Johanne Bellingham,Sarojini Sengupta,Joseph Biederman,Natalie Grizenko,Ridha Joober,Marina Ter-Stepanian,Alysa Doyle,Rosherrie De Guzman

doi:10.1186/1471-244x-8-45

Abstract

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder.MethodsTo investigate the relationship between the dopamine transporter gene (SLC6A3) 3'-UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning.ResultsTaking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009) and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) Freedom From Distractibility Index (F = 7.125, p = 0.008), as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026) and WISC-III Digit Span performance (F = 6.28, p = 0.023). Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected.ConclusionResults are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD.

Highlights

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints
The present study examined executive function performance in children with ADHD in relation to the Variable Number of Tandem Repeats (VNTR) located in the 3' untranslated (UTR) region of the DAT1 gene in order to further characterize the association between genotype and behavior in children with ADHD
No significant differences between genotype groups were found in IQ, in diagnostic subtype of ADHD or in the number of ADHD items as assessed by the diagnostic interview schedule for children-parental report (DISC-IV)

Summary

Introduction

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder. Single photon emission computed tomography studies show high rates of striatal dopamine transporter activity in drug naive adults with ADHD [9,10,11]. A pooled odds ratio (OR) for ADHD from family studies for the dopamine transporter (DAT1) gene 10 repeat allele was found to be significant [6] and other meta-analyses have invariably shown positive ORs for this allele [12,13,14,15,16], not necessarily significant ones

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Discussion

Conclusion