ADHD is a heterogeneous disorder characterized by age-inappropriate inattention, motor activity, and/or impulse control. Its high prevalence in school-aged children (8 to 12%)  in combination with its significant negative impact on school and social adjustment as well as family wellbeing make it one of the most important public health problems in the child population. Multiple risk factors interact to increase liability to ADHD . While environmental risk factors such as pregnancy complications , family dysfunction  and drug abuse during pregnancy  have all been implicated in the etiology of ADHD, there is overwhelming evidence from twin studies that genes also contribute to the development of ADHD [2, 6, 7].
There has been a strong focus on the dopamine transporter in ADHD as psychostimulants, the first line medication for ADHD, have been shown to block this transporter as part of their mechanism of action . Further, single photon emission computed tomography studies show high rates of striatal dopamine transporter activity in drug naive adults with ADHD [9–11]. In keeping with this, a pooled odds ratio (OR) for ADHD from family studies for the dopamine transporter (DAT1) gene 10 repeat allele was found to be significant  and other meta-analyses have invariably shown positive ORs for this allele [12–16], although not necessarily significant ones.
While the above-mentioned genetic studies have examined allelic associations between specific polymorphisms and ADHD, genotypic approaches have also yielded support for DAT1 involvement. For instance, Loo et al. have reported that in patients with ADHD, there is an association between 10/10 DAT1 genotype and increased errors on a vigilance task when compared to a compound group composed of children having the 9/9 or 9/10 genotypes . Along similar lines, children with ADHD and carriers of both the 10/10 DAT1 genotype as well as a 7-repeat DRD4 allele have been reported as having a lower IQ than a combined group of carriers of other genotypes . Further, poor response to methylphenidate was associated, in ADHD children, with DAT1 10-repeat allele homozygosity in both prospective and naturalistic studies [19–21].
Due to the relatively small frequency of the 9/9 genotype in the general population and to the consequently small sample sizes generally acquired for this genotype, 10/10 genotype groups are usually compared to a combined group of subjects with the 9/9 and 9/10 genotypes (as well as other very rare genotypes). This being said, a few recent studies have compared genotypes separately. For instance, Cornish et al.  have shown, in normal boys, an association between the 10/10 repeat allele genotype and poorer mean scores on measures of selective attention and response inhibition compared to a group of 9/10 carriers. Joober et al. , using a 2-week prospective within subject crossover design have shown that children with ADHD and carriers of the 9/9 genotype displayed a significantly weaker response to methylphenidate than carries of the 9/10 genotype or carriers of the 10/10 genotype. Further, a recent study  demonstrated that individuals with ADHD and carriers of the 9/10 genotype tended to fair worse than carriers of the 10/10 genotype on a large set of variables including behavioral problems in childhood and adolescence, mother-teen relations at adolescence, and class rankings in high school. However, no significant differences between genotype groups were found in Wisconsin Card Sorting Test performance. The majority of findings in this study essentially supports the view that young carriers of the 9/10 genotype tend to fair worse than their 10/10 counterparts from a psychopathological perspective. While this work appears to contradict above-mentioned studies demonstrating a disadvantage for carriers of the 10/10 genotype, it is noteworthy that it's the first study, to the best of our knowledge, to separately look at DAT1 gene genotype in relation to behavior in children with ADHD.
Overall, these patterns of results are consistent with a high degree of heterogeneity in genetic effects and with the view that current candidate genes are only indirectly responsible for ADHD as they may instead be associated with specific clinical variants and/or behavioral dimensions of ADHD yet to be precisely identified. If this is the case, selecting candidate genes on the basis of their potential implication in modulating intermediate phenotypes (or endophenotypes) relevant to ADHD could improve the robustness of genetic results. While endophenotypes can exist at a number of levels, most studies to date have focused on the neuropsychological level. One such pathway with considerable empirical support implicates dysregulation of executive function processes (defined as the neurocognitive processes that maintain an appropriate problem-solving set to attain a future goal [25, 26]). Factor analyses of batteries of measures of executive function have revealed the four following factors: 1) response inhibition and execution, 2) working memory and updating, 3) set-shifting and task-switching, and 4) interference control [26–30]. Although most mental tasks involve almost every component of executive functioning to some degree, some tasks tap relatively highly into specific factors.
While traditionally, executive function tasks have been believed to rely mostly on the prefrontal cortex, the involvement of the basal ganglia is now being recognized [31, 32]. For instance, it has been shown that fronto-striatal pathway disconnection disrupts normal performance on classical cognitive frontal tasks in rats  and that the executive dysfunction frequently observed in Parkinson's disease is associated with altered pallidal-frontal processing . In keeping with this, one of the most replicated morphological alterations in brains of children with ADHD is small caudate and pallidum volumes .
Finding an association between executive function dysregulation and ADHD together with demonstration that dopamine neurotransmission is critical for normal executive functioning would highlight the plausibility of executive function as an endophenotype in ADHD. From a genetic standpoint, the DAT1 gene is known to be preferentially expressed in the basal ganglia and has been reported to influence caudate volume  and aspects of executive functioning in normal subjects . Furthermore and in keeping with the above, the dopamine transporter has been argued to play a critical role in regulating cortical signal-to-noise ratio during working memory via a cortico-striato-thalamo-cortical pathway . As reviewed by Doyle et al, family, twin, and adoption studies all suggest that EFs may index the familial/genetic liability to ADHD. Given the data discussed above, DAT1 gene is a compelling candidate gene to examine in relation to both EF performance and ADHD.
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. It is hypothesized that DAT1 gene genotype has an effect on executive function performance.