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Abstract: The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials. [Copyright &y& Elsevier]

Abstract: Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to dopamine signaling is suggested in ADHD that may be ameliorated by methylphenidate (MPH). This study investigated the effects of MPH administration on the variability in RT and error performance on a sustained attention task of a group of 31 medication naïve children with ADHD, compared with 22 non-ADHD, non-medicated, control children. All children performed the fixed-sequence sustained attention to response task (SART) at two time-points: at baseline and after six weeks. The children with ADHD were tested when medication naive at baseline and after six weeks of treatment with MPH and whilst on medication. The medication naïve children with ADHD performed the SART with greater errors of commission and omission when compared with the control group. They demonstrated greater standard deviation of RT and fast moment-to-moment variability. They did not differ significantly from the control group in terms of slow variability in RT. MPH administration resulted in reduced and normalised levels of commission errors and fast, moment-to-moment variability in RT. MPH did not affect the rate of omission errors, standard deviation of RT or slow frequency variability in RT. MPH administration may have a specific effect on those performance components that reflect sustained attention and top–down control rather than arousal. [Copyright &y& Elsevier]

Abstract: ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment. Neuropsychological heterogeneity may, in part, reflect underlying genetic differences. Here we examined sustained attention, response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD (n =22) in relation to dopamine transporter genotype (DAT1) and also controls (n =20). Participants performed the sustained attention to response task (SART) (testing sustained attention and response variability) and the greyscales task (a perceptual measure of attentional bias). The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects. The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance. The ADHD group was sub-divided into those individuals with two copies of the “high-risk” 10-repeat allele (high-risk DAT1) versus those with one or no copies of this allele (low-risk DAT1). The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls, whereas the latter two groups did not differ. Further, the high-risk DAT1 group showed an attenuated spatial asymmetry, relative to the low-risk DAT1 ADHD group, who showed the typical leftward attentional asymmetry. Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD. The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD. [Copyright &y& Elsevier]