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Abstract: Asymmetries of spatial attention are observed in both clinical and non-clinical populations. While lesions of the right hemisphere frequently result in symptoms of left neglect (right bias), the opposite pattern is often observed in healthy subjects, a phenomenon known as pseudoneglect. Pharmacological and animal studies have suggested a critical role for the catecholamines, in particular dopamine and noradrenaline, in modulating the direction and magnitude of spatial attentional bias. In the present study we investigated the effect of two catecholaminergic genes, DBH and DAT1, on performance in the Landmark task, a perceptual measure of spatial bias. 204 healthy participants performed the Landmark task and were genotyped for the DBH C-1021T and DAT1 3′UTR variants. Homozygosity for the DBH T allele, which is associated with relatively increased dopamine and decreased noradrenaline levels, resulted in a significant increase in rightwards spatial bias relative to the C allele. Similarly, homozygosity for the DAT1 9-repeat allele, which is associated with reduced dopamine transporter density, and consequently increased dopamine availability relative to the 10-repeat allele, was found to result in a greater degree of rightward bias. An additive effect of the two markers was also observed, such that the greatest degree of rightward spatial bias was observed in participants who possessed the ‘high dopamine’ alleles of both genes and the lowest degree in those without these alleles. These results provide the first evidence of genetic modulation of spatial bias in healthy adults. [ABSTRACT FROM AUTHOR]

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: 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]