Dopaminergic Haplotype as a Predictor of Spatial Inattention in Children With Attention-Deficit/Hyperactivity Disorder

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.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.A case-control design was used.Children with ADHD were recruited from clinics or support groups in Ireland. Typically developing children were recruited from schools in and around Dublin, Ireland.One hundred fifteen children were recruited (ADHD = 50, control = 65). Groups were matched for age but differed in estimated intelligence.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.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.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.Heterogeneity in selective attention in ADHD can be explained by a replicated genetic risk factor for ADHD, the 10/3 DAT1 haplotype

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided

An overview of the pharmacogenetics and molecular genetics of ADHD

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, symptoms of which include inattentiveness, impulsiveness, distractibility and hyperactivity. Although the etiology of ADHD is not known, high heritability estimates (ranging from 60-90%) have been reported. The mode of inheritance is also unknown, however, it is widely believed that multiple susceptibility genes (each of small effect) are contributing to the liability of the disorder. Animal, pharmacological and molecular studies have implicated disruption in catecholamine neurotransmission (dopaminergic, serotonergic, and noradrenergic) in the etiology of ADHD. Recent genetic studies have identified ADHD susceptibility genes including DAT1, DRD4 and DRD5. In addition, there is evidence that DNA variation at the serotonin transporter (5-HTT), serotonin receptor 1B (5-HT1B) and the synaptosomal associated protein-25 (SNAP-25) genes contribute to susceptibility for ADHD. Genetic variants at these and other candidate genes have been examined for their potential to predict medication response in ADHD. Preliminary results are conflicting with no clear pattern emerging. However, the numbers of pharmacogenetic studies to date are limited and are mainly focused on methylphenidate and variants at the dopaminergic system genes. A more focused approach is required, examining genetic variation in genes involved kinetically and dynamically in medications used to treat ADHD. In this context, studies should be extended to include atomoxetine, a selective inhibitor of the noradrenergic transporter used in the treatment of ADHD. These studies might include a range a noradrenergic system genes

fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD

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 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

Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene

Objective: A naturalistic, prospective study of the influence of genetic variation on dose prescribed, clinical response, and side effects related to stimulant medication in 77 children with attention-deficit/hyperactivity disorder (ADHD) was undertaken. The influence of genetic variation of the CES1 gene coding for carboxylesterase 1A1 (CES1A1), the major enzyme responsible for the first-pass, stereoselective metabolism of methylphenidate, was investigated. Methods: Parent- and teacher-rated behavioral questionnaires were collected at baseline when the children were medication naive, and again at 6 weeks while they were on medication. Medication dose, prescribed at the discretion of the treating clinician, and side effects, were recorded at week 6. Blood and saliva samples were collected for genotyping. Single nucleotide polymorphisms (SNPs) were selected in the coding, non-coding and the 3 flanking region of the CES1 gene. Genetic association between CES1 variants and ADHD was investigated in an expanded sample of 265 Irish ADHD families. Analyses were conducted using analysis of covariance (ANCOVA) and logistic regression models. Results: None of the CES1 gene variants were associated with the dose of methylphenidate provided or the clinical response recorded at the 6 week time point. An association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate was found. The two associated CES1 markers were in linkage disequilibrium and were significantly associated with ADHD in a larger sample of ADHD trios. The associated CES1 markers were also in linkage disequilibrium with two SNP markers of the noradrenaline transporter gene (SLC6A2). Conclusions: This study found an association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate. These markers were in linkage disequilibrium together and with two SNP markers of the noradrenaline transporter gene

Defining entertainment: an approach

Entertainment is a key cultural category. Yet the definition of entertainment can differ depending upon whom one asks. This article maps out understandings of entertainment in three key areas. Within industrial discourses, entertainment is defined by a commercial business model. Within evaluative discourses used by consumers and critics, it is understood through an aesthetic system that privileges emotional engagement, story, speed and vulgarity. Within academia, entertainment has not been a key organizing concept within the humanities, despite the fact that it is one of the central categories used by producers and consumers of culture. It has been important within psychology, where entertainment is understood in a solipsistic sense as being anything that an individual finds entertaining. Synthesizing these approaches, the authors propose a cross-sectoral definition of entertainment as ‘audience-centred commercial culture’