Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Dopaminergic genotype biases spatial attention in healthy children

In everyday life, our sensory system is bombarded with visual input and we rely upon attention to select only those inputs that are relevant to behavioural goals. Typically, humans can shift their attention from one visual field to the other with little cost to perception. In cases of, unilateral neglect', however, there is a persistent bias of spatial attention towards the same side as the damaged cerebral hemisphere. We used a visual orienting task to examine the influence of functional polymorphisms of the dopamine transporter gene (DAT1) on individual differences in spatial attention in normally developing children. DAT1 genotype significantly influenced spatial bias. Healthy children who were homozygous for alleles that influence the expression of dopamine transporters in the brain displayed inattention for left-sided stimuli, whereas heterozygotes did not. Our data provide the first evidence in healthy individuals of a genetically mediated bias in spatial attention that is related to dopamine signalling.

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1-9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefromal cortex dysfunction in children with HFA. (c) 2007 Elsevier Ltd. All rights reserved.

Response variability in Attention Deficit Hyperactivity Disorder: Evidence for neuropsychological heterogeneity

Response time (RT) variability is a common finding in ADHD research. RT variability may reflect frontal cortex function and may be related to deficits in sustained attention. The existence of a sustained attention deficit in ADHD has been debated, largely because of inconsistent evidence of time-on-task effects. A fixed-sequence Sustained Attention to Response Task (SART) was given to 29 control, 39 unimpaired and 24 impaired-ADHD children (impairment defined by the number of commission errors). The response time data were analysed using the Fast Fourier Transform, to define the fast-frequency and slow-frequency contributions to overall response variability. The impaired-ADHD group progressively slowed in RT over the course of the 5.5 min task, as reflected in this group's greater slow-frequency variability. The fast-frequency trial-to-trial variability was also significantly greater, but did not differentially worsen over the course of the task. The higher error rates of the impaired-ADHD group did not become differentially greater over the length of the task. The progressive slowing in mean RT over the course of the task may relate to a deficit in arousal in the impaired-ADHD group. The consistently poor performance in fast-frequency variability and error rates may be due to difficulties in sustained attention that fluctuate on a trial-to-trial basis. (c) 2006 Elsevier Ltd. All rights reserved.

In vitro testing of chitosan in gentamicin-loaded bone cement No antimicrobial effect and reduced mechanical performance

Background and purpose Efforts to prevent infection of arthroplasties, including the use of antibiotic-loaded bone cement, are not always successful. We investigated whether the incorporation of chitosan in gentamicin-loaded bone cement increases antibiotic release, and prevents bacterial adherence and biofilm formation by clinical isolates of Staphylococcus spp. In addition, we performed mechanical and degradation tests.