Duration discrimination in the range of milliseconds and seconds in children with ADHD and their unaffected siblings

Background Detecting genetic factors involved in attention deficit hyperactivity disorder (ADHD) is complicated because of their small effect sizes and complex interactions. The endophenotype approach eases this by coming closer to the relevant genes. Different aspects of temporal information processing are known to be affected in ADHD. Thus, some of these aspects could represent candidate endophenotypes for ADHD. Method Fifty-four sib-pairs with at least one child with ADHD and 40 control children aged 6-18 years were recruited and asked to perform two duration discrimination tasks, one with a base duration of 50 ms on automatic timing and one with a base duration of 1000 ms on cognitively controlled timing. Results Whereas children with ADHD, but not their unaffected siblings, were impaired in discrimination of longer intervals, both groups were impaired in discriminating brief intervals. Furthermore, a significant within-family correlation was found for discrimination of brief intervals. Task performances of subjects of the control group correlated with individual levels of hyperactivity/impulsivity for discrimination of brief intervals, but not of longer intervals. Conclusions Cognitively controlled and also automatic processes of temporal information processing are impaired in children with ADHD. Discrimination of longer intervals appears as a typical ‘disease marker' whereas discrimination of brief intervals shows up as a ‘vulnerability marker'. Discrimination of brief intervals was found to be familial and linked to levels of hyperactivity/impulsivity. Taken together, discrimination of brief intervals represents a candidate endophenotype of ADH

Reaction time performance in ADHD: Improvement under fast-incentive condition and familial effects

Background. Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD. Method. A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT task with baseline and fast-incentive conditions. Results. ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60-70%. Conclusions. The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADHD. © 2007 Cambridge University Press.published_or_final_versio

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ

Background Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. Method Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). Results Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. Conclusions The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADH

No association between two polymorphisms of the serotonin transporter gene and combined type attention deficit hyperactivity disorder

Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the sample of ADHD cases. © 2008 Wiley-Liss, Inc

Color perception deficits in co-existing attention-deficit/hyperactivity disorder and chronic tic disorders

Preliminary findings suggest that color perception, particularly of blue-yellow stimuli, is impaired in attention-deficit/hyperactivity disorder (ADHD) as well as in chronic tic disorders (CTD). However, these findings have been not replicated and it is unclear what these deficits mean for the comorbidity of ADHD + CTD. Four groups (ADHD, CTD, ADHD + CTD, controls) of children with similar age, IQ and gender distribution were investigated with the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Color-Word Task using a factorial design. Color perception deficits, as indexed by the FMT, were found for both main factors (ADHD and CTD), but there were no interaction effects. A preponderance of deficits on the blue-yellow compared to the red-green axis was detected for ADHD. In the Stroop task only the 'pure' ADHD group showed impairments in interference control and other parameters of Stroop performance. No significant correlations between any FMT parameter and color naming in the Stroop task were found. Basic color perception deficits in both ADHD and CTD could be found. Beyond that, it could be shown that these deficits are additive in the case of comorbidity (ADHD + CTD). Performance deficits on the Stroop task were present only in the 'pure' ADHD group. Hence, the latter may be compensated in the comorbid group by good prefrontal capabilities of CTD. The influence of color perception deficits on Stroop task performance might be negligible. © 2007 Springer-Verlag

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Familiality of neural preparation and response control in childhood attention deficit-hyperactivity disorder

Background Patients with attention deficit-hyperactivity disorder (ADHD) exhibit difficulties in multiple attentional functions. Although high heritability rates suggest a strong genetic impact, aetiological pathways from genes and environmental factors to the ADHD phenotype are not well understood. Tracking the time course of deviant task processing using event-related electrophysiological brain activity should characterize the impact of familiality on the sequence of cognitive functions from preparation to response control in ADHD. Method Preparation and response control were assessed using behavioural and electrophysiological parameters of two versions of a cued continuous performance test with varying attentional load in boys with ADHD combined type (n=97), their non-affected siblings (n=27) and control children without a family history of ADHD (n=43). Results Children with ADHD and non-affected siblings showed more variable performance and made more omission errors than controls. The preparatory Cue-P3 and contingent negative variation (CNV) following cues were reduced in both ADHD children and their non-affected siblings compared with controls. The NoGo-P3 was diminished in ADHD compared with controls whilst non-affected siblings were located intermediate but did not differ from both other groups. No clear familiality effects were found for the Go-P3. Better task performance was further associated with higher CNV and P3 amplitudes. Conclusions Impairments in performance and electrophysiological parameters reflecting preparatory processes and to some extend also for inhibitory response control, especially under high attentional load, appeared to be familially driven in ADHD and may thus constitute functionally relevant endophenotypes for the disorde

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

The High-Superior-Tension Technique: Evolution of Lipoabdominoplasty

Because abdominoplasty is associated with complications such as seroma and necrosis as well as epigastric bulging and a suprapubic scar located too high, the demand for this procedure is not as high as it otherwise might be. However, although these negative effects were common many years ago, their incidence has decreased dramatically with modern abdominoplastic techniques. One approach using a combination of abdominoplasty and liposuction or lipoabdominoplasty has resolved many of the problems faced with earlier techniques, offering aesthetically pleasing results and excellent reliability. The keys to successful lipoabdominoplasty, first developed as the high-superior-tension technique, are extensive liposuction, preservation of lymphatic trunks, preaponeurotic epigastric dissection, major muscle fascia plication, two high-tension paraumbilical sutures, hypogastric tension sutures, and closure of the dead spaces. The most recent updates to this technique are described in this article

Language, Truth, and Logic and the Anglophone reception of the Vienna Circle

A. J. Ayer’s Language, Truth, and Logic had been responsible for introducing the Vienna Circle’s ideas, developed within a Germanophone framework, to an Anglophone readership. Inevitably, this migration from one context to another resulted in the alteration of some of the concepts being transmitted. Such alterations have served to facilitate a number of false impressions of Logical Empiricism from which recent scholarship still tries to recover. In this paper, I will attempt to point to the ways in which LTL has helped to foster the various mistaken stereotypes about Logical Empiricism which were combined into the received view. I will begin by examining Ayer’s all too brief presentation of an Anglocentric lineage for his ideas. This lineage, as we shall see, simply omits the major 19th century Germanophone influences on the rise of analytic philosophy. The Germanophone ideas he presents are selectively introduced into an Anglophone context, and directed towards various concerns that arose within that context. I will focus on the differences between Carnap’s version of the overcoming of metaphysics, and Ayer’s reconfiguration into what he calls the elimination of metaphysics. Having discussed the above, I will very briefly outline the consequences that Ayer’s radicalisation of the Vienna Circle’s doctrines had on the subsequent Anglophone reception of Logical Empiricism