Language and sociability: insights from Williams syndrome

One of the most compelling features of Williams syndrome (WS) is the widely reported excessive sociability, accompanied by a relative proficiency in expressive language, which stands in stark contrast with significant intellectual and nonverbal impairments. It has been proposed that the unique language skills observed in WS are implicated in the strong drive to interact and communicate with others, which has been widely documented in WS. Nevertheless, this proposition has yet to be empirically examined. The present study aimed at investigating the relationship between a brain index of language processing and judgments of approachability of faces, as a proxy for sociability, in individuals with WS as contrasted to typical controls. Results revealed a significant and substantial association between the two in the WS, but not in the control group, supporting the hitherto untested notion that language use in WS might be uniquely related to their excessive social drive

Facial emotion recognition in Williams syndrome and Down syndrome: A matching and developmental study

In this study both the matching and developmental trajectories approaches were used to clarify questions that remain open in the literature on facial emotion recognition in Williams syndrome (WS) and Down syndrome (DS). The matching approach showed that individuals with WS or DS exhibit neither proficiency for the expression of happiness nor specific impairments for negative emotions. Instead, they present the same pattern of emotion recognition as typically developing (TD) individuals. Thus, the better performance on the recognition of positive compared to negative emotions usually reported in WS and DS is not specific of these populations but seems to represent a typical pattern. Prior studies based on the matching approach suggested that the development of facial emotion recognition is delayed in WS and atypical in DS. Nevertheless, and even though performance levels were lower in DS than in WS, the developmental trajectories approach used in this study evidenced that not only individuals with DS but also those with WS present atypical development in facial emotion recognition. Unlike in the TD participants, where developmental changes were observed along with age, in the WS and DS groups, the development of facial emotion recognition was static. Both individuals with WS and those with DS reached an early maximum developmental level due to cognitive constraints

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Prevalence of Tuberculosis infection among teen-agers in Tuscany

Introduction. In Tuscany, Tuberculosis incidence is more thantriplicate from 1982 to the beginning of the third millennium.The impact of this trend on open population is not known, asupdated studies on Tuberculosis prevalence are not available.Tuberculin skin test provides the currently most widely used toolfor assessing Tuberculosis transmission in a community and theprevalence of infection as well.The objective of this investigation was the evaluation of tuberculin index by means of the Mantoux test in adolescents eighteen-years old.Results. The study was carried out in 21 secondary schools ofSiena and its Province; 1,138 students participated to this survey.The overall prevalence of subjects with a skin reaction size >5 mm was 1.6%; if the standard cut-off of 10 mm was used, the overall prevalence of a positive skin reaction was 0.4%. Riskfactors for a doubtful or positive reaction were previous immunization with BCG and migration from high-endemicity countries. Discussion. In Italy, studies on tuberculin index in young adultsare scanty and controversial: our results show a very low Tuberculosis prevalence and an epidemiological pattern typical ofcountries with low Tuberculosis endemicity.Conclusions. The slightly increase in Tuberculosis incidencehas no impact on the prevalence of latent Tuberculosis infection on our geographical area. We conclude that skin-test screening for Tuberculosis should be addressed to high risk population as migrants from Countries reporting high transmissionrate, those recently exposed to an infectious case and healthworkers

Electrophysiological study of local/global processing in Williams syndrome

Persons with Williams syndrome (WS) demonstrate pronounced deficits in visuo-spatial processing. The purpose of the current study was to examine the preferred level of perceptual analysis in young adults with WS (n = 21) and the role of attention in the processing of hierarchical stimuli. Navon-like letter stimuli were presented to adults with WS and age-matched typical controls in an oddball paradigm where local and global targets could appear with equal probability. Participants received no explicit instruction to direct their attention toward a particular stimulus level. Behavioral and event-related potential (ERP) data were recorded. Behavioral data indicated presence of a global precedence effect in persons with WS. However, their ERP responses revealed atypical brain mechanisms underlying attention to local information. During the early perceptual analysis, global targets resulted in reduced P1 and enhanced N150 responses in both participant groups. However, only the typical comparison group demonstrated a larger N150 to local targets. At the more advanced stages of cognitive processing, a larger P3b response to global and local targets was observed in the typical group but not in persons with WS, who instead demonstrated an enhanced P3a to global targets only. The results indicate that in a perceptual task, adults with WS may experience greater than typical global-to-local interference and not allocate sufficient attentional resources to local information

Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

A multimeasure approach to investigating affective appraisal of social information in Williams syndrome

People with Williams syndrome (WS) have been consistently described as showing heightened sociability, gregariousness, and interest in people, in conjunction with an uneven cognitive profile and mild to moderate intellectual or learning disability. To explore the mechanisms underlying this unusual social–behavioral phenotype, we investigated whether individuals with WS show an atypical appraisal style and autonomic responsiveness to emotionally laden images with social or nonsocial content. Adolescents and adults with WS were compared to chronological age-matched and nonverbal mental age-matched groups in their responses to positive and negative images with or without social content, using measures of self-selected viewing time (SSVT), autonomic arousal reflected in pupil dilation measures, and likeability ratings. The participants with WS looked significantly longer at the social images compared to images without social content and had reduced arousal to the negative social images compared to the control groups. In contrast to the comparison groups, the explicit ratings of likeability in the WS group did not correlate with their SSVT; instead, they reflected an appraisal style of more extreme ratings. This distinctive pattern of viewing interest, likeability ratings, and autonomic arousal to images with social content in the WS group suggests that their heightened social drive may be related to atypical functioning of reward-related brain systems reflected in SSVT and autonomic reactivity measures, but not in explicit ratings

Uncommon genetic syndromes and narrative production - Case Studies with Williams, Smith-Magenis and Prader- Willi Syndromes

This study compares narrative production among three syndromes with genetic microdeletions: Williams syndrome (WS), Smith-Magenis syndrome (SMS), and Prader-Willi syndrome (PWS), characterized by intellectual disabilities and relatively spared language abilities. Our objective is to study the quality of narrative production in the context of a common intellectual disability. To elicit a narrative production, the task Frog! Where Are You was used. Then, structure, process, and content of the narrative process were analysed in the three genetic disorders:WS (n52), SMS (n52), and PWS (n52). Data show evidence of an overall low narrative quality in these syndromes, despite a high variability within different measures of narrative production. Results support the hypothesis that narrative is a highly complex cognitive process and that, in a context of intellectual disability, there is no evidence of particular ‘hypernarrativity’ in these syndromes.This research was supported by the grants FEDER –

Enhanced prefrontal serotonin 5-HT1A currents in a mouse model of Williams-Beuren syndrome with low innate anxiety

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the hemizygous deletion of 28 genes on chromosome 7, including the general transcription factor GTF2IRD1. Mice either hemizygously (Gtf2ird1+/−) or homozygously (Gtf2ird1−/−) deleted for this transcription factor exhibit low innate anxiety, low aggression and increased social interaction, a phenotype that shares similarities to the high sociability and disinhibition seen in individuals with WBS. Here, we investigated the inhibitory effects of serotonin (5-HT) on the major output neurons of the prefrontal cortex in Gtf2ird1−/− mice and their wildtype (WT) siblings. Prefrontal 5-HT receptors are known to modulate anxiety-like behaviors, and the Gtf2ird1−/− mice have altered 5-HT metabolism in prefrontal cortex. Using whole cell recording from layer V neurons in acute brain slices of prefrontal cortex, we found that 5-HT elicited significantly larger inhibitory, outward currents in Gtf2ird1−/− mice than in WT controls. In both genotypes, these currents were resistant to action potential blockade with TTX and were suppressed by the selective 5-HT1A receptor antagonist WAY-100635, suggesting that they are mediated directly by 5-HT1A receptors on the recorded neurons. Control experiments suggest a degree of layer and receptor specificity in this enhancement since 5-HT1A receptor-mediated responses in layer II/III pyramidal neurons were unchanged as were responses mediated by two other inhibitory receptors in layer V pyramidal neurons. Furthermore, we demonstrate GTF2IRD1 protein expression by neurons in layer V of the prefrontal cortex. Our finding that 5-HT1A-mediated responses are selectively enhanced in layer V pyramidal neurons of Gtf2ird1−/− mice gives insight into the cellular mechanisms that underlie reduced innate anxiety and increased sociability in these mice, and may be relevant to the low social anxiety and disinhibition in patients with WBS and their sensitivity to serotonergic medicines

Executive function in Williams and Down syndromes

Williams (WS) and Down (DS) syndromes are characterised by roughly opposing ability profiles. Relative verbal strengths and visuospatial difficulties have been reported in those with WS, while expressive language difficulties have been observed in individuals with DS. Few investigations into the executive function (EF) skills of these groups have examined the effect of verbal/visuospatial task type on performance. Analogous verbal and visuospatial measures were administered to these populations within four EF domains: executive-loaded working memory (ELWM), inhibition, fluency and set-shifting. Performance in both groups was compared to that of typically developing (TD) children using regression techniques controlling for potentially influential cognitive/developmental factors. Individuals with WS showed the expected relative visuospatial difficulties, as indicated by poorer performance than TD individuals, on tests of ELWM and fluency. Individuals with DS displayed the expected relative verbal difficulty in the domain of set-shifting. In addition, each population showed pervasive deficits across modality in one domain; ELWM for individuals with DS, and inhibition for individuals with WS. Individuals with WS and DS showed EF difficulties in comparison to a TD group, but, their executive performance was affected by EF task type (verbal/visuospatial) and EF domain in different ways. While the findings indicated that EF in these populations is characterised by a range of specific strengths and weaknesses, it was also suggested that the relative verbal/visuospatial strengths associated with each population do not consistently manifest across EF domains. Lastly, syndrome specificity was indicated by the differences in groups’ performance patterns