Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients

<p>Abstract</p> <p>Background</p> <p>Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder with hypothalamic dysfunction, early morbid obesity with hyperphagia, and specific psychiatric phenotypes including cognitive and behavioural problems, particularly disruptive behaviours and frequent temper outbursts that preclude socialization. A deficit in oxytocin (OT)-producing neurons of the hypothalamic paraventricular nucleus has been reported in these patients.</p> <p>Methods</p> <p>In a double-blind, randomised, placebo-controlled study, 24 adult patients with PWS received a single intranasal administration of 24 IU of OT or placebo and were tested 45 min later on social skills. Behaviours were carefully monitored and scored using an in-house grid as follows: over the two days before drug administration, on the half-day following administration, and over the subsequent two days. All patients were in a dedicated PWS centre with more than ten years of experience. Patients are regularly admitted to this controlled environment.</p> <p>Results</p> <p>Patients with PWS who received a single intranasal administration of OT displayed significantly increased trust in others (P = 0.02) and decreased sadness tendencies (P = 0.02) with less disruptive behaviour (P = 0.03) in the two days following administration than did patients who received placebo. In the half-day following administration, we observed a trend towards less conflict with others (p = 0.07) in the OT group compared with the placebo group. Scores in tests assessing social skills were not significantly different between the two groups.</p> <p>Conclusions</p> <p>This study needs to be reproduced and adapted. It nevertheless opens new perspectives for patients with PWS and perhaps other syndromes with behavioural disturbances and obesity.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01038570">NCT01038570</a></p

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Étude de l'évolution du jeu lors d'une prise en charge éducative en autisme (progrès et enjeux)

TOULOUSE2-BUC Mirail (315552102) / SudocSudocFranceF

Prader-Willi Syndrome as a Model of Human Hyperphagia

International audienc

Face processing and exploration of social signals in Prader-Willi syndrome: a genetic signature

International audienc

A study of voice and non-voice processing in Prader-Willi syndrome

International audiencePrader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. Itmanifests itself in endocrine and cognitive problems, including highly pronounced hyperphagia and severe obesity.In many cases, impaired acquisition of social and communication skills leads to autism spectrum features, andindividuals with this syndrome are occasionally diagnosed with autism spectrum disorder (ASD) using specificscales. Given that communicational skills are largely based on vocal communication, it is important to study humanvoice processing in PWS.We were able to examine a large number of participants with PWS (N = 61) recruited from France’s nationalreference center for PWS and other hospitals. We tested their voice and nonvoice recognition abilities, as well astheir ability to distinguish between voices and nonvoices in a free choice task. We applied the hierarchical driftdiffusion model (HDDM) with Bayesian estimation to compare decision-making in participants with PWS andcontrols. We found that PWS participants were impaired on both voice and nonvoice processing, but displayed acompensatory ability to perceive voices. Participants with uniparental disomy had poorer voice and nonvoiceperception than participants with a deletion on chromosome 15. The HDDM allowed us to demonstrate thatparticipants with PWS need to accumulate more information in order to make a decision, are slower at decision-making, and are predisposed to voice perception, albeit to a lesser extent than controls. The categorization of voices and nonvoices is generally preserved in participants with PWS, thoughthis may not be the case for the lowest I