Publications by authors named "Bernadette Roge"

29 Publications

  • Page 1 of 1

Real-World Experiences in Autistic Adult Diagnostic Services and Post-diagnostic Support and Alignment with Services Guidelines: Results from the ASDEU Study.

J Autism Dev Disord 2021 Jan 27. Epub 2021 Jan 27.

Departamento de Personalidad, Evaluación y Tratamiento Psicológicos, INICO-Instituto Universitario de Integración en la Comunidad University of Salamanca, Salamanca, Spain.

Research providing an evidence-base for autistic adult services is sparse. The Autism Spectrum Disorders in the European Union (ASDEU) network implemented an on-line survey to determine gaps in autistic adult diagnostic evaluation and post-diagnostic support services. More than 55% in all groups experienced most of the recommended features for diagnostic evaluation for autistic adults. In contrast, < 2% of adults or carers, and < 21% of professionals experienced each of the recommended features for post-diagnostic support. In contrast to 61% of professionals, only about 30% of autistic adults and carers had knowledge of good local services models for autism diagnosis in adulthood. There are major differences between good practice guidelines for diagnostic and post-diagnostic care for autistic adults, and what is actually experienced by services users and professionals.
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http://dx.doi.org/10.1007/s10803-021-04873-5DOI Listing
January 2021

Early Detection, Diagnosis and Intervention Services for Young Children with Autism Spectrum Disorder in the European Union (ASDEU): Family and Professional Perspectives.

J Autism Dev Disord 2020 Sep;50(9):3380-3394

CERPPS, Université Toulouse Jean-Jaurès, Toulouse, France.

Early services for ASD need to canvas the opinions of both parents and professionals. These opinions are seldom compared in the same research study. This study aims to ascertain the views of families and professionals on early detection, diagnosis and intervention services for young children with ASD. An online survey compiled and analysed data from 2032 respondents across 14 European countries (60.9% were parents; 39.1% professionals). Using an ordinal scale from 1 to 7, parents' opinions were more negative (mean = 4.6; SD 2.2) compared to those of professionals (mean = 4.9; SD 1.5) when reporting satisfaction with services. The results suggest services should take into account child's age, delays in accessing services, and active stakeholders' participation when looking to improve services.
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http://dx.doi.org/10.1007/s10803-019-04253-0DOI Listing
September 2020

Building a theoretical framework for autism spectrum disorders screening instruments in Europe.

Child Adolesc Ment Health 2018 Nov 22;23(4):359-367. Epub 2017 Dec 22.

Institute of Community Integration (INICO), Faculty of Education, University of Salamanca, Salamanca, Spain.

Background: This study addresses the need for a theoretical base to develop more effective early autism spectrum disorders (ASD) detection tools. The structure that underlies early ASD detection is explored by evaluating the opinions of experts on ASD screening tools currently used in Europe.

Method: A process of face and content validity was performed. First, the best constructs were selected from the relevant tests: Checklist for Early Signs of Developmental Disorders (CESDD), Checklist for Autism in Toddlers (CHAT), Early Screening of Autistic Traits Questionnaire (ESAT), Modified Checklist for Autism in Toddlers (M-CHAT), Social Communication Questionnaire (SCQ) and Communication and Symbolic Behaviour Scales Developmental Profile (CSBS-DP). The diagnostic content validity model by Fehring (1986, 1994) was adapted to make the selection. Afterwards, the items, taken from these tests, were selected to fit into each construct, using the same methodology.

Results: Twelve of the 18 constructs were selected by the experts and 11 items were chosen from a total of 130, reduced to eight after eliminating tautologies.

Conclusions: Mapping these constructs and items on to the DSM-5 diagnostic criteria for ASD indicated good face and content validity. Results of this research will contribute to efforts to improve early ASD screening instruments and identify the key behaviours that experts in ASD see as the most relevant for early detection.
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http://dx.doi.org/10.1111/camh.12256DOI Listing
November 2018

Analysis of shared heritability in common disorders of the brain.

Science 2018 06;360(6395)

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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http://dx.doi.org/10.1126/science.aap8757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097237PMC
June 2018

The French Version of the Modified-Checklist for Autism in Toddlers (M-CHAT): A Validation Study on a French Sample of 24 Month-Old Children.

J Autism Dev Disord 2017 Feb;47(2):297-304

CERPPS, Universite de Toulouse, UT2J, 5, allées Antonio Machado, 31058, Toulouse Cedex9, France.

Early ASD screening has the potential to reduce delays between initial parental concerns and diagnosis, and promote early intervention. The aim of this study was to validate the M-CHAT on a French population sample of 24 month-old children. This study included a low-risk sample of 1227 children. A total of 20 children screened positive on the M-CHAT. Twelve out of 20 of these children received a diagnosis of ASD at 36 months, yielding a PPV of 0.60. These results add to the evidence that the M-CHAT is a useful screening instrument and further demonstrates the importance of the follow-up interview in primary care settings. This study provides French practitioners with guidelines regarding the use of the M-CHAT at 24 months.
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http://dx.doi.org/10.1007/s10803-016-2950-yDOI Listing
February 2017

Attitudes of the autism community to early autism research.

Autism 2017 01 14;21(1):61-74. Epub 2016 Mar 14.

Norwegian Institute of Public Health, Norway.

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.
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http://dx.doi.org/10.1177/1362361315626577DOI Listing
January 2017

Intact perception but abnormal orientation towards face-like objects in young children with ASD.

Sci Rep 2016 Feb 25;6:22119. Epub 2016 Feb 25.

URI Octogone, University of Toulouse, 5 Allée Antonio Machado, 31058 Toulouse Cedex 9, France.

There is ample behavioral evidence of diminished orientation towards faces as well as the presence of face perception impairments in autism spectrum disorder (ASD), but the underlying mechanisms of these deficits are still unclear. We used face-like object stimuli that have been shown to evoke pareidolia in typically developing (TD) individuals to test the effect of a global face-like configuration on orientation and perceptual processes in young children with ASD and age-matched TD controls. We show that TD children were more likely to look first towards upright face-like objects than children with ASD, showing that a global face-like configuration elicit a stronger orientation bias in TD children as compared to children with ASD. However, once they were looking at the stimuli, both groups spent more time exploring the upright face-like object, suggesting that they both perceived it as a face. Our results are in agreement with abnormal social orienting in ASD, possibly due to an abnormal tuning of the subcortical pathway, leading to poor orienting and attention towards faces. Our results also indicate that young children with ASD can perceive a generic face holistically, such as face-like objects, further demonstrating holistic processing of faces in ASD.
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http://dx.doi.org/10.1038/srep22119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766445PMC
February 2016

The Importance of Networking in Autism Gaze Analysis.

PLoS One 2015 23;10(10):e0141191. Epub 2015 Oct 23.

URI Octogone, University Toulouse Jean Jaurès, Toulouse, France; Harvard Medical School / MGH / MIT, Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Gillberg Neuropsychiatry Center, University of Gothenburg, Gothenburg, Sweden.

Visual scanning of faces in individuals with Autism Spectrum Disorder (ASD) has been intensively studied using eye-tracking technology. However, most of studies have relied on the same analytic approach based on the quantification of fixation time, which may have failed to reveal some important features of the scanning strategies employed by individuals with ASD. In the present study, we examined the scanning of faces in a group of 20 preschoolers with ASD and their typically developing (TD) peers, using both classical fixation time approach and a new developed approach based on transition matrices and network analysis. We found between group differences in the eye region in terms of fixation time, with increased right eye fixation time for the ASD group and increased left eye fixation time for the TD group. Our complementary network approach revealed that the left eye might play the role of an anchor in the scanning strategies of TD children but not in that of children with ASD. In ASD, fixation time on the different facial parts was almost exclusively dependent on exploratory activity. Our study highlights the importance of developing innovative measures that bear the potential of revealing new properties of the scanning strategies employed by individuals with ASD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619728PMC
June 2016

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

Autism Res 2015 Oct 10;8(5):522-33. Epub 2015 May 10.

From University of Oxford Department of Psychiatry, UK.

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP.
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http://dx.doi.org/10.1002/aur.1466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690162PMC
October 2015

Use of early intervention for young children with autism spectrum disorder across Europe.

Autism 2016 Feb 27;20(2):233-49. Epub 2015 Apr 27.

Centro Hospitalar e Universitário de Coimbra, Portugal.

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable variation in use of interventions, and in some countries more than 20% of children received no intervention at all. The most frequently reported interventions were speech and language therapy (64%) and behavioural, developmental and relationship-based interventions (55%). In some parts of Europe, use of behavioural, developmental and relationship-based interventions was associated with higher parental educational level and time passed since diagnosis, rather than with child characteristics. These findings highlight the need to monitor use of intervention for children with autism spectrum disorder in Europe in order to contrast inequalities.
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http://dx.doi.org/10.1177/1362361315577218DOI Listing
February 2016

Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers: Application in a Non-US Sample of 1,104 Children.

J Autism Dev Disord 2015 Jul;45(7):2076-91

Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands,

The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord, J Autism Dev Disord 42(1):82-93, 2012) in a non-US sample from ten sites in nine countries (n = 1,104). The construct validity indicated a good fit of the algorithms. The diagnostic validity was lower, with satisfactorily high specificities but moderate sensitivities. Young children with clinical ASD and lower language ability were largely in the mild-to-moderate or moderate-to-severe concern ranges of the ADI-R, nearly half of the older and phrase speech ASD-group fell into the little-to-no concern range. Although broadly the findings support the toddler algorithms, further work is required to understand why they might have different properties in different samples to further inform research and clinical use.
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http://dx.doi.org/10.1007/s10803-015-2372-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471312PMC
July 2015

Both dog and human faces are explored abnormally by young children with autism spectrum disorders.

Neuroreport 2014 Oct;25(15):1237-41

aURI Octogone-CERPP, University of Toulouse, France bHarvard Medical School/MGH/MIT, Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, USA cGillberg Neuropsychiatry Center, Gothenburg University, Sweden.

When looking at faces, typical individuals tend to have a right hemispheric bias manifested by a tendency to look first toward the left visual hemifield. Here, we tested for the presence of this bias in young children with autism spectrum disorders (ASD) for both human and dog faces. We show that children with ASD do not show a left visual hemifield (right hemispheric) bias for human faces. In addition, we show that this effect extends to faces of dogs, suggesting that the absence of bias is not specific to human faces, but applies to all faces with the first-order configuration, pointing to an anomaly at an early stage of visual analysis of faces. The lack of right hemispheric dominance for face processing may reflect a more general disorder of cerebral specialization of social functions in ASD.
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http://dx.doi.org/10.1097/WNR.0000000000000257DOI Listing
October 2014

Screening for autism spectrum disorders: state of the art in Europe.

Eur Child Adolesc Psychiatry 2014 Nov 10;23(11):1005-21. Epub 2014 Jun 10.

Institute of Rare Diseases Research (Instituto de Investigación de Enfermedades Raras, IIER), Carlos III Institute of Health, Madrid, Spain,

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies' findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures.
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http://dx.doi.org/10.1007/s00787-014-0555-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229652PMC
November 2014

Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.

Am J Hum Genet 2014 May 24;94(5):677-94. Epub 2014 Apr 24.

Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland; Children's University Hospital Temple Street, Dublin 1, Ireland.

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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http://dx.doi.org/10.1016/j.ajhg.2014.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067558PMC
May 2014

Visual social attention in autism spectrum disorder: insights from eye tracking studies.

Neurosci Biobehav Rev 2014 May 30;42:279-97. Epub 2014 Mar 30.

URI Octogone-CERPP, University of Toulouse, 5 allée Antonio Machado, 31058 Toulouse Cedex 9, France. Electronic address:

We review different aspects of visual social attention in autism spectrum disorders (ASD) from infancy to adulthood in light of the eye-tracking literature. We first assess the assumption that individuals with ASD demonstrate a deficit in social orienting together with decreased attention to socially relevant stimuli such as faces compared to TD individuals. Results show that social orienting is actually not qualitatively impaired and that decreased attention to faces does not generalized across contexts. We also assess the assumption that individuals with ASD demonstrate excess mouth and diminished eye gaze compared to TD individuals. We find that this assumption receives little support across ages and discuss some factors that might have initially lead to this conjecture. We report that the assessment of the ability to follow the direction of another person's gaze needs to be further examined and that eye-tracking studies add to the evidence that individuals with ASD demonstrate difficulties in interpreting gaze cues. Finally, we highlight innovative data acquisition and analyses that are increasingly shedding light on the more subtle nature of the profound social difficulties experienced by individuals with ASD.
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http://dx.doi.org/10.1016/j.neubiorev.2014.03.013DOI Listing
May 2014

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

Hum Mol Genet 2012 Nov 26;21(21):4781-92. Epub 2012 Jul 26.

Autism Genetics Group, Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Ireland.

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< 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.
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http://dx.doi.org/10.1093/hmg/dds301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471395PMC
November 2012

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

Hum Genet 2012 Apr 14;131(4):565-79. Epub 2011 Oct 14.

School of Medicine and Medical Science University College, Dublin, Ireland.

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.
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http://dx.doi.org/10.1007/s00439-011-1094-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303079PMC
April 2012

Blame and forgiveness judgements among children, adolescents and adults with autism.

Autism 2011 Nov 29;15(6):702-12. Epub 2011 Jun 29.

Mirail University, Toulouse, France.

We compared the capacity of children, adolescents and adults with and without autism to use (a) intent and severity of consequences information for attributing blame to an offender, and (b) intent and apologies information for inferring willingness to forgive. Participants were presented with two sets of six scenarios obtained by combination of intent and severity (or apology) information, and instructed to indicate appropriate levels of blame (or willingness to forgive). In the blame condition, persons with autism were able to consistently use intent information but not to the same degree as their comparison counterparts. In the forgiveness condition, intent was not taken into account for judging by persons with autism, irrespective of their age.
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http://dx.doi.org/10.1177/1362361310394219DOI Listing
November 2011

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.

Orphanet J Rare Dis 2011 Jun 24;6:47. Epub 2011 Jun 24.

Centre de Référence du Syndrome de Prader-Willi, Division of Endocrinology, Genetics, Gynaecology and Bone Diseases, Hôpital des Enfants, Toulouse, France.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial Registration Number: ClinicalTrials.gov: NCT01038570.
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http://dx.doi.org/10.1186/1750-1172-6-47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141367PMC
June 2011

Early processing of emotional faces in children with autism: An event-related potential study.

J Exp Child Psychol 2011 Aug 1;109(4):430-44. Epub 2011 Apr 1.

UMRS Inserm U930, CNRS ERL 3106, Université François Rabelais de Tours, CHRU de Tours, 37044 Tours, France.

Social deficits are one of the most striking manifestations of autism spectrum disorders (ASDs). Among these social deficits, the recognition and understanding of emotional facial expressions has been widely reported to be affected in ASDs. We investigated emotional face processing in children with and without autism using event-related potentials (ERPs). High-functioning children with autism (n=15, mean age=10.5±3.3 years) completed an implicit emotional task while visual ERPs were recorded. Two groups of typically developing children (chronological age-matched and verbal equivalent age-matched [both ns=15, mean age=7.7±3.8 years]) also participated in this study. The early ERP responses to faces (P1 and N170) were delayed, and the P1 was smaller in children with autism than in typically developing children of the same chronological age, revealing that the first stages of emotional face processing are affected in autism. However, when matched by verbal equivalent age, only P1 amplitude remained affected in autism. Our results suggest that the emotional and facial processing difficulties in autism could start from atypicalities in visual perceptual processes involving rapid feedback to primary visual areas and subsequent holistic processing.
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http://dx.doi.org/10.1016/j.jecp.2011.02.001DOI Listing
August 2011

A genome-wide scan for common alleles affecting risk for autism.

Hum Mol Genet 2010 Oct 27;19(20):4072-82. Epub 2010 Jul 27.

Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Ireland.

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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http://dx.doi.org/10.1093/hmg/ddq307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947401PMC
October 2010

PET scan perfusion imaging in the Prader-Willi syndrome: new insights into the psychiatric and social disturbances.

J Cereb Blood Flow Metab 2011 Jan 30;31(1):275-82. Epub 2010 Jun 30.

INSERM, Imagerie cérébrale et handicaps neurologiques UMR 825, Toulouse, France.

The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.
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http://dx.doi.org/10.1038/jcbfm.2010.87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049491PMC
January 2011

Functional impact of global rare copy number variation in autism spectrum disorders.

Nature 2010 Jul 9;466(7304):368-72. Epub 2010 Jun 9.

The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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http://dx.doi.org/10.1038/nature09146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021798PMC
July 2010

Recognition of emotional and nonemotional facial expressions: a comparison between Williams syndrome and autism.

Res Dev Disabil 2009 Sep-Oct;30(5):976-85. Epub 2009 Mar 14.

Centre de Recherches en Psychologie, Cognition et Communication (EA 1285), Université de Rennes 2, France.

The aim of our study was to compare two neurodevelopmental disorders (Williams syndrome and autism) in terms of the ability to recognize emotional and nonemotional facial expressions. The comparison of these two disorders is particularly relevant to the investigation of face processing and should contribute to a better understanding of social behaviour and social cognition. Twelve participants with WS (from 6;1 to 15 years) and twelve participants with autism (from 4;9 to 8 years) were matched on verbal mental age. Their performances were compared with those of twelve typically developing controls matched on verbal mental age (from 3;1 to 9;2). A set of five tasks assessing different dimensions of emotional and nonemotional facial recognition were administered. Results indicated that recognition of emotional facial expressions is more impaired in Williams syndrome than in autism. Our study comparing Williams syndrome and autism over a small age range highlighted two distinct profiles which call into question the relationships between social behaviour/cognition and emotion perception.
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http://dx.doi.org/10.1016/j.ridd.2009.02.002DOI Listing
August 2009

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

Nat Genet 2007 Mar 18;39(3):319-28. Epub 2007 Feb 18.

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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http://dx.doi.org/10.1038/ng1985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867008PMC
March 2007

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

Nat Genet 2007 Jan 17;39(1):25-7. Epub 2006 Dec 17.

Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.
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http://dx.doi.org/10.1038/ng1933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082049PMC
January 2007

Increased perception of loudness in autism.

Hear Res 2004 Dec;198(1-2):87-92

Laboratoire de Neurophysiologie et Neuropsychologie, Faculté de médecine Timone, Inserm EMI-U 9926, Université de la Méditerrancée, 27, Bd Jean Moulin 13385, Marseille Cedex 5, France.

Clinical reports on autism describe abnormal responses to auditory stimuli such as intolerance to sounds. The present study assessed subjective perception of loudness in subjects with autism compared to healthy controls, using two psychoacoustic tests. First, the auditory dynamic range was evaluated at six different tone frequencies. Secondly, loudness growth as a function of the intensity level of a 1 kHz tone was estimated. Verbal responses from a group of 11 children and adolescents with autism were compared to responses of 11 age- and gender- matched healthy controls. Smaller auditory dynamic ranges were found in the autistic group than in the control group, as well as increased perception of loudness, indicating hyperacusis in subjects with autism.
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http://dx.doi.org/10.1016/j.heares.2004.07.006DOI Listing
December 2004

The mental adjustment to cancer (MAC) scale: French replication and assessment of positive and negative adjustment dimensions.

Psychooncology 2003 Jan-Feb;12(1):8-23

Unité de Psycho-Oncologie, Institut Curie- 26, rue d'Ulm, Paris, France.

The Mental Adjustment to Cancer (MAC) scale was validated on a heterogeneous French sample of 317 cancer patients. Internal consistency was satisfactory for the original subscales (alpha coefficients=0.62-0.80), except for the Fatalism subscale (alpha=0.40). The intercorrelations of the subscales and the correlations between the subscales and Anxiety and Depression criteria were congruent with the values reported in the literature. Multidimensional Scaling revealed three positive and three negative subsets of items revealing adjustment to cancer. Congeneric factor analysis of the subsets was performed with LISREL 8.3 and only three of them (after discarding certain items) were retained: Fighting Spirit (FS) Hopelessness/Helplessness (HH) and Anxious Preoccupation (AP). A confirmatory hierarchical factor analysis on the 21 items included showed that FS measured positive adjustment to cancer and HH and AP measured negative adjustment. A differential adjustment hypothesis was proposed in order to explain the stability and instability of the measures of the diverse constructs. The three revised subscales showed the same validity pattern as the corresponding original scales, but the magnitude of the correlations was considerably improved with respect to the original subscales. The practical and the theoretical importance of FS, HH and AP are emphasized.
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http://dx.doi.org/10.1002/pon.634DOI Listing
April 2003