1. Adviento B, Corbin IL, Widjaja F, Desachy G, Enrique N, Rosser T, Risi S, Marco EJ, Hendren RL, Bearden CE, Rauen KA, Weiss LA. {{Autism traits in the RASopathies}}. {Journal of medical genetics}. 2013 Oct 7.
BACKGROUND: Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. METHODS: We examined the association of autism traits with NF1, NS, CS and CFC, comparing affected probands with unaffected sibling controls and subjects with idiopathic ASDs using the qualitative Social Communication Questionnaire (SCQ) and the quantitative Social Responsiveness Scale (SRS). RESULTS: Each of the four major RASopathies showed evidence for increased qualitative and quantitative autism traits compared with sibling controls. Further, each RASopathy exhibited a distinct distribution of quantitative social impairment. Levels of social responsiveness show some evidence of correlation between sibling pairs, and autism-like impairment showed a male bias similar to idiopathic ASDs. CONCLUSIONS: Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs.
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2. Brock J. {{Connectivity and cognition in autism spectrum disorders: Where are the links?}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2013 Oct 7.
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3. Chang YC, Laugeson EA, Gantman A, Ellingsen R, Frankel F, Dillon AR. {{Predicting treatment success in social skills training for adolescents with autism spectrum disorders: The UCLA Program for the Education and Enrichment of Relational Skills}}. {Autism}. 2013 Oct 9.
This study seeks to examine the predictors of positive social skills outcomes from the University of California, Los Angeles Program for the Education and Enrichment of Relational Skills, an evidence-based parent-assisted social skills program for high-functioning middle school and high school adolescents with autism spectrum disorders. The results revealed that adolescents with higher parent-reported baseline social skills and lower self-reported perceived social functioning demonstrated greater improvement in social skills following the intervention.
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4. Leonard HC, Bedford R, Charman T, Elsabbagh M, Johnson MH, Hill EL, The Bt. {{Motor development in children at risk of autism: A follow-up study of infant siblings}}. {Autism}. 2013 Oct 7.
Recently, evidence of poor or atypical motor skills in autism spectrum disorder has led some to argue that motor impairment is a core feature of the condition. The current study uses a longitudinal prospective design to assess the development of motor skills of 20 children at increased risk of developing autism spectrum disorder, who were recruited and tested at 9 and 40 months of age, on the basis of having an older sibling diagnosed with the condition. All children completed a range of motor, face processing, IQ and diagnostic assessments at a follow-up visit (aged 5-7 years), providing a detailed profile of development in this group from a number of standardised, parental report and experimental measures. A higher proportion of children than expected demonstrated motor difficulties at the follow-up visit and those highlighted by parental report as having poor motor skills as infants and toddlers were also more likely to have lower face processing scores and elevated autism-related social symptoms at 5-7 years, despite having similar IQ levels. These data lend support to the argument that early motor difficulties may be a risk factor for later motor impairment as well as differences in social communication and cognition, traits that are related to autism spectrum disorder.
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5. May T, Cornish K, Rinehart N. {{Does Gender Matter? A One Year Follow-up of Autistic, Attention and Anxiety Symptoms in High-Functioning Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2013 Oct 9.
Gender differences in autism spectrum disorder (ASD) symptoms and associated problem behaviours over development may provide clues regarding why more males than females are diagnosed with ASD. Fifty-six high-functioning children with ASD, and 44 typically developing controls, half of the participants female, were assessed at baseline (aged 7-12 years) and one-year later, collecting measures of autism, attention and anxiety symptoms, school placement and support information. Findings indicated no gender differences in autistic symptoms. Males were more hyperactive and received more integration-aide support in mainstream schools, and females were more socially anxious. Overall, similar gender profiles were present across two time points. Lower hyperactivity levels in females might contribute to their under-identification. Implications are discussed using a biopsychosocial model of gender difference.
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6. McConachie H, McLaughlin E, Grahame V, Taylor H, Honey E, Tavernor L, Rodgers J, Freeston M, Hemm C, Steen N, Le Couteur A. {{Group therapy for anxiety in children with autism spectrum disorder}}. {Autism}. 2013 Oct 7.
Aim:To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot randomised controlled trial.Method:A total of 32 children aged 9-13 years were randomised to immediate or delayed therapy using the ‘Exploring Feelings’ manual (Attwood, 2004). Child and parent groups were run in parallel, for seven weekly sessions, under the supervision of experienced psychologists. The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months.Results:Children met diagnostic criteria for 1-6 anxiety disorders (median 3). At end point, both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms. Fidelity of delivery of the group therapy was high, and attendance was 91%.Conclusions:This pilot trial established that children and families were willing to be recruited and randomised, the outcome measures were acceptable, the format and content of the groups were feasible within UK child and adolescent mental health services, the intervention was appreciated by families and attrition was very small.
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7. Oldenburg AR, Delbarre E, Thiede B, Vigouroux C, Collas P. {{Deregulation of Fragile X-related protein 1 by the lipodystrophic lamin A p.R482 W mutation elicits a myogenic gene expression program in preadipocytes}}. {Human molecular genetics}. 2013 Oct 9.
The nuclear lamina is implicated in the regulation of various nuclear functions. Several laminopathy-causing mutations in the LMNA gene, notably the p.R482 W substitution linked to familial partial lipodystrophy type 2 (FPLD2), are clustered in the immunoglobulin fold of lamin A. We report a functional association between lamin A and Fragile X-related protein 1 (FXR1P), a protein of the Fragile X-related family involved in Fragile X syndrome. Searching for proteins differentially interacting with the immunoglobulin fold of wild-type and R482 W mutant lamin A, we identify FXR1P as a novel component of lamin A protein network. The p.R482 W mutation abrogates interaction of FXR1P with lamin A. Fibroblasts from FPLD2 patients display elevated levels of FXR1P and delocalized FXR1P. In human adipocyte progenitors, deregulation of lamin A expression leads to FXR1P up-regulation, impairment of adipogenic differentiation and induction of myogenin expression. FXR1P overexpression also stimulates a myogenic gene expression program in these cells. Our results demonstrate a cross-talk between proteins hitherto implicated in two distinct mesodermal pathologies. We propose a model where the FPLD2 lamin A p.R482 W mutation elicits, through up-regulation of FXR1P, a remodeling of an adipogenic differentiation program into a myogenic program.
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8. Plavnick JB, Hume KA. {{Observational learning by individuals with autism: A review of teaching strategies}}. {Autism}. 2013 Oct 7.
Observational learning is the process used to explain the acquisition of novel behaviors or performance of previously acquired behaviors under novel conditions after observing the behavior of another person and the consequences that follow the behavior. Many learners with autism do not attend to environmental stimuli at a level sufficient to learn a range of prosocial behaviors through observation of others. Modeling, group or dyadic instruction, and explicit observation training can improve the extent to which individuals with autism learn through observation. This article reviews previous research that involved observational learning by individuals with autism and outlines future research that could benefit instructional practices.
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9. Rangasamy S, D’Mello SR, Narayanan V. {{Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders}}. {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}. 2013 Oct 9.
Epigenetic marks are modifications of DNA and histones. They are considered to be permanent within a single cell during development, and are heritable across cell division. Programming of neurons through epigenetic mechanisms is believed to be critical in neural development. Disruption or alteration in this process causes an array of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Recent studies have provided evidence for an altered epigenetic landscape in ASDs and demonstrated the central role of epigenetic mechanisms in their pathogenesis. Many of the genes linked to the ASDs encode proteins that are involved in transcriptional regulation and chromatin remodeling. In this review we highlight selected neurodevelopmental disorders in which epigenetic dysregulation plays an important role. These include Rett syndrome, fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each of these disorders, we discuss how advances in our understanding of epigenetic mechanisms may lead to novel therapeutic approaches.
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10. Sharp WG, Burrell TL, Jaquess DL. {{The Autism MEAL Plan: A parent-training curriculum to manage eating aversions and low intake among children with autism}}. {Autism}. 2013 Oct 7.
Feeding problems represent a frequent concern reported by caregivers of children with autism spectrum disorders, and growing evidence suggests atypical patterns of intake may place this population at risk of nutritional and/or related medical issues, including chronic vitamin and mineral deficiencies, poor bone growth, and obesity. This combination of factors emphasizes a clear need to identify and disseminate evidence-based treatment of feeding problems associated with autism spectrum disorders. Behavioral intervention represents an effective treatment for chronic feeding concerns in this population; however, evidence has largely been established with trained therapists working in highly structured settings. This pilot study seeks to fill this gap in the literature by describing and evaluating the Autism MEAL Plan, a behaviorally based parent-training curriculum to address feeding problems associated with autism spectrum disorders. We assessed the feasibility of the intervention in terms of program content and study protocol (e.g. recruitment and retention of participants, assessment procedures), as well as efficacy in terms of changes in feeding behaviors. A total of 10 families participated in the treatment condition, and the program was evaluated using a waitlist control design (n = 9), representing the first randomized-control study of a feeding intervention in autism spectrum disorders. Results provide provisional support regarding the utility of the program, including high social validity, parent perception of effectiveness, and reduced levels of caregiver stress following intervention. Implications, limitations, and future directions for this line of research are discussed.
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11. Siller M, Reyes N, Hotez E, Hutman T, Sigman M. {{Longitudinal change in the use of services in autism spectrum disorder: Understanding the role of child characteristics, family demographics, and parent cognitions}}. {Autism}. 2013 Oct 9.
The aim of this study was to identify child characteristics, family demographics, and parent cognitions that may affect access to early intervention, special education, and related services. The sample included 70 families of young children with autism spectrum disorders. All parents were enrolled in a short education program, providing them with basic information and resources on advocating for a young child with autism spectrum disorders (Parent Advocacy Coaching). Longitudinal change in children’s intervention program in the community was evaluated over a period of about 27 months, starting 12 months prior to enrollment in Parent Advocacy Coaching. Results revealed large individual differences in the intensity of children’s individual and school-based services. Despite this variability, only two child characteristics (age, gender) emerged as independent predictors. In contrast, the intensity of children’s intervention programs was independently predicted by a broad range of demographic characteristics, including parental education, child ethnicity and race, and family composition. Finally, even after child characteristics and family demographics were statistically controlled, results revealed associations between specific parental cognitions (parenting efficacy, understanding of child development) and the subsequent rate of change in the intensity of children’s intervention programs. Implications for improving educational programs that aim to enhance parent advocacy are discussed.
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12. Steinman G, Mankuta D. {{Breastfeeding as a possible deterrent to autism – A clinical perspective}}. {Medical hypotheses}. 2013 Sep 20.
The emergence of autism in young children appears to result from dysmyelination of brain neurons, related to inadequate supply of insulin-like growth factor (IGF) in the newborn. This report is intended to bring together relevant observations from prior research to develop a new, innovative hypothesis to elucidate the mechanism underlying autism development. The deficiency of IGF in affected infants may be due to a combination of genetic and environmental factors yet to be determined. If this hypothesis is correct, breastfeeding in particular could increase IGF levels, thereby compensating for an inborn deficiency of the growth factor.
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13. Tebartz van Elst L, Pick M, Biscaldi M, Fangmeier T, Riedel A. {{High-functioning autism spectrum disorder as a basic disorder in adult psychiatry and psychotherapy: psychopathological presentation, clinical relevance and therapeutic concepts}}. {European archives of psychiatry and clinical neuroscience}. 2013 Oct 9.
Autism spectrum disorder (ASD) is characterized by deficits in social cognition and competence, communication, highly circumscribed interests and a strong desire for routines. Besides, there are specific abnormalities in perception and language. Typical symptoms are already present in early childhood. Traditionally autism has been regarded as a severe form of neurodevelopmental disorder which goes along with overtly abnormal language, learning difficulties and low IQ in the majority of cases. However, over the last decades, it has become clear that there are also many patients with high-functioning variants of ASD. These are patients with normal language at a superficial level of description and normal and sometimes above average intelligence. In high-functioning variants of the disease, they may run unrecognized until late in adult life. High-functioning ASD is associated with a very high prevalence of comorbid classical psychiatric disorders such as depression, anxiety, ADHD, tics, psychotic symptoms or emotionally unstable syndromes. In many such cases, there is a causal relationship between ASD and the comorbid psychiatric conditions in that the specific ASD symptoms result in chronic conflicts, misunderstandings and failure in private and vocational relationships. These problems in turn often lead to depression, anxiety and sometimes psychosis-like stress reactions. In this constellation, ASD has to be regarded as a basic disorder with causal relevance for secondary psychiatric syndromes. In this paper, we summarize the classical presentation of high-functioning ASD in adult psychiatry and psychotherapy and suggest a nosological model to classify different ASD conditions instead. To conclude, we outline first treatment concepts in out- and in-patient settings.
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14. Thabet EM. {{Ocular vestibular evoked myogenic potentials n10 response in autism spectrum disorders children with auditory hypersensitivity: an indicator of semicircular canal dehiscence}}. {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology – Head and Neck Surgery}. 2013 Oct 8.
Sensitivity to sound is one of the most commonly reported challenges in ASD. No compelling evidence shows that hearing of ASD individuals differs physiologically from normal peers. Superior semicircular canal dehiscence was found to be more common in ASD children with auditory hypersensitivity (29 %) by means of high-resolution CT scan than the reported (14 %) in normal pediatric population by other investigators. The increased prevalence of radiographic dehiscence might be due to inability of CT scan to visualize immature bone. We wished to determine whether ocular vestibular evoked myogenic potentials in ASD children with auditory hypersensitivity produces similar responses to those obtained in adult superior canal dehiscence, and whether it could help differentiate radiographic dehiscence due to bone immaturity from true canal dehiscence syndrome. A prospective study on 14 ASD children complaining of auditory hypersensitivity served as the study group. 15 ASD children without auditory hypersensitivity, age and gender matched, served as a control group. oVEMP and high-resolution CT scan of petrous and temporal bone were performed to all participants. Mean amplitude of n10 was 1.83 +/- 0.11 and 1.79 +/- 0.09 muV in the control group with mean peak latency of 9.79 +/- 0.42 and 9.77 +/- 0.30 ms for the right and left ears, respectively. Asymmetry ratio was 2.04 +/- 1.37. In the study group, the mean amplitude of n10 was 2.07 +/- 0.46 and 1.89 +/- 0.30 muV, with mean peak latency of 9.52 +/- 0.33 and 9.59 +/- 0.21 ms for the right and left ears, respectively, with asymmetry 5.23 +/- 6.93 %. No statistically significant difference was observed for the studied parameters. In the study group, the number of ears showing an augmented amplitude (>2SD) of n10 was (N = 5). Furthermore, the study group demonstrated a radiographic SSCD in 6 ears. n10 was normal in the control group while radiographic SSCD was observed in 3 of them. Conclusion: oVEMPs show diagnostic ability in differentiating ASD children complaining of auditory hypersensitivity due to superior canal dehiscence from those with radiographic dehiscence only due to bone immaturity or atypical cortical development.
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15. Yao B, Lin L, Street RC, Zalewski ZA, Galloway JN, Wu H, Nelson DL, Jin P. {{Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X-associated tremor/ataxia syndrome}}. {Human molecular genetics}. 2013 Oct 9.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder in which patients carry premutation alleles of 55-200 CGG repeats in the FMR1 gene. To date, whether alterations in epigenetic regulation modulate FXTAS has gone unexplored. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine (5mC) by the ten-eleven translocation (TET) family of proteins, has been found recently to play key roles in neuronal functions. Here we undertook genome-wide profiling of cerebellar 5hmC in a FXTAS mouse model (rCGG mice) and found that rCGG mice at 16 weeks showed overall reduced 5hmC levels genome-wide compared to age-matched wild-type littermates. However, we also observed gain-of-5hmC regions in repetitive elements, as well as in cerebellum-specific enhancers, but not in general enhancers. Genomic annotation and motif prediction of wild-type- and rCGG-specific differential 5-hydroxymethylated regions (DhMRs) revealed their high correlation with genes and transcription factors that are important in neuronal developmental and functional pathways. DhMR-associated genes partially overlapped with genes that were differentially associated with ribosomes in CGG mice identified by bacTRAP ribosomal profiling. Taken together, our data strongly indicate a functional role for 5hmC-mediated epigenetic modulation in the etiology of FXTAS, possibly through the regulation of transcription.
