1. Andersen PN, Skogli EW, Hovik KT, Geurts H, Egeland J, Oie M. {{Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: Results from a 2-year longitudinal study}}. {Autism};2014 (Mar 6)
The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder.
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2. Banerjee S, Riordan M, Bhat MA. {{Genetic aspects of autism spectrum disorders: insights from animal models}}. {Front Cell Neurosci};2014;8:58.
Autism spectrum disorders (ASDs) are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development, and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy, and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute toward the formation, stabilization, and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.
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3. Blaser E, Eglington L, Carter AS, Kaldy Z. {{Pupillometry Reveals a Mechanism for the Autism Spectrum Disorder (ASD) Advantage in Visual Tasks}}. {Sci Rep};2014;4:4301.
Research on the neural underpinnings of Autism Spectrum Disorder (ASD) has focussed primarily on impairments of social interaction and communication. Less is known though about the second diagnostic criterion of restricted behaviors and interests. Uniquely in this domain, alongside impairments stands an ‘ASD advantage’ characterised by superior performance on many visual tasks. We recently found that 2-year-olds with ASD dramatically outperform age-matched, typically developing controls on visual search. Here we use task-evoked, phasic pupil responses – a sensitive, involuntary measure of effort and a biomarker of the locus coeruleus-norepinephrine (LC-NE) system’s modulation of attention – to isolate a causal factor: a ‘hyperphasic’ LC-NE system compels (here, advantageously) focussed attention. However, this focussed attention in other contexts may contribute to restricted behaviors and interests.
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4. Frazier TW, Thompson L, Youngstrom EA, Law P, Hardan AY, Eng C, Morris N. {{A Twin Study of Heritable and Shared Environmental Contributions to Autism}}. {J Autism Dev Disord};2014 (Mar 7)
The present study examined genetic and shared environment contributions to quantitatively-measured autism symptoms and categorically-defined autism spectrum disorders (ASD). Participants included 568 twins from the Interactive Autism Network. Autism symptoms were obtained using the Social Communication Questionnaire and Social Responsiveness Scale. Categorically-defined ASD was based on clinical diagnoses. DeFries-Fulker and liability threshold models examined etiologic influences. Very high heritability was observed for extreme autism symptom levels ([Formula: see text]). Extreme levels of social and repetitive behavior symptoms were strongly influenced by common genetic factors. Heritability of categorically-defined ASD diagnosis was comparatively low (.21, 95 % CI 0.15-0.28). High heritability of extreme autism symptom levels confirms previous observations of strong genetic influences on autism. Future studies will require large, carefully ascertained family pedigrees and quantitative symptom measurements.
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5. Janc OA, Muller M. {{The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome}}. {Front Cell Neurosci};2014;8:56.
Rett syndrome (RS) causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2 (methyl-CpG-binding protein 2)-deficient mouse (Mecp2 (-) (/y)) hippocampus confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3-5 h. In Mecp2 (-) (/y) slices this treatment dampened neuronal hyperexcitability, improved synaptic short-term plasticity, and fully restored synaptic long-term potentiation (LTP). Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2 (-) (/y) slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2 (-) (/y) hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves the hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation.
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6. Li J, Zhu L, Gummerum M. {{The relationship between moral judgment and cooperation in children with high-functioning autism}}. {Sci Rep};2014;4:4314.
This study investigated moral judgment in children with high-functioning autism and their cooperation in prisoner’s dilemma game with partners of different moralities. Thirty-eight 6- to 12-year-old high-functioning autistic (HFA) children and 31 typically developing (TD) children were recruited. Children were asked to judge story protagonists’ morality. After making this moral judgment correctly, they were asked to play with the morally nice and the morally naughty child in a repeated prisoner’s dilemma game. Results showed that both HFA and TD children made correct moral judgments, and that HFA children might even have more rigid criteria for what constitutes morally naughty acts. HFA children’s cooperation did not differ depending on the morality of the interaction partner, while TD children showed higher cooperation when interacting with the morally nice than the morally naughty child did. Thus, partner’s morality did influence TD children’s but not HFA children’s subsequent cooperation.
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7. Liu L, Lei J, Sanders SJ, Willsey AJ, Kou Y, Cicek AE, Klei L, Lu C, He X, Li M, Muhle RA, Ma’ayan A, Noonan JP, Sestan N, McFadden KA, State MW, Buxbaum JD, Devlin B, Roeder K. {{DAWN: A framework to identify autism genes and subnetworks using gene expression and genetics}}. {Mol Autism};2014 (Mar 6);5(1):22.
BACKGROUND: emph{De novo} loss-of-function (dnLoF) mutations are found twofold more often in autism spectrum disorder (ASD) probands than their unaffected siblings. Multiple independent dnLoF mutations in the same gene implicate the gene in risk and hence provide a systematic, albeit arduous, path forward for ASD genetics. It is likely that using additional non-genetic data will enhance the ability to identify ASD genes. METHODS: To accelerate the search for ASD genes, we developed a novel algorithm, DAWN, to model two kinds of data: rare variations from exome sequencing and gene co-expression in the mid-fetal prefrontal and motor-somatosensory neocortex, a critical nexus for risk. The algorithm casts the ensemble data as a hidden Markov random field in which the graph structure is determined by gene co-expression and it combines these interrelationships with node-specific observations, namely gene identity, expression, genetic data and the estimated effect on risk. RESULTS: Using currently available genetic data and a specific developmental time period for gene co-expression, DAWN identified 127 genes that plausibly affect risk, and a set of likely ASD subnetworks. Validation experiments making use of published targeted resequencing results demonstrate its efficacy in reliably predicting ASD genes. DAWN also successfully predicts known ASD genes, not included in the genetic data used to create the model. CONCLUSIONS: Validation studies demonstrate that DAWN is effective in predicting ASD genes and subnetworks by leveraging genetic and gene expression data. The findings reported here implicate neurite extension and neuronal arborization as risks for ASD. Using DAWN on emerging ASD sequence data and gene expression data from other brain regions and tissues would likely identify novel ASD genes. DAWN can also be used for other complex disorders to identify genes and subnetworks in those disorders.
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8. Matson JL, Goldin RL. {{Diagnosing Young Children with Autism}}. {Int J Dev Neurosci};2014 (Mar 3)
The starting point for any research on Autism Spectrum Disorder (ASD) involves the identification of people who evince the condition. From this point flows research on symptom presentation, genetics, epidemiology, animal models, treatment efficacy, and many other important topics. Major advances have been made in differential diagnosis, particularly with young children. This fact is particularly important since ASD is a life long condition. This review documents recent advances and the current state of research on this topic.
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9. Moul C, Cauchi A, Hawes DJ, Brennan J, Dadds MR. {{Differentiating Autism Spectrum Disorder and Overlapping Psychopathology with a Brief Version of the Social Responsiveness Scale}}. {Child Psychiatry Hum Dev};2014 (Mar 7)
The Social Responsiveness Scale (SRS) is a well-established measure of autism spectrum disorder (ASD), yet it is known to suffer reduced specificity in samples of children with comorbid emotional or behavioural problems. This research examined the specificity of the SRS in children with mixed presentations of internalising and externalising psychopathology and ASD. Participants were 522 (397 male) children aged between 4 and 16 years. The associations between SRS total scores and diagnoses were determined using partial correlations and analyses of variance. A subsample of participants with a single diagnosis was used to identify a subset of questions that distinguished between ASD and all other diagnoses. These items were used to create the 16-item SRS-brief. The SRS was found to have good reliability and sensitivity but poor specificity. The SRS-brief had good psychometric properties and was found to be a more accurate tool for the screening of ASD than the original SRS.
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10. Murshid EZ. {{Diet, oral hygiene practices and dental health in autistic children in riyadh, saudi arabia}}. {Oral Health Dent Manag};2014 (Mar);13(1):91-96.
Studies reporting the dietary habits of children with ASD in relation to dental health are scarce, and similar studies are non-existent in Saudi Arabia. Purpose: to report baseline information about the diet, oral hygiene and dental health of a group of autistic children in Riyadh. Methodology: 450 self-administered cross-sectional questionnaires were distributed to parents of autistic children enrolled in three major autistic rehabilitation centers. Results: parents reported that (70.9%) of the children preferred food that is high in sugar and (96.7%) consumed soft drinks regularly. Parents reported their children brushing once 34.0% or twice 29.0% a day, and 28.8% brushed on an irregular basis. 82.6% of the children had no gingival bleeding during brushing. 51.5% of the children had no previous dental visits or dental treatment, 48.5% had undergone dental treatment using different behavioral management techniques. Conclusion: Children in this study showed frequent consumptions of foods with high sugar contents and soft drinks, which coupled with improper oral hygiene practices and insufficient dental visits, may have contributed to the risk of developing dental caries and teeth erosion. Frequent tooth brushing, low-sugar diets and early dental visits for check-ups and regular fluoride applications are highly recommended for ASD children.
11. Santini AC, Pierantoni GM, Gerlini R, Iorio R, Olabinjo Y, Giovane A, Di Domenico M, Sogos C. {{Glix 13, a New Drug Acting on Glutamatergic Pathways in Children and Animal Models of Autism Spectrum Disorders}}. {Biomed Res Int};2014;2014:234295.
Recently standardized diagnostic instruments have been developed in diagnostic and therapeutic procedures for Autism Spectrumv Disorders (ASD). According to the DSM-5 criteria, individuals with ASD must show symptoms from early childhood. These symptoms are communication deficits and restricted, repetitive patterns of behaviour. It was recently described by Bioinformatic analysis that 99 modified genes were associated with human autism. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor gene family was identified among these. Using ultrasonic vocalizations, it was demonstrated that genetic variation has a direct impact on the expression of social interactions. It has been proposed that specific alleles interact with a social reward process in the adolescent mouse modifying their social interaction and their approach toward each other. In this review we report that the monoclonal antibody-derived tetrapeptide GLYX-13 was found to act as an N-methyl-D-aspartate receptor modulator and possesses the ability to readily cross the blood brain barrier. Treatment with the NMDAR glycine site partial agonist GLYX-13 rescued the deficit in the animal model. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism in autistic children.
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12. Sparaci L, Stefanini S, D’Elia L, Vicari S, Rizzolatti G. {{What and Why Understanding in Autism Spectrum Disorders and Williams Syndrome: Similarities and Differences}}. {Autism Res};2014 (Mar 6)
Children with autism spectrum disorders (ASD) and children with Williams syndrome (WS) show divergent social phenotypes, but also several similarities in their socio-cognitive deficits. Cross-syndrome direct comparisons could lead to a better understanding of mechanisms that determine deficits in social cognition in the two syndromes. A fundamental factor for social cognition is the ability to understand and predict others’ actions (e.g. what action is being done and why it is being done when observing a goal-related act). Here we compared the understanding of others’ actions in children with ASD, WS and in children with typical development. Comprehension of what motor act was being done and of why it was being done was assessed with or without contextual cueing using a computer-based task. The results showed that what understanding was impaired in the WS group, but not in the ASD group, which showed mental-age appropriate performance. Why understanding was impaired in both experimental groups. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
