1. Adayev T, LaFauci G, Dobkin C, Caggana M, Wiley V, Field M, Wotton T, Kascsak R, Nolin SL, Glicksman A, Hosmer N, Brown W. {{Fragile X protein in newborn dried blood spots}}. {BMC Med Genet};2014 (Oct 28);15(1):119.
BackgroundThe fragile X syndrome (FXS) results from mutation of the FMR1 gene that prevents expression of its gene product, FMRP. We previously characterized 215 dried blood spots (DBS) representing different FMR1 genotypes and ages with a Luminex-based immunoassay (qFMRP). We found variable FMRP levels in the normal samples and identified affected males by the drastic reduction of FMRP.MethodsHere, to establish the variability of expression of FMRP in a larger random population we quantified FMRP in 2,000 anonymous fresh newborn DBS. We also evaluated the effect of long term storage on qFMRP by retrospectively assaying 74 aged newborn DBS that had been stored for 7-84 months that included normal and full mutation individuals. These analyses were performed on 3 mm DBS disks. To identify the alleles associated with the lowest FMRP levels in the fresh DBS, we analyzed the DNA in the samples that were more than two standard deviations below the mean.ResultsAnalysis of the fresh newborn DBS revealed a broad distribution of FMRP with a mean approximately 7-fold higher than that we previously reported for fresh DBS in normal adults and no samples whose FMRP level indicated FXS. DNA analysis of the lowest FMRP DBS showed that this was the low extreme of the normal range and included a female carrying a 165 CGG repeat premutation. In the retrospective study of aged newborn DBS, the FMRP mean of the normal samples was less than 30% of the mean of the fresh DBS. Despite the degraded signal from these aged DBS, qFMRP identified the FXS individuals.ConclusionsThe assay showed that newborn DBS contain high levels of FMRP that will allow identification of males and potentially females, affected by FXS. The assay is also an effective screening tool for aged DBS stored for up to four years.
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2. Alderson-Day B. {{Verbal Problem-Solving Difficulties in Autism Spectrum Disorders and Atypical Language Development}}. {Autism Res};2014 (Oct 23)
Children with autism spectrum disorders (ASDs) adopt less efficient strategies than typically developing (TD) peers on the Twenty Questions Task (TQT), a measure of verbal problem-solving skills. Although problems with the TQT are typically associated with executive dysfunction, they have also been reported in children who are deaf, suggesting a role for atypical language development. To test the contribution of language history to ASD problem solving, TQT performance was compared in children with high-functioning autism (HFA), children with Asperger syndrome (AS) and TD children. The HFA group used significantly less efficient strategies than both AS and TD children. No group differences were evident on tests of question understanding, planning or verbal fluency. Potential explanations for differences in verbal problem-solving skill are discussed with reference to the development of inner speech and use of visual strategies in ASD. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Benke TA. {{What you seize is what you get: do we yet understand epilepsy in rett syndrome?}}. {Epilepsy Curr};2014 (Sep);14(5):283-285.
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4. Cellot G, Cherubini E. {{Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders}}. {Physiol Rep};2014;2(7)
Neuroligins are postsynaptic adhesion molecules that interacting with presynaptic neurexins ensure the cross-talk between pre- and postsynaptic specializations. Rare mutations in neurexin-neuroligin genes have been linked to autism spectrum disorders (ASDs). One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs. Animals carrying this mutation (NL3(R451C) knock-in mice) exhibit impaired social behaviors, reminiscent of those observed in ASD patients, associated with major alterations in both GABAergic and glutamatergic transmission, which vary among different brain regions and at different developmental stages. Here, pair recordings from parvalbumin- (PV) expressing basket cells and spiny neurons were used to study GABAergic synaptic signaling in layer IV barrel cortex of NL3(R451C) mutant mice. We found that the R451C mutation severely affects the probability of GABA release from PV-expressing basket cells, responsible for controlling via thalamo-cortical inputs the feed-forward inhibition. No changes in excitatory inputs to parvalbumin-positive basket cells or spiny neurons were detected. These data clearly show that primary targets of the NL3 mutation are PV-expressing basket cells, independently of the brain region where they are localized. Changes in the inhibitory gate of layer IV somatosensory cortex may alter sensory processing in ASD patients leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole.
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5. Corbett BA, Qualls LR, Valencia B, Fecteau SM, Swain DM. {{Peer-mediated theatrical engagement for improving reciprocal social interaction in autism spectrum disorder}}. {Front Pediatr};2014;2:110.
The hallmark characteristic of autism spectrum disorder (ASD) is poor reciprocal social communication. Interventions designed to improve this core deficit are critically needed. Social skills interventions such as direct training, peer mediation, and video modeling have contributed to improvements in various social skills in children with ASD. This paper reviews existing social competence interventions available for children with ASD while highlighting hypothesized critical components for advancing, maintaining, and generalizing skills, which include (1) peer mediation, (2) active learning, and (3) implementation in supportive, natural contexts. As a framework for these approaches, this conceptual paper describes SENSE Theatre, a novel intervention that combines trained peers that facilitate the performance-based theatrical treatment delivered in a supportive, community-based environment. A review of previous research shows early feasibility, setting the stage for more rigorous studies to aid in developing a standardized intervention package.
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6. Delfs CH, Frampton SE. {{Practical implications of evaluating the efficiency of listener and tact instruction for children with autism}}. {J Appl Behav Anal};2014 (Oct 24)
Recent literature reviews have highlighted the need to better understand the relation between speaker and listener behavior when teaching learners with autism spectrum disorder (ASD). The current paper outlines the practical implications of evaluating the emergence of tact and listener behavior during instruction for the opposite relation, as presented in the preceding article « Evaluating the Efficiency of Listener and Tact Instruction for Children with Autism. » Modifications of those procedures for clinical use as well as future directions for research in this area are presented.
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7. Hardan AY, Gengoux GW, Berquist KL, Libove RA, Ardel CM, Phillips J, Frazier TW, Minjarez MB. {{A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism}}. {J Child Psychol Psychiatry};2014 (Oct 27)
BACKGROUND: With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD. METHODS: Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov). RESULTS: Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG. CONCLUSIONS: This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms.
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8. Lotta LT, Conrad K, Cory-Slechta D, Schor NF. {{Cerebellar Purkinje cell p75 neurotrophin receptor and autistic behavior}}. {Transl Psychiatry};2014;4:e476.
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9. Oddi D, Subashi E, Middei S, Bellocchio L, Lemaire-Mayo V, Guzman M, Crusio WE, D’Amato FR, Pietropaolo S. {{Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome}}. {Neuropsychopharmacology};2014 (Oct 28)
Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional non-lactating female. At adulthood they were tested for locomotor, social and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, i.e., hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature versus mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of non-pharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.Neuropsychopharmacology accepted article preview online, 28 October 2014. doi:10.1038/npp.2014.291.
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10. Singleton CJ, Ashwin C, Brosnan M. {{Physiological Responses to Social and Nonsocial Stimuli in Neurotypical Adults With High and Low Levels of Autistic Traits: Implications for Understanding Nonsocial Drive in Autism Spectrum Disorders}}. {Autism Res};2014 (Oct 24)
Researchers have suggested that the two primary cognitive features of autism spectrum disorder (ASD), a drive toward nonsocial processing and a reduced drive toward social processing, may be unrelated to each other in the neurotypical (NT) population and may therefore require separate explanations. Drive toward types of processing may be related to physiological arousal to categories of stimuli, such as social (e.g., faces) or nonsocial (e.g., trains). This study investigated how autistic traits in an NT population might relate to differences in physiological responses to nonsocial compared with social stimuli. NT participants were recruited to examine these differences in those with high vs. low degrees of ASD traits. Forty-six participants (21 male, 25 female) completed the Autism Spectrum Quotient (AQ) to measure ASD traits before viewing a series of 24 images while skin conductance response (SCR) was recorded. Images included six nonsocial, six social, six face-like cartoons, and six nonsocial (relating to participants’ personal interests). Analysis revealed that those with a higher AQ had significantly greater SCR arousal to nonsocial stimuli than those with a low AQ, and the higher the AQ, the greater the difference between SCR arousal to nonsocial and social stimuli. This is the first study to identify the relationship between AQ and physiological response to nonsocial stimuli, and a relationship between physiological response to both social and nonsocial stimuli, suggesting that physiological response may underlie the atypical drive toward nonsocial processing seen in ASD, and that at the physiological level at least the social and nonsocial in ASD may be related to one another. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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11. Van de Cruys S, Evers K, Van der Hallen R, Van Eylen L, Boets B, de-Wit L, Wagemans J. {{Precise minds in uncertain worlds: Predictive coding in autism}}. {Psychol Rev};2014 (Oct);121(4):649-675.
There have been numerous attempts to explain the enigma of autism, but existing neurocognitive theories often provide merely a refined description of 1 cluster of symptoms. Here we argue that deficits in executive functioning, theory of mind, and central coherence can all be understood as the consequence of a core deficit in the flexibility with which people with autism spectrum disorder can process violations to their expectations. More formally we argue that the human mind processes information by making and testing predictions and that the errors resulting from violations to these predictions are given a uniform, inflexibly high weight in autism spectrum disorder. The complex, fluctuating nature of regularities in the world and the stochastic and noisy biological system through which people experience it require that, in the real world, people not only learn from their errors but also need to (meta-)learn to sometimes ignore errors. Especially when situations (e.g., social) or stimuli (e.g., faces) become too complex or dynamic, people need to tolerate a certain degree of error in order to develop a more abstract level of representation. Starting from an inability to flexibly process prediction errors, a number of seemingly core deficits become logically secondary symptoms. Moreover, an insistence on sameness or the acting out of stereotyped and repetitive behaviors can be understood as attempts to provide a reassuring sense of predictive success in a world otherwise filled with error. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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12. Weiss JA, Thomson K, Chan L. {{A Systematic Literature Review of Emotion Regulation Measurement in Individuals With Autism Spectrum Disorder}}. {Autism Res};2014 (Oct 24)
Emotion regulation (ER) difficulties are a potential common factor underlying the presentation of multiple emotional and behavioral problems in individuals with Autism Spectrum Disorder (ASD). To provide an overview of how ER has been studied in individuals with ASD, we conducted a systematic review of the past 20 years of ER research in the ASD population, using established keywords from the most comprehensive ER literature review of the typically developing population to date. Out of an initial sampling of 305 studies, 32 were eligible for review. We examined the types of methods (self-report, informant report, naturalistic observation/ behavior coding, physiological, and open-ended) and the ER constructs based on Gross and Thompson’s modal model (situation selection, situation modification, attention deployment, cognitive change, and response modulation). Studies most often assessed ER using one type of method and from a unidimensional perspective. Across the 32 studies, we documented the types of measures used and found that 38% of studies used self-report, 44% included an informant report measure, 31% included at least one naturalistic observation/behavior coding measure, 13% included at least one physiological measure, and 13% included at least one open-ended measure. Only 25% of studies used more than one method of measurement. The findings of the current review provide the field with an in-depth analysis of various ER measures and how each measure taps into an ER framework. Future research can use this model to examine ER in a multicomponent way and through multiple methods. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Wiggins LD, Reynolds A, Rice CE, Moody EJ, Bernal P, Blaskey L, Rosenberg SA, Lee LC, Levy SE. {{Using Standardized Diagnostic Instruments to Classify Children with Autism in the Study to Explore Early Development}}. {J Autism Dev Disord};2014 (Oct 28)
The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome.
