Pubmed du 10/04/18

mardi 10 avril 2018

1. Aspiranti KB, Larwin KH, Schade BP. iPads/tablets and students with autism : a meta-analysis of academic effects. Assistive technology : the official journal of RESNA. 2018.

Since the introduction of iPads in 2010, educators have been working to effectively incorporate this technology as a supplement to curriculum and a tool to increase student engagement and student achievement. The current investigation examines the effectiveness of iPad applications in supporting the instruction of students identified on the autism spectrum. Specifically, this investigation provides a meta-analysis of available research that examines the use of iPad technology and its impact on learning outcomes for students with autism. Four studies were found that provided results for groups of students. The findings of this research are based on 12 effect-size measures, representing a synthesized sample size of 99 participants. The results suggest that the use of iPad technology can have a positive, significant effect on student learning outcomes. The moderators of these positive outcomes are presented and discussed.

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2. Banerjee A, Ifrim MF, Valdez AN, Raj N, Bassell GJ. Aberrant RNA Translation in Fragile X Syndrome : From FMRP Mechanisms to Emerging Therapeutic Strategies. Brain Res. 2018.

Research in the past decades has unfolded the multifaceted role of Fragile X mental retardation protein (FMRP) and how its absence contributes to the pathophysiology of Fragile X syndrome (FXS). Excess signaling through group 1 metabotropic glutamate receptors is commonly observed in mouse models of FXS, which in part is attributed to dysregulated translation and downstream signaling. Considering the wide spectrum of cellular and physiologic functions that loss of FMRP can affect in general, it may be advantageous to pursue disease mechanism based treatments that directly target translational components or signaling factors that regulate protein synthesis. Various FMRP targets upstream and downstream of the translational machinery are therefore being investigated to further our understanding of the molecular mechanism of RNA and protein synthesis dysregulation in FXS as well as test their potential role as therapeutic interventions to alleviate FXS associated symptoms. In this review, we will broadly discuss recent advancements made towards understanding the role of FMRP in translation regulation, new pre-clinical animal models with FMRP targets located at different levels of the translational and signal transduction pathways for therapeutic intervention as well as future use of stem cells to model FXS associated phenotypes.

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3. Besseling R, Lamerichs R, Michels B, Heunis S, de Louw A, Tijhuis A, Bergmans J, Aldenkamp B. Functional network abnormalities consistent with behavioral profile in Autism Spectrum Disorder. Psychiatry Res. 2018.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which the severity of symptoms varies over subjects. The iCAPs model (innovation-driven co-activation patterns) is a recently developed spatio-temporal model to describe fMRI data. In this study, the iCAPs model was employed to find functional imaging biomarkers for ASD in resting-state fMRI data. MRI data from 125 ASD patients and 243 healthy controls was selected from the online ABIDE data repository. Following standard fMRI preprocessing steps, the iCAP patterns were fitted to the data to obtain network time series. Furthermore, specific combinations of iCAPs were mapped to behavioral domain time series. To quantify to which extent the time series contribute to the fMRI dynamics, their (temporal) standard deviation was calculated and compared between patients and controls. Abnormalities were found in networks involving subcortical and limbic areas and default mode network regions. When mapping the network dynamics to behavioral domain time series, abnormalities were found in emotional and visual behavioral subdomains, and within the ASD spectrum were more pronounced in subjects with autism compared to Asperger’s syndrome. Also a trend towards impairment in networks facilitating social cognition was found. The functional imaging abnormalities are consistent with the behavioral impairments typical for ASD.

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4. Celikkol C, Bilgic A. Excessive Masturbation Successfully Treated with Fluoxetine in an Adolescent with Autism Spectrum Disorder and Coexisting Depression. J Child Adolesc Psychopharmacol. 2018.

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5. Goris J, Braem S, Nijhof AD, Rigoni D, Deschrijver E, Van de Cruys S, Wiersema JR, Brass M. Sensory Prediction Errors Are Less Modulated by Global Context in Autism Spectrum Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018.

BACKGROUND : Recent predictive coding accounts of autism spectrum disorder (ASD) suggest that a key deficit in ASD concerns the inflexibility in modulating local prediction errors as a function of global top-down expectations. As a direct test of this central hypothesis, we used electroencephalography to investigate whether local prediction error processing was less modulated by global context (i.e., global stimulus frequency) in ASD. METHODS : A group of 18 adults with ASD was compared with a group of 24 typically developed adults on a well-validated hierarchical auditory oddball task in which participants listened to short sequences of either five identical sounds (local standard) or four identical sounds and a fifth deviant sound (local deviant). The latter condition is known to generate the mismatch negativity (MMN) component, believed to reflect early sensory prediction error processing. Crucially, previous studies have shown that in blocks with a higher frequency of local deviant sequences, top-down expectations seem to attenuate the MMN. We predicted that this modulation by global context would be less pronounced in the ASD group. RESULTS : Both groups showed an MMN that was modulated by global context. However, this effect was smaller in the ASD group as compared with the typically developed group. In contrast, the P3b, as an electroencephalographic marker of conscious expectation processes, did not differ across groups. CONCLUSIONS : Our results demonstrate that people with ASD are less flexible in modulating their local predictions (reflected in MMN), thereby confirming the central hypothesis of contemporary predictive coding accounts of ASD.

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6. Jia F, Shan L, Wang B, Li H, Feng J, Xu Z, Saad K. Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children : Three cases report. Nutr Neurosci. 2018 : 1-4.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

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7. Lin MA, Cannon SC, Papazian DM. Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening. Proceedings of the National Academy of Sciences of the United States of America. 2018 ; 115(15) : E3559-e68.

A de novo mutation in the KCND2 gene, which encodes the Kv4.2 K(+) channel, was identified in twin boys with intractable, infant-onset epilepsy and autism. Kv4.2 channels undergo closed-state inactivation (CSI), a mechanism by which channels inactivate without opening during subthreshold depolarizations. CSI dynamically modulates neuronal excitability and action potential back propagation in response to excitatory synaptic input, controlling Ca(2+) influx into dendrites and regulating spike timing-dependent plasticity. Here, we show that the V404M mutation specifically affects the mechanism of CSI, enhancing the inactivation of channels that have not opened while dramatically impairing the inactivation of channels that have opened. The mutation gives rise to these opposing effects by increasing the stability of the inactivated state and in parallel, profoundly slowing the closure of open channels, which according to our data, is required for CSI. The larger volume of methionine compared with valine is a major factor underlying altered inactivation gating. Our results suggest that V404M increases the strength of the physical interaction between the pore gate and the voltage sensor regardless of whether the gate is open or closed. Furthermore, in contrast to previous proposals, our data strongly suggest that physical coupling between the voltage sensor and the pore gate is maintained in the inactivated state. The state-dependent effects of V404M on CSI are expected to disturb the regulation of neuronal excitability and the induction of spike timing-dependent plasticity. Our results strongly support a role for altered CSI gating in the etiology of epilepsy and autism in the affected twins.

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8. Meng FC, Xu XJ, Song TJ, Shou XJ, Wang XL, Han SP, Han JS, Zhang R. Development of an Autism Subtyping Questionnaire Based on Social Behaviors. Neurosci Bull. 2018.

Autism spectrum disorder can be differentiated into three subtypes (aloof, passive, and active-but-odd) based on social behaviors according to the Wing Subgroups Questionnaire (WSQ). However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically-developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire (BASQ). Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.

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9. Miniscalco C, Fernell E, Thompson L, Sandberg E, Kadesjo B, Gillberg C. Development problems were common five years after positive screening for language disorders and, or, autism at 2.5 years of age. Acta paediatrica (Oslo, Norway : 1992). 2018.

AIM : This study identified whether children who had screened positive for either developmental language disorder (DLD) or autism spectrum disorder (ASD) at the age of 2.5 years had neurodevelopmental assessments five years later. METHODS : Our study cohort were 288 children born from 1 July 2008-20 June 2009 who screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were referred to, and assessed, at the Paediatric Speech and Language Pathology clinic (n=176) or the Child Neuropsychiatry Clinic (n=61) at the Queen Silvia Children’s Hospital, Gothenburg, Sweden. Clinical registers covering all relevant outpatient clinics were reviewed five years later with regard to established diagnoses. RESULTS : When the 237 were followed up five years later, 96 (40%) had established neurodevelopmental disorders or problems, often beyond DLD and ASD. Co-existing problems were common in this cohort and multidisciplinary assessments were indicated. The other 60% did not appear in subsequent clinic records. It is likely that this 40% was a minimum rate and that more children will be referred for developmental problems later. CONCLUSION : Five years after they had been screened positive for DLD and, or autism at 2.5 years, 40% of our cohort had remaining or other developmental problems. This article is protected by copyright. All rights reserved.

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10. Reilly M, Fogler J, Bridgemohan C, Wiley M, Weitzman C, Augustyn M. Helping a Child with Autism Spectrum Disorder Cope with Divorce. J Dev Behav Pediatr. 2018.

CASE : Aaron is an 11-year-old boy with autism spectrum disorder (ASD), with cognitive and language skills in the above-average range, whose parents have recently separated. Aaron’s mother initiated the separation when she learned that Aaron’s father had maintained a relationship with a woman with whom he has a 10-year-old daughter. When Aaron’s mother discovered this relationship, she demanded that Aaron’s father leave their home.Aaron’s father has moved in with his long-term girlfriend and keeps in contact with Aaron by calling once a day. Neither Aaron’s father nor mother has discussed the reason for their separation with Aaron. So far, they have explained their separation by telling Aaron that they are "taking a break."Aaron’s mother has been deeply hurt by Aaron’s father’s infidelity and does not want to reconcile with him. Aaron’s father recognizes this but would like to continue to have a close relationship with his son. He would also like Aaron to get to know his half-sister.Aaron’s mother seeks guidance regarding how to talk to Aaron about the separation and his father’s second family. Given Aaron’s diagnosis of ASD, she is particularly concerned about his ability to cope with this unexpected change in circumstances. What is your advice ?

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11. Rigby SN, Stoesz BM, Jakobson LS. Empathy and face processing in adults with and without autism spectrum disorder. Autism Res. 2018.

Many factors contribute to social difficulties in individuals with autism spectrum disorder (ASD). The goal of the present work was to determine whether atypicalities in how individuals with ASD process static, socially engaging faces persist when nonrigid facial motion cues are present. We also sought to explore the relationships between various face processing abilities and individual differences in autism symptom severity and traits such as empathy. Participants included 16 adults with ASD without intellectual impairment and 16 sex- and age-matched controls. Mean Verbal IQ was comparable across groups [t(30) = 0.70, P = 0.49]. The two groups responded similarly to many of the experimental manipulations ; however, relative to controls, participants with ASD responded more slowly to dynamic expressive faces, even when no judgment was required ; were less accurate at identity matching with static and dynamic faces ; and needed more time to make identity and expression judgments [F(1, 30) >/= 6.37, P /= 0.175 in all cases], particularly when the faces were moving [F(1, 30) = 3.40, P = 0.072, etap(2) = 0.104]. In the full sample, as social autistic traits increased and empathic skills declined, participants needed more time to judge static identity, and static or dynamic expressions [0.43 < |rs | < 0.56]. The results suggest that adults with ASD show general impairments in face and motion processing and support the view that an examination of individual variation in particular personality traits and abilities is important for advancing our understanding of face perception. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Our findings suggest that people with ASD have problems processing expressive faces, especially when seen in motion. It is important to learn who is most at risk for face processing problems, given that in the general population such problems appear to be linked to impaired social skills and empathy. By studying relationships between different abilities and traits, we may be able to find better ways to diagnose and support all people on the autism spectrum.

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12. Romero V, Fitzpatrick P, Roulier S, Duncan A, Richardson MJ, Schmidt RC. Correction : Evidence of embodied social competence during conversation in high functioning children with autism spectrum disorder. PLoS One. 2018 ; 13(4) : e0195888.

[This corrects the article DOI : 10.1371/journal.pone.0193906.].

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13. Wang Q, Campbell DJ, Macari SL, Chawarska K, Shic F. Operationalizing atypical gaze in toddlers with autism spectrum disorders : a cohesion-based approach. Mol Autism. 2018 ; 9 : 25.

Background : Multiple eye-tracking studies have highlighted the "atypical" nature of social attention in autism. However, it is unclear how "atypical" or "typical" should be quantified. Methods : We developed a method for identifying moments when members of a group looked at similar places (High-Cohesion Time Frames ; HCTFs). We defined typicality as the proximity of gaze points to typically developing (TD) gaze points during TD HCTFs. Comparing toddlers with ASD (n = 112) to developmentally delayed (DD, n = 36) and TD (n = 163) toddlers during a video with Dyadic Bid, Sandwich-Making, Joint Attention, and Animated Toys conditions, we examined (a) individual typicality scores, (b) the relationship between typicality and symptom severity, and (c) HCTF distributions associated with each diagnostic group. Results : The ASD group had lower gaze typicality scores compared to the TD and DD groups in the Dyadic Bid and Sandwich-Making conditions but not during Animated Toys. The DD and TD groups did not differ in any condition. Correlational analyses indicated that higher typicality scores were associated with increased looking at pre-planned locations of the scene indexed by each experimental condition. In the ASD group, lower gaze typicality was associated with more severe autism symptoms. Examining ASD HCTFs, the gaze of toddlers with ASD was least cohesive during Dyadic Bid and most cohesive during Animated Toys. Conclusion : In contrast to non-ASD groups, toddlers with ASD show high cohesion during salient nonsocial events, suggesting that consistency in looking strategies may depend more on perceptual features. These findings are consequential for understanding individual differences in visual attention in ASD and for the design of more sensitive biomarker tasks for stratification, between-group differentiation, and measuring response to treatment.

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