Pubmed du 08/08/19

jeudi 8 août 2019

1. Baum RA. Learning To Play and Playing To Learn : Enhancing Interactions in Young Children With ASD. Pediatrics ;2019 (Aug 6)

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2. Cordero C, Schieve LA, Croen LA, Engel SM, Maria Siega-Riz A, Herring AH, Vladutiu CJ, Seashore CJ, Daniels JL. Neonatal jaundice in association with autism spectrum disorder and developmental disorder. J Perinatol ;2019 (Aug 6)

OBJECTIVE : To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). STUDY DESIGN : We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2-5 years into : ASD (n = 636), DD (n = 777), or controls (POP ; n = 926). Neonatal jaundice (n = 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). RESULTS : Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35-37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not >/=38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. CONCLUSIONS : Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted.

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3. Dimitropoulos A, Zyga O, Russ SW. Early Social Cognitive Ability in Preschoolers with Prader-Willi Syndrome and Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Aug 6)

Children with Prader-Willi syndrome (PWS) and autism spectrum disorder (ASD) present with challenges in social cognitive ability, Research comparing PWS to ASD is important given the implication of 15q11-q13 region in the biology of autism. However, recent findings question the accuracy of relying solely on parent report in behavioral characterization. Thus, this study examined social cognition in an observable pretend play task and by parent report in 50 preschool children (ages 3-5) with PWS, by subtype, compared to ASD. Behaviorally, the paternal deletion subtype expressed overall higher functioning, whereas the maternal uniparental disomy subtype performed more similarly to the ASD group. Results are the first to show deficits in social cognitive ability early in development. The severity and differences in deficits between PWS subtypes are important in informing early intervention efforts.

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4. DiPietro J, Kelemen A, Liang Y, Sik-Lanyi C. Computer- and Robot-Assisted Therapies to Aid Social and Intellectual Functioning of Children with Autism Spectrum Disorder. Medicina (Kaunas) ;2019 (Aug 5) ;55(8)

BACKGROUND AND OBJECTIVES : Children with autism spectrum disorder (ASD) experience challenges with social interactions, a core feature of the disorder. Social skills therapy has been shown to be helpful. Over the past several years, computer-assisted and robot-assisted therapies have been infiltrating the social skills teaching environment. Rapid progress in the field of technology, especially in the robotics area, offers tremendous possibilities for innovation and treatment or even education for individuals with ASD. This paper’s purpose is to drive awareness of these innovative interventions in order to support the social lives of children with ASD. The aims of the paper are identifying (1) the types of Information Technology platforms that are being evaluated in computer and robot-assisted therapies for children with ASD ; (2) the various disciplines or professions studying and utilizing these computer and robot-assisted social skill therapies ; (3) the outcomes being evaluated in each trial ; and (4) if results demonstrate benefits to children with autism. MATERIALS AND METHODS : PubMed, CINAHL, Science Direct, and Web of Science databases were searched for clinical trials published over the past five years. Search terms incorporated the subject intersection of autism, and computer or robot-assisted therapy. Results were mined for pediatric populations only and study designs establishing controlled comparisons. RESULTS : Eighteen unique international studies were identified that utilize robot interventions (11 studies) and serious computer game interventions (seven studies). Most demonstrated promising results in improving outcomes for children with ASD. Study implications reveal a rapidly evolving assistive technology for ASD social skills therapy. CONCLUSIONS : These interventions show considerable promise, but more effectiveness and cost effectiveness research of high quality should be carried out with larger numbers of children. Also, further studies are necessary to evaluate these technologies’ effectiveness amongst adults with ASD and within unique subsets of the higher functioning autism population.

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5. Estes A, St John T, Dager SR. What to Tell a Parent Who Worries a Young Child Has Autism. JAMA Psychiatry ;2019 (Aug 7)

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6. Gengoux GW, Abrams DA, Schuck R, Millan ME, Libove R, Ardel CM, Phillips JM, Fox M, Frazier TW, Hardan AY. A Pivotal Response Treatment Package for Children With Autism Spectrum Disorder : An RCT. Pediatrics ;2019 (Aug 6)

OBJECTIVES : Our aim was to conduct a randomized controlled trial to evaluate a pivotal response treatment package (PRT-P) consisting of parent training and clinician-delivered in-home intervention on the communication skills of children with autism spectrum disorder. METHODS : Forty-eight children with autism spectrum disorder and significant language delay between 2 and 5 years old were randomly assigned to PRT-P (n = 24) or the delayed treatment group (n = 24) for 24 weeks. The effect of treatment on child communication skills was assessed via behavioral coding of parent-child interactions, standardized parent-report measures, and blinded clinician ratings. RESULTS : Analysis of child utterances during the structured laboratory observation revealed that, compared with the delayed treatment group, children in PRT-P demonstrated greater improvement in frequency of functional utterances (F1,41 = 6.07 ; P = .026 ; d = 0.61). The majority of parents in the PRT-P group (91%) were able to implement pivotal response treatment (PRT) with fidelity within 24 weeks. Children receiving PRT-P also demonstrated greater improvement on the Brief Observation of Social Communication Change, on the Clinical Global Impressions Improvement subscale, and in number of words used on a parent-report questionnaire. CONCLUSIONS : This is the first 24-week randomized controlled trial in which community treatment is compared with the combination of parent training and clinician-delivered PRT. PRT-P was effective for improving child social communication skills and for teaching parents to implement PRT. Additional research will be needed to understand the optimal combination of treatment settings, intensity, and duration, and to identify child and parent characteristics associated with treatment response.

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7. Guo D, Peng Y, Wang L, Sun X, Wang X, Liang C, Yang X, Li S, Xu J, Ye WC, Jiang B, Shi L. Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. Mol Psychiatry ;2019 (Aug 6)

Genetic studies of autism spectrum disorder (ASD) have revealed multigene variations that converge on synaptic dysfunction. DOCK4, a gene at 7q31.1 that encodes the Rac1 guanine nucleotide exchange factor Dock4, has been identified as a risk gene for ASD and other neuropsychiatric disorders. However, whether and how Dock4 disruption leads to ASD features through a synaptic mechanism remain unexplored. We generated and characterized a line of Dock4 knockout (KO) mice, which intriguingly displayed a series of ASD-like behaviors, including impaired social novelty preference, abnormal isolation-induced pup vocalizations, elevated anxiety, and perturbed object and spatial learning. Mice with conditional deletion of Dock4 in hippocampal CA1 recapitulated social preference deficit in KO mice. Examination in CA1 pyramidal neurons revealed that excitatory synaptic transmission was drastically attenuated in KO mice, accompanied by decreased spine density and synaptic content of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)- and NMDA (N-methyl-D-aspartate)-type glutamate receptors. Moreover, Dock4 deficiency markedly reduced Rac1 activity in the hippocampus, which resulted in downregulation of global protein synthesis and diminished expression of AMPA and NMDA receptor subunits. Notably, Rac1 replenishment in the hippocampal CA1 of Dock4 KO mice restored excitatory synaptic transmission and corrected impaired social deficits in these mice, and pharmacological activation of NMDA receptors also restored social novelty preference in Dock4 KO mice. Together, our findings uncover a previously unrecognized Dock4-Rac1-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and social behavior.

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8. Kahanovitch U, Patterson KC, Hernandez R, Olsen ML. Glial Dysfunction in MeCP2 Deficiency Models : Implications for Rett Syndrome. Int J Mol Sci ;2019 (Aug 5) ;20(15)

Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder typically affecting females, resulting in a range of symptoms including autistic features, intellectual impairment, motor deterioration, and autonomic abnormalities. RTT is primarily caused by the genetic mutation of the Mecp2 gene. Initially considered a neuronal disease, recent research shows that glial dysfunction contributes to the RTT disease phenotype. In the following manuscript, we review the evidence regarding glial dysfunction and its effects on disease etiology.

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9. Kokol P, Vosner HB, Zavrsnik J, Vermeulen J, Shohieb S, Peinemann F. Serious game-based intervention for children with developmental disabilities. Curr Pediatr Rev ;2019 (Aug 8)

BACKGROUND : Children with developmental disabilities may need support with motor skills such as balance improvement, cognitive skills such as vocabulary learning, or social skills such as adequate interpretation of emotional expressions. Digital interactive games could support the standard treatments. We aimed to review clinical studies which investigated the application of serious games in children with developmental disabilities. METHOD : We searched MEDLINE and Scopus on 05 May 2019 limited to English language. We included people between two and 24 years of age who were affected by neurodevelopmental disorders who received digital serious game-based medical interventions such as any computer-based or video-based games. We considered any study design reporting primary data. We used title, abstract, and full-text of journal articles to build diagnostic groups, and we described some selected specific game applications. RESULTS : The majority of the 145 relevant studies reported on autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental coordination disorder (DCD), and disabilities affecting intellectual abilities (DAIA). 30 of the 145 studies reported a randomized design. We detailed six specific applications aimed at improving abilities in children with ASD, ADHD, cerebral palsy, and Down syndrome. We visualized the diagnostic groups by bibliographic mapping, and we limited the text to the title and abstract of journal articles. CONCLUSION : We identified promising results regarding anxiety reduction, stress regulation, emotion recognition, and rehabilitation. Currently, there appears to be a lack of clinical evidence that children with neurodevelopmental disorders can benefit from the application of serious games.

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10. Orefice LL, Mosko JR, Morency DT, Wells MF, Tasnim A, Mozeika SM, Ye M, Chirila AM, Emanuel AJ, Rankin G, Fame RM, Lehtinen MK, Feng G, Ginty DD. Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models. Cell ;2019 (Aug 8) ;178(4):867-886.e824.

Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors. Moreover, acute treatment with a peripherally restricted GABAA receptor agonist that acts directly on mechanosensory neurons reduced tactile over-reactivity in six distinct ASD models. Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, some brain abnormalities, anxiety-like behaviors, and some social impairments but not memory impairments, motor deficits, or overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.

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11. Ruzzo EK, Perez-Cano L, Jung JY, Wang LK, Kashef-Haghighi D, Hartl C, Singh C, Xu J, Hoekstra JN, Leventhal O, Leppa VM, Gandal MJ, Paskov K, Stockham N, Polioudakis D, Lowe JK, Prober DA, Geschwind DH, Wall DP. Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Cell ;2019 (Aug 8) ;178(4):850-866.e826.

We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extension of previous findings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.

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12. Vukicevic S, Dordevic M, Glumbic N, Bogdanovic Z, Duric Jovicic M. A Demonstration Project for the Utility of Kinect-Based Educational Games to Benefit Motor Skills of Children with ASD. Percept Mot Skills ;2019 (Aug 7):31512519867521.

Motor disorders often accompany autism spectrum disorder (ASD), although they are not included in its diagnostic criteria. Slower motor development is evident in early childhood in this population, making early motor skills intervention advisable. As educational games and modern technology can represent new forms of treatment, this study evaluated four Kinect-based visuo-motor games called Fruits that were specially designed for this research. We sought to test whether children with ASD would show behavior changes during their game play and whether any effects would generalize to another game called Rackets. The study included 10 elementary school children with ASD, aged 9-13 years, who were divided into (a) an experimental group (n = 5) who, in addition to standard treatment, played Fruits once a week for a 5-week period and Rackets both before and after the 5-week period and (b) a control group (n = 5) who received only standard treatment during this period and also played Rackets before and after it. We found significant improvements in gross motor skills and successful generalization of acquired skills among children in the experimental group relative to the control group. The experimental group also showed an increase in positive emotions and a decrease in loss of attention while playing the games. These preliminary findings indicate a motor skill benefit for children with ASD who play Kinect-based educational games, but further research is needed to replicate and expand these findings with larger participant samples.

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13. Yang YC, Lu L, Jeng SF, Tsao PN, Cheong PL, Li YJ, Wang SY, Huang HC, Wu YT. Multidimensional Developments and Free-Play Movement Tracking in 30- to 36-Month-Old Toddlers With Autism Spectrum Disorder Who Were Full Term. Phys Ther ;2019 (Aug 8)

BACKGROUND : Few studies have investigated multidimensional developments and free-play movement performance in toddlers with an early diagnosis of autism spectrum disorder (ASD). OBJECTIVE : This study compared cognitive, motor, and behavioral developments and free-play movement performance in toddlers with ASD who were full term (FT-ASD), toddlers who were full term and are typically developing (FT-TD), and toddlers who were born preterm and had a very low birth weight (VLBW-PT). DESIGN : This was a prospective cross-sectional study. METHODS : Forty-five 30- to 36-month-old age-matched toddlers were recruited and divided into FT-ASD, FT-TD, and VLBW-PT groups. Their developments were examined using the Mullen Scales of Early Learning ; the Peabody Developmental Motor Scales, Second Edition ; the Child Behavior Checklist for Ages 1.5-5 ; and the Repetitive Behavior Scale-Revised. In addition, the toddlers’ free-play movements were tracked in laboratory settings using an automatic movement tracking system. RESULTS : Toddlers with FT-ASD exhibited lower cognitive and motor scores and a higher degree of behavioral problems compared with toddlers with FT-TD or VLBW-PT. Furthermore, the movement tracking data in a free-play setting revealed toddlers with FT-ASD performed a higher degree of turning velocity, a higher moving time, and a higher frequency of moving toward the peripheral region compared with toddlers with FT-TD or VLBW-PT. Moreover, several motor developmental and movement tracking indicators were found to correlate with behavioral problems and cognitive scores in toddlers with FT-ASD. LIMITATIONS : The study results may have been affected by the small sample size, the cross-sectional design, and tracking only the whole body without subtle movements or segmental motions. CONCLUSIONS : The findings suggest varied aspects of co-occurring developmental conditions and movement-based problems in toddlers with FT-ASD. Using standardized and sensitive measures for the early assessment of perceptuo-motor impairments is necessary for timely early intervention for such toddlers.

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14. Zhang B, Zhou Z, Zhou Y, Zhang T, Ma Y, Niu Y, Ji W, Chen Y. Social-valence-related increased attention in rett syndrome cynomolgus monkeys : An eye-tracking study. Autism Res ;2019 (Aug 7)

The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00 : 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome.

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15. Zhou HY, Yang HX, Gong JB, Cheung EFC, Gooding DC, Park S, Chan RCK. Revisiting the overlap between autistic and schizotypal traits in the non-clinical population using meta-analysis and network analysis. Schizophr Res ;2019 (Aug 3)

The present study aimed to explore the relationship between autistic and schizotypal traits in the non-clinical population. We first conducted a meta-analysis to quantify the correlation between self-reported autistic traits and the three dimensions of schizotypal traits (positive, negative and disorganization). The strongest correlation was found between autistic traits and negative schizotypal traits (r=0.536, 95% CI [0.481, 0.586]), followed by the disorganization (r=0.355, 95% CI [0.304, 0.404]) and positive (r=0.256, 95% CI [0.208, 0.302]) dimensions. To visualize the partial correlations between dimensional behavioural traits, we constructed a network model based on a large sample of college students (N=2469). Negative schizotypal traits were strongly correlated with autistic social/communicative deficits, whereas positive schizotypal traits were inversely correlated with autistic-like traits, lending support to the psychosis-autism diametrical model. Disentangling the overlapping and diametrical structure of autism and schizophrenia may help to elucidate the aetiology of these two neurodevelopmental disorders.

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