Pubmed du 09/07/19

mardi 9 juillet 2019

1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alanazi AZ, Alsanea S, As Sobeai HM, Almutairi MM, Mahmood HM, Attia SM. The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T(+) Itpr3(tf)/J mouse model of autism. Brain Res Bull ;2019 (Jul 9) ;152:27-34.

Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. BTBR T(+) Itpr3(tf)/J (BTBR) mice serve as an accepted model to evaluate autistic-like behaviors as they display core behavioral symptoms displayed in autism. Previous findings showed that S3I-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S3I-201 treatment has therapeutic effects on autism-like behaviors, and Th1/Th17 and regulatory T cells in BTBR mice. The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4(+)CD25(+) and CD4(+)CD69(+)), chemokine receptors (CD4(+)CCR6(+), CD4(+)CCR7(+), CD4(+)CXCR4(+), and CD4(+)CXCR5(+)), and proinflammatory cytokines (CD4(+)IL-6(+) and CD4(+)TNF-alpha(+)) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1beta, IL-6, and TNF-alpha were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-alpha producing CD4(+) T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.

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2. Asgarihafshejani A, Nashmi R, Delaney KR. Cell-Genotype Specific Effects of Mecp2 Mutation on Spontaneous and Nicotinic Acetylcholine Receptor-Evoked Currents in Medial Prefrontal Cortical Pyramidal Neurons in Female Rett Model Mice. Neuroscience ;2019 (Jul 9)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene. Random X-inactivation produces a mosaic of mutant (MT) and wild-type (WT) neurons in female Mecp2+/- (het) mice. Many RTT symptoms are alleviated by increasing activity in medial prefrontal cortex (mPFC) in RTT model mice (Howell et al., 2017). Using a GFP-MeCP2 fusion protein to distinguish WT from MT pyramidal neurons in mPFC we found cell autonomous (cell genotype specific) and non-autonomous effects of MeCP2 deficiency on spontaneous excitatory/inhibitory balance, nicotinic acetylcholine receptor (nAChR) currents and evoked activity. MT Layer 5 and 6 (L5, L6) neurons of male nulls, and MT L6 of het mice had reduced spontaneous excitatory synaptic input compared to WT in wild-type male (WTm), female (WTf) and het mice. Inhibitory synaptic charge in MT L6 equaled WT in 2-4-month hets. At 6-7months inhibitory charge in WT in het slices was increased compared to both MT in het and WT in WTf ; however, in hets the excitatory/inhibitory charge ratio was still greater in WT compared to MT. nAChR currents were reduced in L6 of nulls and MT L6 in het slices compared to WT neurons of het, WTm and WTf. At 2-4months, ACh perfusion increased frequency of inhibitory currents to L6 neurons equally in all genotypes but increased excitatory inputs to MT and WT in hets less than WT in WTfs. Unexpectedly ACh perfusion evoked greater sustained IPSC and EPSC input to L5 neurons of nulls compared to WTm.

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3. Cheung CC, Rong Y, Chen F, Chen S, Leung MT, Tang TPY, Peng G. Comprehension of literal statements and similes in Cantonese-speaking children with and without autism spectrum disorders. Clin Linguist Phon ;2019 (Jul 9):1-15.

While it has been proposed, following relevance theory, that similes can be understood at a purely literal level on a par with literal statements, it remains unclear whether children with high-functioning autism spectrum disorders (HFASD) perform similarly to typically developing (TD) children in comprehending literal statements and similes. The present study investigated comprehension of literal statements and similes in Cantonese-speaking children with HFASD and TD children matched on both chronological age and verbal mental age. An utterance-picture matching task was devised to assess their comprehension of literal statements and similes in Cantonese. Overall results showed that Cantonese-speaking children with HFASD performed worse than TD children in comprehending literal statements and similes, and both groups showed more difficulty in comprehending similes than literal statements. After the effects of chronological age and verbal mental age were controlled for, no group difference was found between children with HFASD and TD children in comprehending literal statements, whereas the group difference in simile comprehension still existed, suggesting that children with HFASD showed deficits in comprehending similes relative to TD children. These findings challenge the proposal that similes can be understood at a purely literal level on a par with literal statements. Future studies should investigate the role of different aspects of language ability and different levels of theory-of-mind skills in comprehension of similes and metaphors in children with HFASD.

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4. Eklof E, Martensson GE, Aden U, Padilla N. Reduced structural brain asymmetry during neonatal life is potentially related to autism spectrum disorders in children born extremely preterm. Autism Res ;2019 (Jul 9)

Disruption of the normal patterns of structural brain asymmetry, and in language-related areas, has been reported in individuals with autism spectrum disorder (ASD). We tested the hypothesis that 16 children born extremely preterm (EPT), and diagnosed with ASD at 6.5 years of age (EPT-ASD), would have different patterns of brain structural asymmetry, particularly in language-related areas, to 21 EPT children without ASD and 15 term-born children. They all underwent neonatal magnetic resonance imaging scans at 40 weeks of gestation. ASD diagnoses and the Weschler Intelligence Scale for Children-Fourth Edition, were performed in the EPT children, but not in the term group. Asymmetry indices (AIs) were assessed at three levels : global (hemispheres), lobar (brain lobes), and modular (primary sensorimotor, unimodal, and higher-order association areas). AIs were also assessed in language-related regions and correlational analyses were performed between these AIs and verbal scores. The EPT-ASD group showed reduced structural asymmetry at the modular level, mainly involving the higher-order association cortices and the language-related areas. Predominant positive correlations between language functioning and leftward AIs in the inferior frontal gyrus (opercular) and supplementary cortices, and rightward asymmetry in the angular and supramarginal gyri, were identified in the EPT-ASD group. The overall results suggest that reduced brain structural asymmetry identified during the neonatal period would be a risk factor for the development of ASD in EPT infants. This finding could identify EPT children at risk at an early stage, so that tailored interventions could be used to optimize their functions and quality of life. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Babies born before the expected date (preterm) are more likely to develop autism, due to abnormal brain development. Compared with children without autism, preterm children with autism did not display the important physical differences between the two sides of their brain that are needed for normal functioning. As this alteration was found just after birth, this information could be used to identify children who are likely to develop autism, so that they can get medical support at an earlier age.

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5. Ess KC, Franz DN. Everolimus for cognition/autism in children with tuberous sclerosis complex : Definitive outcomes deferred. Neurology ;2019 (Jul 9) ;93(2):51-52.

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6. Flippin M, Hahs-Vaughn DL. Parent couples’ participation in speech-language therapy for school-age children with autism spectrum disorder in the United States. Autism ;2019 (Jul 9):1362361319862113.

This study examined parent couples’ participation in and satisfaction with speech-language therapy for school-age children with autism spectrum disorder in the United States. Responses from 40 father-mother couples (n = 80 parents) were examined across therapy components (i.e. parent-therapist communication, assessment, planning, and intervention). Descriptive frequencies, chi-square tests, intraclass correlations, and dyadic multilevel modeling were used to examine participation across fathers and mothers and within parent couples. Compared to mothers, fathers communicated less with therapists and participated less in assessment and planning. Fathers also had lower satisfaction than mothers with parent-therapist communication and planning. Although few parents participated in school-based therapy sessions, 40% of fathers and 50% of mothers participated in homework. However, few parents received homework support from therapists. Results are discussed in terms of clinical implications for interventionists to more effectively engage both fathers and mothers in family-centered speech-language therapy for school-aged children with autism spectrum disorder.

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7. Jensen AC, Orsmond GI. The Sisters’ Advantage ? Broader Autism Phenotype Characteristics and Young Adults’ Sibling Support. J Autism Dev Disord ;2019 (Jul 9)

Siblings often oversee the well-being of an adult with autism spectrum disorder (ASD). The current study contributes to the literature by examining correlates of support provided to siblings in young adulthood in the context of the broader autism phenotype (BAP). Young adults (n = 866 ; Mage = 25.43, SD = 2.54 ; 55% female) reported on support provided to and the BAP characteristics of 1198 different siblings (Mage = 28.56, SD = 8.87 ; 50% female). Findings showed that young adults provided more emotional and practical support to sisters that they perceived to be higher in BAP characteristics. These findings suggest that sisters who have characteristics associated with ASD may be at an advantage in receiving support.

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8. Nowell SW, Watson LR, Boyd B, Klinger LG. Efficacy Study of a Social Communication and Self-Regulation Intervention for School-Age Children With Autism Spectrum Disorder : A Randomized Controlled Trial. Lang Speech Hear Serv Sch ;2019 (Jul 12) ;50(3):416-433.

Purpose This study aimed to examine the initial efficacy of a parent-assisted blended intervention combining components of Structured TEACCHing and Social Thinking, designed to increase social communication and self-regulation concept knowledge in 1st and 2nd graders ( n = 17) diagnosed with autism spectrum disorder (ASD) and their parents. Method A randomized delayed treatment control group design with pre- and postintervention assessments of both parents and children was implemented within a community practice setting. Two follow-up assessments at 3 and 6 months postintervention were also completed. Results Overall, results indicate that the intervention is efficacious in teaching social communication and self-regulation concept knowledge to children with ASD and their parents. Both parents and children demonstrated an increase in social communication and self-regulation knowledge after participating in the Growing, Learning, and Living With Autism Group as compared to a delayed treatment control group. The effects of the intervention did not extend to parent-child interactions coded from video recordings. Child treatment effects were maintained at the 3- and 6-month follow-up assessments. Conclusions Preliminary efficacy of the Growing, Learning, and Living With Autism Group was established. Based on parent report at the conclusion of the intervention, this is a socially valid intervention for teaching social communication and self-regulation skills to school-age children with ASD. Supplemental Material

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9. Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY. A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex. Neurology ;2019 (Jul 9) ;93(2):e200-e209.

OBJECTIVE : To investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC). METHODS : In this 12-month, randomized, double-blind, placebo-controlled trial, we attempted to enroll 60 children with TSC and IQ <80, learning disability, special schooling, or autism, aged 4-17 years, without intractable seizures to be assigned to receive everolimus or placebo. Everolimus was titrated to blood trough levels of 5-10 ng/mL. Primary outcome was full-scale IQ ; secondary outcomes included autism, neuropsychological functioning, and behavioral problems. RESULTS : Thirty-two children with TSC were randomized. Intention-to-treat analysis showed no benefit of everolimus on full-scale IQ (treatment effect -5.6 IQ points, 95% confidence interval -12.3 to 1.0). No effect was found on secondary outcomes, including autism and neuropsychological functioning, and questionnaires examining behavioral problems, social functioning, communication skills, executive functioning, sleep, quality of life, and sensory processing. All patients had adverse events. Two patients on everolimus and 2 patients on placebo discontinued treatment due to adverse events. CONCLUSIONS : Everolimus did not improve cognitive functioning, autism, or neuropsychological deficits in children with TSC. The use of everolimus in children with TSC with the aim of improving cognitive function and behavior should not be encouraged in this age group. CLINICALTRIALSGOV IDENTIFIER : NCT01730209. CLASSIFICATION OF EVIDENCE : This study provides Class I evidence that for children with TSC, everolimus does not improve intellectual disability, autism, behavioral problems, or other neuropsychological deficits.

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10. Parsons D, Wilson NJ, Vaz S, Lee H, Cordier R. Appropriateness of the TOBY Application, an iPad Intervention for Children with Autism Spectrum Disorder : A Thematic Approach. J Autism Dev Disord ;2019 (Jul 9)

This study aimed to explore the appropriateness of an ICT intervention, the Therapeutic Outcomes by You application (TOBY app), from the perspectives of the parents. Parental experiences of twenty-four parents of a child with ASD who had participated in a three-month trial using the TOBY app were collected using semi-structured interviews. Thematic analysis was conducted and themes were mapped against an appropriateness framework. Collectively, parents felt the TOBY app was relevant and important to them and their children’s needs, while expressing partial support of the TOBY app as : a positive experience for them and their children, beneficial for them and their children, a socially and ecological valid intervention, and an intervention that supported change and continuation in the skills learnt.

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11. Pua EPK, Ball G, Adamson C, Bowden S, Seal ML. Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders. Sci Rep ;2019 (Jul 9) ;9(1):9898.

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100 ; n = 84 males ; mean age : 11.43 years ; mean IQ : 110.58) was strictly matched to a control participant (n = 100 ; n = 84 males ; mean age : 11.43 years ; mean IQ : 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features, p = 0.01, n = 5000 permutations ; 10 surface area features, p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.

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12. Rydzewska E, Hughes-McCormack LA, Gillberg C, Henderson A, MacIntyre C, Rintoul J, Cooper SA. Age at identification, prevalence and general health of children with autism : observational study of a whole country population. BMJ Open ;2019 (Jul 9) ;9(7):e025904.

OBJECTIVES : Reported childhood prevalence of autism varies considerably between studies and over time, and general health status has been little investigated. We aimed to investigate contemporary prevalence of reported autism by age, and general health status of children/young people with and without autism. DESIGN : Secondary analysis of Scotland’s Census, 2011 data. Cross-sectional study. SETTING : General population of Scotland. PARTICIPANTS : All children (n=916 331) and young people (n=632 488) in Scotland. MAIN OUTCOME MEASURES : Number (%) of children/young people reported to have autism and their general health status ; prevalence of autism ; prevalence of poor health (fair, bad and very bad health) ; odds ratios (95% confidence intervals) of autism predicting poor health, adjusted for age and gender and OR for age and gender in predicting poor health within the population with reported autism. RESULTS : Autism was reported for 17 348/916 331 (1.9%) children aged 0-15, and 7715/632 488 (1.2%) young people aged 16-24. The rate increased to age 11 in boys and age 10 in girls, reflecting age at diagnosis. Prevalence was 2.8% at age 10 (4.4% for boys ; 1.1% for girls), and 2.9% at age 11 (4.5% for boys ; 1.1% for girls). 22.0% of children and 25.5% of young people with autism reported poor health, compared with 2.0% and 4.4% without autism. Autism had OR=11.3 (11.0 to 11.7) in predicting poor health. Autistic females had poorer health than autistic males, OR=1.6 (1.5 to 1.8). CONCLUSION : Accurate information on the proportion of autistic children and their health status is essential plan appropriate prevention and intervention measures and provide resources for those who may put demand on services designed for autistic people.

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13. Vasilevska Petrovska I, Trajkovski V. Effects of a Computer-Based Intervention on Emotion Understanding in Children with Autism Spectrum Conditions. J Autism Dev Disord ;2019 (Jul 9)

This randomized controlled study evaluated a computer-based intervention on emotion understanding in 32 children with autism spectrum conditions with and without intellectual disability (ID) aged 7-15 years. The intervention group (n = 16) used the program for 12 h while the control group (n = 16) was not included in any intervention or training beside the usual educational curriculum. After controlling for pre-intervention scores and symptom severity, strong positive effects were observed in emotion recognition from real face photographs and pictograms, as well as in understanding situation-based emotion across both intellectual ability groups. The typical and ID intervention groups performed significantly better on all EU measures, compared to controls, at the level of feature based distant generalization.

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