Pubmed du 23/05/19

jeudi 23 mai 2019

1. Adams D, Paynter J, Clark M, Roberts J, Keen D. The Developmental Behaviour Checklist (DBC) Profile in Young Children on the Autism Spectrum : The Impact of Child and Family Factors. J Autism Dev Disord. 2019.

High levels of emotional/behavioural difficulties are frequently reported in children on the autism spectrum. However, given the diversity in profiles, there is a need to explore such behaviours in relation to individual factors. Parents of 130 children aged 4-5 on the autism spectrum completed measures of behaviour and adaptive behaviour. Hierarchical multiple regressions explored child and family characteristics in relation to children’s emotional/behavioural presentation. Different aspects of the behavioural profile were associated with different factors, with child autism characteristics, medication use, and parent mental health making significant unique contributions to a range of behavioural subscales. Understanding individual profiles beyond total scores is therefore needed to truly understand the emotional and behavioural profile of specific subgroups.

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2. Andrade C, Sahoo S, Solanki C, Narasimha VL, Nagendrappa S, Harshe D, Suhas S, Dharmadhikari A, Karki U, Pinto EF, Garag S, Tharayil HM, Mahadevan J. Development & validation of the Chandigarh autism screening instrument. The Indian journal of medical research. 2019 ; 149(1) : 74-5.

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3. Anthony BJ, Robertson HA, Verbalis A, Myrick Y, Troxel M, Seese S, Anthony LG. Increasing autism acceptance : The impact of the Sesame Street "See Amazing in All Children" initiative. Autism. 2019 : 1362361319847927.

To promote knowledge and acceptance of autism, Sesame Workshop created an online initiative : See Amazing in All Children. This nationwide evaluation of See Amazing assessed whether it increased knowledge and acceptance, promoted community inclusion, reduced parenting strain, and enhanced parenting competence. Survey responses were collected online from parents of children (age 6) with and without autism before (N = 1010), 1 week after (N = 510), and, for parents of autistic children, 1 month after (N = 182) they viewed the See Amazing materials. Following exposure, parents of non-autistic children showed small but significant increases in knowledge of autism and, like parents of autistic children, greater acceptance of autistic children. Parents of autistic children reported less strain, increased parenting competence, and more hope about involving their child in their community. That the See Amazing materials invoked positive changes in the general parent community and in parents of autistic children suggests that See Amazing materials have the potential to be an effective resource to increase acceptance and community inclusion, although limitations of self-selection, dropout rate, and lack of control group constrain interpretation. Implications include support for targeting acceptance as a step beyond awareness campaigns, though actual behavior change is a subject for future research.

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4. Can K, Menzfeld C, Rinne L, Rehling P, Kugler S, Golubiani G, Dudek J, Muller M. Neuronal Redox-Imbalance in Rett Syndrome Affects Mitochondria as Well as Cytosol, and Is Accompanied by Intensified Mitochondrial O 2 Consumption and ROS Release. Frontiers in physiology. 2019 ; 10 : 479.

Rett syndrome (RTT), an X chromosome-linked neurodevelopmental disorder affecting almost exclusively females, is associated with various mitochondrial alterations. Mitochondria are swollen, show altered respiratory rates, and their inner membrane is leaking protons. To advance the understanding of these disturbances and clarify their link to redox impairment and oxidative stress, we assessed mitochondrial respiration in defined brain regions and cardiac tissue of male wildtype (WT) and MeCP2-deficient (Mecp2(-/y) ) mice. Also, we quantified for the first time neuronal redox-balance with subcellular resolution in cytosol and mitochondrial matrix. Quantitative roGFP1 redox imaging revealed more oxidized conditions in the cytosol of Mecp2(-/y) hippocampal neurons than in WT neurons. Furthermore, cytosol and mitochondria of Mecp2(-/y) neurons showed exaggerated redox-responses to hypoxia and cell-endogenous reactive oxygen species (ROS) formation. Biochemical analyzes exclude disease-related increases in mitochondrial mass in Mecp2(-/y) hippocampus and cortex. Protein levels of complex I core constituents were slightly lower in Mecp2(-/y) hippocampus and cortex than in WT ; those of complex V were lower in Mecp2(-/y) cortex. Respiratory supercomplex-formation did not differ among genotypes. Yet, supplied with the complex II substrate succinate, mitochondria of Mecp2(-/y) cortex and hippocampus consumed more O2 than WT. Furthermore, mitochondria from Mecp2(-/y) hippocampus and cortex mediated an enhanced oxidative burden. In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT.

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5. Chen Q, Qiao Y, Xu XJ, Tao Y, You X. Urine Organic Acids as Potential Biomarkers for Autism-Spectrum Disorder in Chinese Children. Frontiers in cellular neuroscience. 2019 ; 13 : 150.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lacks clear biological biomarkers. Existing diagnostic methods focus on behavioral and performance characteristics, which complicates the diagnosis of patients younger than 3 years-old. The purpose of this study is to characterize metabolic features of ASD that could be used to identify potential biomarkers for diagnosis and exploration of ASD etiology. We used gas chromatography-mass spectrometry (GC/MS) to evaluate major metabolic fluctuations in 76 organic acids present in urine from 156 children with ASD and from 64 non-autistic children. Three algorithms, Partial Least Squares-Discriminant Analysis (PLS-DA), Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost), were used to develop models to distinguish ASD from typically developing (TD) children and to detect potential biomarkers. In an independent testing set, full model of XGBoost with all 76 acids achieved an AUR of 0.94, while reduced model with top 20 acids discovered by voting from these three algorithms achieved 0.93 and represent a good collection of potential ASD biomarkers. In summary, urine organic acids detection with GC/MS combined with XGBoost algorithm could represent a novel and accurate strategy for diagnosis of autism and the discovered potential biomarkers could be valuable for future research on the pathogenesis of autism and possible interventions.

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6. Guo Q, Ebihara K, Fujiwara H, Toume K, Awale S, Araki R, Yabe T, Dong E, Matsumoto K. Kami-shoyo-san ameliorates sociability deficits in ovariectomized mice, a putative female model of autism spectrum disorder, via facilitating dopamine D1 and GABAA receptor functions. Journal of ethnopharmacology. 2019 ; 236 : 231-9.

ETHNOPHARMACOLOGICAL RELEVANCE : Kami-shoyo-san (KSS) is a Kampo formula used clinically for menopause-related symptoms in Japan. However, the effect of KSS on autism spectrum disorder (ASD), a developmental disorder with a higher prevalence in males than in females, has not been reported yet. AIM OF THE STUDY : It is accepted generally that dysfunction in the GABAergic system is associated with pathogenesis of ASD. In our previous study, a decrease in brain allopregnanolone (ALLO), a positive allosteric GABAA receptor modulator, induced ASD-like symptoms such as impaired sociability-related performance and increased repetitive self-grooming behavior in male mice, and that KSS ameliorated these behavioral abnormalities via GABAA receptor- and dopamine D1 receptor-mediated mechanisms. In this study, to better understand a gender difference in the prevalence of ASD, we examined whether dissection of ovary (OVX), a major organ secreting progesterone in females, causes ASD-like behaviors in a manner dependent on brain ALLO levels, and if so, how KSS affects the behaviors. MATERIALS AND METHODS : Six-week-old ICR female mice received ovariectomy, and KSS (74mg/kg and 222mg/kg, p.o.) were treated before 1h starting each behavioral test. The sociability, social anxiety-like behavior, and self-grooming behavior were analyzed by the resident-intruder test, mirror chamber test, and open field test, respectively. After finishing the behavioral experiment, the ALLO content in the brain was measured by ELISA. Furthermore, we examined the effects of OVX on the neuro-signaling pathways in the prefrontal cortex and striatum by Western blotting. RESULTS : The results revealed that OVX induced sociability deficits and social anxiety-related behaviors, but not repetitive self-grooming behavior, and that these behavioral changes were accompanied not only by a decrease of brain ALLO levels, but also by impairment of CREB- and CaMKIIalpha-mediated neuro-signaling in the prefrontal cortex. Moreover, the administration of KSS had no effect on the brain ALLO level, but significantly ameliorated the OVX-induced behavioral and neurochemical changes via facilitation of GABAA receptor and dopamine D1 receptor-mediated neurotransmission. CONCLUSIONS : These findings suggest that a decrease in gonadal hormone-derived ALLO plays a major role in ASD-like behaviors in female mice and that KSS is beneficial for the treatment of ASD in females.

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7. Gurney ME, Nugent RA, Mo X, Sindac JA, Hagen TJ, Fox D, 3rd, O’Donnell JM, Zhang C, Xu Y, Zhang HT, Groppi VE, Bailie M, White RE, Romero DL, Vellekoop AS, Walker JR, Surman MD, Zhu L, Campbell RF. Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. J Med Chem. 2019 ; 62(10) : 4884-901.

Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compounds was based on iterative analysis of X-ray crystal structures combined with metabolite identification. Selectivity for the activated, dimeric form of PDE4D provided potent memory enhancing effects in a mouse model of novel object recognition with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors that lack subtype selectivity. The lead compound, 28 (BPN14770), has entered midstage, human phase 2 clinical trials for the treatment of Fragile X Syndrome.

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8. Khatri N, Man HY. The Autism and Angelman Syndrome Protein Ube3A/E6AP : The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions. Front Mol Neurosci. 2019 ; 12 : 109.

UBE3A is a gene implicated in neurodevelopmental disorders. The protein product of UBE3A is the E3 ligase E6-associated protein (E6AP), and its expression in the brain is uniquely regulated via genetic imprinting. Loss of E6AP expression leads to the development of Angelman syndrome (AS), clinically characterized by lack of speech, abnormal motor development, and the presence of seizures. Conversely, copy number variations (CNVs) that result in the overexpression of E6AP are strongly associated with the development of autism spectrum disorders (ASDs), defined by decreased communication, impaired social interest, and increased repetitive behavior. In this review article, we focus on the neurobiological function of Ube3A/E6AP. As an E3 ligase, many functional target proteins of E6AP have been discovered, including p53, Arc, Ephexin5, and SK2. On a neuronal level, E6AP is widely expressed within the cell, including dendritic arbors, spines, and the nucleus. E6AP regulates neuronal morphological maturation and plays an important role in synaptic plasticity and cortical development. These molecular findings provide insight into our understanding of the molecular events underlying AS and ASDs.

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9. Krol M, Krol M. The world as we know it and the world as it is : Eye-movement patterns reveal decreased use of prior knowledge in individuals with autism. Autism Res. 2019.

We used a perceptual closure task with Mooney images as stimuli to record eye-movement patterns in response to the same degraded image before and after perceptual learning in 21 adolescents and young adults with ASD and 23 sex-, age-, and IQ-matched typically developing individuals. In the control group, we observed changes in the eye-movement patterns between the first and the last presentation of the degraded stimulus, reflecting top-down optimization of eye-movement patterns, that is, a decrease in the number of fixations and interfixation distance, coupled with an increase in the duration of fixations. This effect was attenuated in individuals with autism, pointing to a decreased rate of perceptual learning. We also found that participants with autism displayed decreased scanpath stability, that is, a lower recurrence of fixation locations between different presentations of the same image, which may suggests a lower rate of perceptual learning or decreased predictability in the eye-movement patterns. These results provide evidence for decreased use of prior knowledge in perceptual decisions in autism. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : We showed autistic and typically developing participants some degraded images that were difficult to recognize for the first time, but once you knew what they represent, you could see it easily. We found that the eye-movement patterns of persons with autism did not change as much after learning what the pictures represented as in the case of typically developing participants. This means that previous experiences and knowledge change the way people with autism perceive things to a smaller extent.

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10. Leung CNW, Chan RWS, Yeung MYC, Tsui HCH. Applicability and Effectiveness of Social Competence Group Intervention on Adults with Autism Spectrum Disorder in a Chinese Context : A Community-Based Study with Self- and Parent-Report. J Autism Dev Disord. 2019.

Social competence training for adults with ASD were limited in comparison to intervention for children or adolescents. CBT-CSCA is a culturally-sensitive social competence training specially developed for adolescents in Hong Kong. With its demonstrated effectiveness, the current study outlined the adaptions of its adult version, CBT-CSCA (Adult) and examined its treatment effectiveness. Thirty-six adults (aged 18-29 years, with a FSIQ above 80) completed the intervention. Significant improvements were shown in overall social competence, from both self- and parent-report, and negative mood. Participants also reported satisfactory knowledge gain and confidence in applying content learnt after each session. The study provided evidence support to the applicability and effectiveness of social competence training for adults with ASD in the Chinese culture.

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11. Roche L, Carnett A, Sigafoos J, Stevens M, O’Reilly MF, Lancioni GE, Marschik PB. Using a Textual Prompt to Teach Multiword Requesting to Two Children With Autism Spectrum Disorder. Behav Modif. 2019 : 145445519850745.

Autism spectrum disorder is characterized by social and communication impairment, but some children appear to have relative strength in areas such as reading printed words. The present study involved two children with limited expressive communication skills, but relatively stronger reading ability. Based on this existing strength, we evaluated a textual prompting procedure for teaching the children to produce multiword spoken requests. The effect of providing textual prompts on production of multiword requests was evaluated in an ABAB design. The results showed that multiword requests increased when textual prompts were provided and decreased when the prompts were removed. In subsequent phases, the textual prompts were successfully faded by gradually making the printed text lighter and lighter until eventually the prompts were eliminated altogether. We conclude that identification of children’s strengths may assist in identifying effective prompting procedures that could then be used in teaching functional communication skills.

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12. Zarafshan H, Mohammadi MR, Abolhassani F, Motevalian SA, Sepasi N, Sharifi V. Current Status of Health and Social Services for Children with Autism in Iran : Parents’ Perspectives. Iranian journal of psychiatry. 2019 ; 14(1) : 76-83.

Objective : The present study is a part of a larger study that aimed at developing a comprehensive model of service delivery for individuals with autism in Iran based on the local needs and characteristics. In this study, the status of the services provided to those with autism in Iran was investigated based on the perspectives of parents of children with autism. Method : A semi-structured interview was used to qualitatively investigate the status of the services with regards to autism in Iran based on the perspectives of parents of children with autism. Results : This study revealed several barriers, including shortness of eligible professionals, difficulty in access to care for families, high costs, and lack of formal and informal supports, in providing services to those with autism in Iran. Early detection and diagnosis are of prime importance. We also need to train our specialists to diagnose autism based on the standard protocols and tests. Conclusion : In sum, we need a comprehensive program that involves different sectors in charge of health and education in Iran.

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13. Zukerman G, Yahav G, Ben-Itzchak E. Diametrically opposed associations between academic achievement and social anxiety among university students with and without autism spectrum disorder. Autism Res. 2019.

Research findings indicate that anxiety, social anxiety in particular, is the most common experience reported by individuals with autism spectrum disorder (ASD) attending postsecondary education. Among students without ASD, higher levels of social anxiety have been postulated to correlate with impaired academic achievement ; restriction of one’s social network because of anxiety is thought to lead to reduction of access to resources important for learning such as social/emotional support and collaborative learning. However, despite growing interest in the outcomes of young students with ASD, no research has studied the associations between academic achievement and anxiety among students with ASD. This study examined the association between social anxiety and grade point average (GPA) among university students : 55 diagnosed with ASD, 31 without ASD but high levels of social anxiety, and 25 without ASD and with low levels of social anxiety (controls). GPAs were significantly lower for the ASD group than for the two non-ASD groups. Among students without ASD, a negative correlation between social anxiety and grades was observed whereas the reverse pattern was found for the ASD group, meaning that for students with ASD, higher levels of social anxiety were associated with higher grades. Additionally, in a regression analysis, ASD diagnosis, social anxiety, and the interaction of group x social anxiety significantly predicted GPA. Possible explanations for this finding, as well as implications for interventions among this population of high-functioning students with ASD, are discussed. Autism Res 2019. (c) 2019 International Society for AutismResearch,Wiley Periodicals, Inc. LAY SUMMARY : This study compared the relationship between levels of social anxiety and grades in students with autism spectrum disorder (ASD) and in students without ASD who had either high social anxiety or low social anxiety (controls). Among the group with ASD, higher levels of social anxiety were associated with higher grades, whereas the reverse pattern was found among the other groups. This finding’s implications for interventions among students with ASD are discussed.

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