Pubmed du 11/05/19

samedi 11 mai 2019

1. Al-Ayadhi L, El-Ansary A, Bjorklund G, Chirumbolo S, Mostafa GA. Impact of Auditory Integration Therapy (AIT) on the Plasma Levels of Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Autism Spectrum Disorder. J Mol Neurosci ;2019 (May 9)

Neurotrophic factors, including the glial cell line-derived neurotrophic factor (GDNF), are of importance for synaptic plasticity regulation, intended as the synapses’ ability to strengthen or weaken their responses to differences in neuronal activity. Such plasticity is essential for sensory processing, which has been shown to be impaired in autism spectrum disorder (ASD). This study is the first to investigate the impact of auditory integration therapy (AIT) of sensory processing abnormalities in autism on plasma GDNF levels. Fifteen ASD children, aged between 5 and 12 years, were enrolled and underwent the present research study. AIT was performed throughout 10 days with a 30-min session twice a day. Before and after AIT, Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma GDNF levels were assayed by an EIA test. A substantial decline in autistic behavior was observed after AIT in the scaling parameters used. Median plasma GDNF level was 52.142 pg/ml before AIT. This level greatly increased immediately after AIT to 242.05 pg/ml (P < 0.001). The levels were depressed to 154.00 pg/ml and 125.594 pg/ml 1 month and 3 months later, respectively, but they were still significantly higher compared with the levels before the treatment (P = 0.001, P = 0.01, respectively). There was an improvement in the measures of autism severity as an effect of AIT which induced the up-regulation of GDNF in plasma. Further research, on a large scale, is needed to evaluate if the cognitive improvement of ASD children after AIT is related or not connected to the up-regulation of GDNF.

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2. Baker EK, Arpone M, Aliaga SM, Bretherton L, Kraan CM, Bui M, Slater HR, Ling L, Francis D, Hunter MF, Elliott J, Rogers C, Field M, Cohen J, Cornish K, Santa Maria L, Faundes V, Curotto B, Morales P, Trigo C, Salas I, Alliende AM, Amor DJ, Godler DE. Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features. Mol Autism ;2019 ;10:21.

Background : Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM : 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM : >/= 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods : The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results : Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion : Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS.

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3. Bong G, Kim JH, Hong Y, Yoon NH, Sunwoo H, Jang JY, Oh M, Lee KS, Jung S, Yoo HJ. The Feasibility and Validity of Autism Spectrum Disorder Screening Instrument : Behavior Development Screening for Toddlers (BeDevel)-A Pilot Study. Autism Res ;2019 (May 10)

Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments, and the need for a culturally appropriate early screening tool in Korean children, led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts : BeDevel-Interview, a structured interview measure for parents/primary caregivers ; and BeDevel-Play, a play-based semi-structured observational measure in children. To examine the feasibility and validity of BeDevel, 155 children (N = 75 ASD, N = 55 typical development, N = 25 developmentally delayed) aged 18-42 months (M = 31.54 months, SD = 7.60) were examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When BeDevel items were analyzed using Cohen’s kappa statistics, most items in BeDevel-Interview and all items in BeDevel-Play were reasonably consistent with diagnoses. We identified primary items, which were significantly interacted with actual diagnosis in the chi-squared test (P < 0.05, range = 0.000-0.032). Using cutoff numbers of items determined using the receiver operating characteristics curve, BeDevel showed satisfactory levels of sensitivity (83.33%-100%), specificity (81.25%-100%), positive predictive values (80.65%-100%), and negative predictive values (83.87%-100%), as well as high internal consistency (Cronbach’s alpha = 0.866-959). The agreement between BeDevel and most other screening/diagnostic instruments was moderate (k = 0.419-1.000). These results suggest that BeDevel can be a useful instrument for early screening of ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments and the need for a culturally appropriate early screening tool in Korean children led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts : BeDevel-Interview, a structured interview measure for parents/primary caregivers ; and BeDevel-Play, a play-based, semi-structured observational measure in children. In order to test the feasibility and validity of BeDevel, we analyzed preliminary data of total 155 children aged 18-42 months, examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When individual items were analyzed, responses of all BeDevel-Interview items and of most BeDevel-Play items well matched actual diagnoses, and we identified primary items, which were particularly useful in differentiating between the ASD group and the non-ASD group. With the optimal screening criteria determined, the BeDevel was able to identify individuals with a diagnosis of ASD and those without it, all at satisfactory levels. Lastly, BeDevel items were closely related as a set, and the BeDevel screening results were reasonably consistent with the results of most other screening/diagnostic instruments. These results suggest that BeDevel can be a useful instrument for early screening of ASD.

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4. Bryant LK, Woynaroski TG, Wallace MT, Cascio CJ. Self-reported Sensory Hypersensitivity Moderates Association Between Tactile Psychophysical Performance and Autism-Related Traits in Neurotypical Adults. J Autism Dev Disord ;2019 (May 9)

Atypical responses to tactile stimulation have been linked to core domains of dysfunction in individuals with autism spectrum disorder (ASD) and phenotypic traits associated with ASD in neurotypical individuals. We investigated (a) the extent to which two psychophysically derived measures of tactile sensitivity-detection threshold and dynamic range-relate to traits associated with ASD and (b) whether those relations vary according to the presence of self-reported sensory hypersensitivities in neurotypical individuals. A narrow dynamic range was associated with increased autism-related traits in individuals who reported greater sensory hypersensitivity. In contrast, in individuals less prone to sensory hypersensitivity, a narrow dynamic range was associated with reduced autism-related traits. Findings highlight the potential importance of considering dynamic psychophysical metrics in future studies.

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5. Coban N, Gokcen C, Akbayram S, Calisgan B. Evaluation of Platelet Parameters in Children with Autism Spectrum Disorder : Elongated Collagen-Adenosine Diphosphate and Collagen-Epinephrine Closure Times. Autism Res ;2019 (May 11)

Changes related to the serotonin system play a key role in the etiology of autism spectrum disorder (ASD). Although we know that platelets are associated with the serotonin system, their relation to ASD has not yet been elucidated. In this study, we aim to investigate platelet parameters in children with ASD. Forty patients with ASD according to Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) and 30 healthy controls were included in the study. A complete blood count was done to measure parameters relating to platelet morphology. Moreover, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were evaluated. Lastly, platelet functions were assessed with a platelet functions analyzer 100 (PFA-100) device by measuring collagen-ADP and collagen-epinephrine (EPI) closure times. There was not a significant difference between the groups in terms of platelet count, mean platelet volume (MPV), platelet distribution width, plateletcrit, PT, or aPTT parameters for ASD patients when compared to the control group (P > 0.05). However, MPV in severe ASD, as quantified by the Childhood Autism Rating Scale, was found to be significantly lower when compared to mild to moderate ASD (P = 0.047). Moreover, in terms of platelet functions, the elongation in collagen-ADP and collagen-EPI closure times were significantly higher for the ASD group (P = 0.044). These results may suggest an impairment in platelet functions rather than in platelet morphology for children with ASD. Considering these results, further investigation of thrombocyte functions in the ASD may lead to a better understanding of the pathogenesis of ASD and to the development of our limited knowledge of this disorder. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Serotonin is a chemical that is found in brain as wells as in blood cells that function in blood clotting in the human body. There are problems related to serotonin in brains of people who have autism. Thus, blood clotting cells may also be affected in people who have autism. In this study, we compare blood clotting functions of children with autism with that of healthy controls.

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6. Crandall MC, Bottema-Beutel K, McDaniel J, Watson LR, Yoder PJ. Children with Autism Spectrum Disorder May Learn from Caregiver Verb Input Better in Certain Engagement States. J Autism Dev Disord ;2019 (May 9)

The relation between caregiver follow-in utterances with verbs presented in different states of dyadic engagement and later child expressive verb vocabulary in children with autism spectrum disorder (ASD) was examined in 29 toddlers with ASD and their caregivers. Caregiver verb input in follow-in utterances presented during higher order supported joint engagement (HSJE) accounted for a significant, large amount of variance in later child verb vocabulary ; R(2)= .26. This relation remained significant when controlling for early verb vocabulary or verb input in lower support engagement states. Other types of talk in follow-in utterances in HSJE did not correlate with later verb vocabulary. These findings are an important step towards identifying interactional contexts that facilitate verb learning in children with ASD.

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7. Gyawali S, Patra BN. Autism Spectrum Disorder : Trends in research exploring etiopathogenesis. Psychiatry Clin Neurosci ;2019 (May 11)

Autism Spectrum Disorder is a neurodevelopmental condition in which affected individuals have difficulties while interacting and communicating socially, and repetitive behaviors. It has a multi-factorial etiology. Various risk factors including genetic and environmental influences have been explored while trying to understand its causation. As older evidence was suggestive of a high heritability, a majority of research focused on finding the underlying genetic causes of autism. Due to these efforts, there have been advances in the knowledge of some of the genetic factors associated with autism. But a recent trend also shows an increasing interest in exploration of various potential environmental triggers. These efforts have brought us closer to understanding the elusive disorder more so than ever before. The current paper discusses the recent trends in research exploring the etiopathogenesis of Autism Spectrum Disorders. This article is protected by copyright. All rights reserved.

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8. Liu XY, Xiao YK, Hwang E, Haeng JJ, Yi TH. Anti-photoaging and Anti-melanogenesis Properties of Ginsenoside C-Y, a Ginsenoside Rb2 Metabolite from American Ginseng PDD-ginsenoside. Photochem Photobiol ;2019 (May 10)

Ginsenosides are compounds responsible for the primary pharmacological effects of American ginseng. Compound-Y (C-Y) is a minor ginsenoside and a metabolite of Panax ginseng. In this study, we investigated the protective effect of ginsenoside UVB-irradiated NHDFs and its potential for use as an anti-hyperpigmentation agent through ginsenoside C-Y as a functional food and cosmetic ingredient. Ginsenoside C-Y is a natural antioxidant isolated from the American ginseng PDD-ginsenoside. Our data showed that ginsenoside C-Y block UVB-exposed ROS, restrict MMP-1 production, and promote procollagen type I synthesis. Interestingly, ginsenoside C-Y suppresses UVB-exposed VEGF, and TNF-alpha secretion, could be related with NFAT signal path. Ginsenoside C-Y has exhibited photoaging effects by increasing TGF-beta1 level, fortifying Nrf2 nuclear translocation, and restricting AP-1 and MAPK phosphorylation. Assessment of the melanogenic response indicated that ginsenoside C-Y inhibited melanin secretion and tyrosinase activity and decreased melanin content in melan-a and zebrafish embryos. These results suggest that ginsenoside C-Y can be used as a potential botanical agent to protect premature skin from UVB-induced photodamage and prevent skin hyperpigmentation. This article is protected by copyright. All rights reserved.

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9. Locke J, Kang-Yi C, Pellecchia M, Mandell DS. It’s Messy but Real : A Pilot Study of the Implementation a Social Engagement Intervention for Children with Autism in Schools. J Res Spec Educ Needs ;2019 (Apr) ;19(2):135-144.

Social impairment represents one of the most challenging core deficits of autism spectrum disorder (ASD) and greatly affects children’s school experiences ; however, few evidence-based social engagement programs have been implemented and sustained in schools. This pilot study examined the implementation and sustainment of a social engagement intervention, Remaking Recess, for four elementary-aged children with ASD and four school personnel in two urban public schools. The improved peer engagement and social network inclusion outcomes suggest that Remaking Recess can be feasibly implemented in under resourced public schools with fidelity and has the potential to improve child outcomes for children with ASD.

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10. Passalacqua C, Garcia M, Sepulveda E, Toledo D, Valencia M, Arancibia M. Psychological and cognitive evaluation of autism in a patient with MOMO syndrome : a case report and literature review. Medwave ;2019 (May 2) ;19(4):e7622.

MOMO is an acronym for macrosomia, obesity, macrocephaly and ocular abnormalities. The syndrome was first described in 1993, with a total of nine patients published thus far. All the cases presented intellectual disability and in one case autism was described. We present a new case of a patient with MOMO syndrome, who consulted for hallucinatory phenomena. He completed a neuropsychological, clinical and cognitive evaluation, showing a borderline intelligence quotient and fulfilled the criteria for autism spectrum disorder. This is the first neurocognitive evaluation of a patient with MOMO, supporting the use of standardized scales in order to assess the autism and other psychiatric comorbidities in patients with genetics syndromes.

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11. Raccio A. J. Newman : To Siri with Love : A Mother, Her Autistic Son, and the Kindness of Machines : HarperCollins, New York, NY, 2017. J Autism Dev Disord ;2019 (May 9)

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12. Strugnell A, Leonard H, Epstein A, Downs J. Using directed-content analysis to identify a framework for understanding quality of life in adults with Rett syndrome. Disabil Rehabil ;2019 (May 10):1-8.

PURPOSE : Rett syndrome (RTT) is a rare neurodevelopmental disorder mainly affecting females and is caused by a mutation in the MECP2 gene. Recent research identified the domains of quality of life (QOL) important for children with RTT but there has been no investigation of domains important for adults. This qualitative study explored QOL in adults with RTT and compared domains with those previously identified for children. METHODS : The sample comprised parents and/or primary caregivers of 20 adults, aged 18-38 years, who were registered with the Australian Rett Syndrome Database. Semi-structured telephone interviews were conducted to investigate aspects of life that were observed to be satisfying or challenging. Data were analyzed using directed content analysis, based on existing QOL domains for children with RTT that related to health and wellbeing, daily activities, and community immersion and services. RESULTS : Each of the domains identified for children with RTT was represented in the adult dataset, with no new domains emerging. CONCLUSION : This is the first study to identify QOL domains important for adults with RTT. Health and therapy needs are ongoing during adulthood but services may be limited. Findings will guide choice of an appropriate QOL measure for this group. IMPLICATIONS FOR REHABILITATION Knowing the important domains of quality of life enables clinicians and service providers to systematically review and address key management issues. Despite a high level of dependency and sometimes poor health, parent caregivers perceive potential for strong quality of life in adulthood. Services that maintain functional skills and health throughout the lifespan are valued for their support of quality of life in adults with Rett syndrome.

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13. Wan B, Wang Z, Jung M, Lu Y, He H, Chen Q, Jin Y. Effects of the Co-occurrence of Anxiety and Attention-Deficit/Hyperactivity Disorder on Intrinsic Functional Network Centrality among Children with Autism Spectrum Disorder. Autism Res ;2019 (May 10)

Children with autism spectrum disorder (ASD) present with a high co-occurrence of anxiety and attention-deficit/hyperactivity disorder (ADHD). However, it remains unclear how the co-occurrence of anxiety and ADHD in children with ASD alters whole-brain functional networks. Here, we aimed to examine anxiety- and ADHD-related brain network centrality in children with ASD separately and their relationships with ASD symptoms. Clinical anxiety and ADHD levels in children with ASD, aged 6-13 years old, were assessed. Participants were categorized into four groups : ASD only (n = 28), ASD + anxiety (n = 19), ASD + ADHD (n = 25), and ASD + both anxiety and ADHD (n = 28). Subsequently, we compared voxel-wise network degree centrality (DC) among the four groups. We found that : (a) compared with ASD only, children with ASD + anxiety showed higher DC in the left middle temporal gyrus, right lingual gyrus, and left cuneus, and lower DC in the right precuneus ; (b) children with ASD + ADHD presented higher DC in the right calcarine and left superior frontal gyrus (SFG) compared with ASD only ; (c) children with ASD + both displayed higher DC in the right calcarine and lower centrality in the right middle occipital gyrus compared with ASD only ; and (d) across all children with ASD, there was a positive correlation between DC of the right calcarine with nonverbal behavior scores, and DC of the left SFG was negatively correlated with social scores. Our findings suggest that the right calcarine, left SFG, and default mode network nodes play important roles in the co-occurrence of anxiety and ADHD among children with ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The co-occurrence of anxiety and attention-deficit/hyperactivity disorder (ADHD) has been shown to influence the brain function of children with ASD. In order to gain a better understanding of this, the present study compared degree centrality, the amount of effective brain functional connectivity that reflects the characteristics of brain networks, among four groups : ASD only, ASD + anxiety, ASD + ADHD, and ASD + both anxiety and ADHD. We found that some areas located in the language processing network and primary visual cortex were associated with the co-occurrence of ADHD, and some other areas located in the default mode network were associated with the co-occurrence of both anxiety and ADHD. These findings provide more knowledge about the neural basis underlying behavioral changes related to the co-occurrence of anxiety and ADHD in children with ASD.

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14. Wenhart T, Bethlehem RAI, Baron-Cohen S, Altenmuller E. Autistic traits, resting-state connectivity, and absolute pitch in professional musicians : shared and distinct neural features. Mol Autism ;2019 ;10:20.

Background : Recent studies indicate increased autistic traits in musicians with absolute pitch and a higher proportion of absolute pitch in people with autism. Theoretical accounts connect both of these with shared neural principles of local hyper- and global hypoconnectivity, enhanced perceptual functioning, and a detail-focused cognitive style. This is the first study to investigate absolute pitch proficiency, autistic traits, and brain correlates in the same study. Sample and methods : Graph theoretical analysis was conducted on resting-state (eyes closed and eyes open) EEG connectivity (wPLI, weighted phase lag index) matrices obtained from 31 absolute pitch (AP) and 33 relative pitch (RP) professional musicians. Small-worldness, global clustering coefficient, and average path length were related to autistic traits, passive (tone identification) and active (pitch adjustment) absolute pitch proficiency, and onset of musical training using Welch two-sample tests, correlations, and general linear models. Results : Analyses revealed increased path length (delta 2-4 Hz), reduced clustering (beta 13-18 Hz), reduced small-worldness (gamma 30-60 Hz), and increased autistic traits for AP compared to RP. Only clustering values (beta 13-18 Hz) were predicted by both AP proficiency and autistic traits. Post hoc single connection permutation tests among raw wPLI matrices in the beta band (13-18 Hz) revealed widely reduced interhemispheric connectivity between bilateral auditory-related electrode positions along with higher connectivity between F7-F8 and F8-P9 for AP. Pitch-naming ability and pitch adjustment ability were predicted by path length, clustering, autistic traits, and onset of musical training (for pitch adjustment) explaining 44% and 38% of variance, respectively. Conclusions : Results show both shared and distinct neural features between AP and autistic traits. Differences in the beta range were associated with higher autistic traits in the same population. In general, AP musicians exhibit a widely underconnected brain with reduced functional integration and reduced small-world property during resting state. This might be partly related to autism-specific brain connectivity, while differences in path length and small-worldness reflect other ability-specific influences. This is further evidenced for different pathways in the acquisition and development of absolute pitch, likely influenced by both genetic and environmental factors and their interaction.

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15. Zhang Y, Xiang Z, Jia Y, He X, Wang L, Cui W. The Notch signaling pathway inhibitor Dapt alleviates autism-like behavior, autophagy and dendritic spine density abnormalities in a valproic acid-induced animal model of autism. Prog Neuropsychopharmacol Biol Psychiatry ;2019 (May 7):109644.

Autism spectrum disorders (ASDs) comprise a number of heterogeneous neurodevelopmental diseases. Recent studies suggest that the abnormal transmission of neural signaling pathways is associated with the pathogenesis of autism. The aim of this study was to identify a link between the Notch signaling pathway and the pathogenesis of autism. In this study, we demonstrated that prenatal exposure to valproic acid (VPA) resulted in autistic-like behaviors in offspring rats and that the expression of the Notch signaling pathway-related molecules Notch1, Jagged1, Notch intracellular domain (NICD) and Hes1 increased in the prefrontal cortex (PFC), hippocampus (HC) and cerebellum (CB) of VPA rats compared to those of controls. However, inhibiting the Notch pathway with (3,5-Difluorophenacetyl)-L-alanyl-S-phenylglycine-2-butyl Ester (Dapt) reduced the overexpression of Notch pathway-related molecules in offspring rats. Notably, Dapt improved autistic-like behaviors in a VPA-exposed rat model of autism. Furthermore, we investigated whether Dapt improved autistic-like behavior in a VPA rat model by regulating autophagy and affecting the morphology of dendritic spines. We found that the expression of the autophagy-related proteins Beclin 1, LC3B and phospho-p62 in the PFC, HC and CB of VPA model rats increased after Notch signal activation and was inhibited by Dapt compared to those of controls. Moreover, postsynaptic density-95 (PSD-95) protein expression also increased significantly compared to that of VPA model rats. The density of dendritic spines decreased in the PFC of VPA rats treated with Dapt compared to that of VPA model rats. Our present results suggest that VPA induces an abnormal activation of the Notch signaling pathway. The inhibition of excessive Notch signaling activation by Dapt can alleviate autistic-like behaviors in VPA rats. Our working model suggests that the Notch signaling pathway participates in the pathogenesis of autism by regulating autophagy and affecting dendritic spine growth. The results of this study may help to elucidate the mechanism underlying autism and provide a potential strategy for treating autism.

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