Pubmed du 31/08/19

samedi 31 août 2019

1. Barker-Haliski M, Steve White H. Validated animal models for antiseizure drug (ASD) discovery : Advantages and potential pitfalls in ASD screening. Neuropharmacology ;2019 (Aug 27):107750.

Since 1993, over 20 new anti-seizure drugs (ASDs) have been identified in well-established animal seizure and epilepsy models and subsequently demonstrated to be clinically effective in double-blinded, placebo-controlled clinical trials in patients with focal onset seizures. All clinically-available ASDs on the market today are effective in at least one of only three preclinical seizure and epilepsy models : the acute maximal electroshock (MES), the acute subcutaneous pentylenetetrazol (scPTZ) test, or the kindled rodent with chronic evoked seizures. Thus, it reasons that preclinical ASD development does not need significant revision to successfully identify ASDs for the symptomatic treatment of epilepsy. Unfortunately, a significant need still persists for more efficacious and better tolerated ASDs. This is particularly true for those patients whose seizures remain drug resistant. This review will focus on the continued utility of the acute MES and scPTZ tests, as well as the kindled rodent for current and future ASD development. These are the only "clinically validated" rodent models to date and been heavily used in the search for novel and more efficacious ASDs. This is to say that promising ASDs have been brought to the clinic on the basis of efficacy in these particular seizure and epilepsy models alone. This review also discusses some of the inherent advantages and limitations of these models relative to existing and emerging preclinical models. It then offers insight into future efforts to develop a preclinical model that will advance a truly transformative therapy for the symptomatic treatment of difficult to treat focal onset epilepsy.

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2. Bednarz HM, Kana RK. Patterns of Cerebellar Connectivity with Intrinsic Connectivity Networks in Autism Spectrum Disorders. J Autism Dev Disord ;2019 (Aug 31)

There is growing evidence of altered connectivity in autism spectrum disorders (ASD) between the cerebellum and cortex. Three intrinsic connectivity networks (ICNs) are especially important to cognitive processing in ASD : the default mode network (DMN), executive control network (ECN), and salience networks (SNs). The goal of this study was to compare resting-state functional connectivity between the cerebellum and the DMN, ECN, and SN in ASD and typically developing children (n = 74, ages 7-12 years). Children with ASD showed stronger connectivity between the ventral DMN and left cerebellar lobules I-IV. No meaningful relationships were observed between ICN-cerebellar functional connectivity and ASD symptoms. These results suggest that the cerebellum contributes to altered network connectivity in ASD.

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3. Churruca K, Ellis LA, Long JC, Pomare C, Wiles LK, Arnolda G, Ting HP, Woolfenden S, Sarkozy V, de Wet C, Hibbert P, Braithwaite J. The Quality of Care for Australian Children with Autism Spectrum Disorders. J Autism Dev Disord ;2019 (Aug 31)

Knowledge about the quality of care delivered to children with autism spectrum disorders (ASD) in relation to that recommended by clinical practice guidelines (CPGs) is limited. ASD care quality indicators were developed from CPGs and validated by experts, then used to assess the quality of care delivered by general practitioners (GPs) and pediatricians in Australia. Data were retrospectively collected from the medical records of 228 children (</= 15 years) with ASD for 2012-2013. Overall quality of care was high, but with considerable variation among indicators, and between GPs and pediatricians-e.g., GPs were less likely to complete the assessment care bundle (61% ; 95% CI 21-92). Findings highlight potential areas for improvement in the need for standardized criteria for diagnosis.

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4. Condy EE, Factor RS, Swain DM, Strege MV, Scarpa A. Maternal Affect During a Challenging Mother-Child Interaction : The Effects of Broad Autism Phenotype and Respiratory Sinus Arrhythmia Reactivity in Mothers of Children With and Without Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Aug 31)

Respiratory sinus arrhythmia (RSA) is proposed to index cognitive and behavioral inflexibility. Broad autism phenotype (BAP) traits are prevalent in family members of children with autism spectrum disorder (ASD). The study investigated whether RSA and BAP traits in mothers of typically developing (TD) children and mothers of children with ASD influence maternal affect. It was hypothesized that these factors would interact to influence mother-child interactions. Twenty-three mother-child dyads participated in a challenging interaction while measuring mother’s RSA. Results indicated that mothers of children with ASD show different RSA reactivity than mothers of TD children. Furthermore, preliminary analyses revealed RSA reactivity moderated the relationship between mothers’ rigidity and maternal affect during this interaction. Implications for future research and interventions are discussed.

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5. Corona LL, Janicki C, Milgramm A, Christodulu KV. Brief Report : Reductions in Parenting Stress in the Context of PEERS-A Social Skills Intervention for Adolescents with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Aug 31)

Social skills intervention is an evidence-based practice for enhancing communication and interpersonal skills in individuals with autism spectrum disorder (ASD). Participation in the Program for the Education and Enrichment of Relational Skills (PEERS(R)), a manualized social skills intervention for adolescents with ASD, is associated with improved social skills and peer interactions, as well as decreased autism symptoms. Participation in PEERS(R) has also been linked to increased parent self-efficacy and decreased family chaos. The present study examined parenting stress in the context of PEERS(R). Following participation in PEERS(R), parents reported lower levels of parenting stress associated with adolescent mood and social isolation. These findings provide further evidence of the family-wide benefits of adolescent-focused social skills intervention.

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6. Demirci E, Guler Y, Ozmen S, Canpolat M, Kumandas S. Levels of Salivary Sialic Acid in Children with Autism Spectrum Disorder ; Could It Be Related to Stereotypes and Hyperactivity ?. Clin Psychopharmacol Neurosci ;2019 (Aug 31) ;17(3):415-422.

Objective : Sialic acid (Sia) is an essential nutrient for brain development, learning, memory and cognition and plays a role in neurodevelopment of infants. The aim of this study was to determine whether Sia levels are signi fi cantly associated with the autism spectrum disorder (ASD). Methods : Forty-six ASD children and 30 typically developing children aged 3 to 10 years were included in the study. Behavioral symptoms in ASD children was assessed by the Autism Behavior Checklist (AuBC), the Childhood Autism Rating Scale, and the Aberrant Behavior Checklist (ABC). After the collection of saliva samples, the supernatant was separated. All the samples kept at -80 degrees C until Sia analysis was done. Results : Sia level was found to be significantly lower in the ASD group when compared to healthy controls ( p = 0.013). There was no correlation between severity of ASD and salivary Sia levels. We found a negative correlation between AuBC scores and Sia levels and a negative correlation in both ABC Stereotypic Behavior and Hyperactivity/Noncompliance subscales with Sia levels in ASD group. Conclusion : The obtained data indicate that Sia levels could have an effect on autism-like behaviors, particularly on stereotypes and hyperactivity.

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7. Eckert EM, Dominick KC, Pedapati EV, Wink LK, Shaffer RC, Andrews H, Choo TH, Chen C, Kaufmann WE, Tartaglia N, Berry-Kravis EM, Erickson CA. Pharmacologic Interventions for Irritability, Aggression, Agitation and Self-Injurious Behavior in Fragile X Syndrome : An Initial Cross-Sectional Analysis. J Autism Dev Disord ;2019 (Aug 29)

Using a dataset involving 415 individuals with irritability, aggression, agitation and self-injury (IAAS) behaviors from the fragile X syndrome (FXS) FORWARD database, we describe the psychopharmacologic management of IAAS and features of the population of persons with FXS treated with drug therapy for IAAS. Among those with FXS exhibiting IAAS, individuals with FXS receiving drug treatment of IAAS were older, more predominantly male, have more significant intellectual disability, more like to have comorbid autism, hyperarousal, and social impairments. The most commonly utilized medications for IAAS in FXS are antipsychotic medications, specifically aripiprazole and risperidone (37% and 27%, respectively). The majority of subjects (63%) experienced no side effects noted from the use of their psychopharmacologic medications.

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8. Edgar JC. Identifying electrophysiology markers of autism spectrum disorder and schizophrenia against a backdrop of normal brain development. Psychiatry Clin Neurosci ;2019 (Aug 31)

An examination of EEG and MEG studies demonstrates how age-related changes in brain neural function temporally constrain their use as diagnostic markers. A first example shows that, given maturational changes in the resting-state peak alpha frequency in typically developing children (TDC) but not in children who have autism spectrum disorder (ASD), group differences in alpha-band activity characterize only a subset of children who have ASD. A second example, auditory encoding processes in schizophrenia (SZ), shows that the complication of normal age-related brain changes on detecting and interpreting group differences in neural activity is not specific to children. MRI studies reporting group differences in the rate of brain maturation demonstrate that a group difference in brain maturation may be a concern for all diagnostic brain markers. Attention to brain maturation is needed whether one takes a DSM or a Research Domain Criteria (RDoC) approach to research. For example, although there is interest in cross-diagnostic studies comparing brain measures in ASD and SZ, such studies are difficult given that measures are obtained in one group well after and in the other much closer to the onset of symptoms. In addition, given differences in brain activity between infant, toddler, child, adolescent, and young and old adults, creating tasks and research designs that produce interpretable findings across the lifespan, yet allow for development, is difficult at best. To conclude, brain imaging findings show an effect of brain maturation on diagnostic markers separate from (and potentially difficult to distinguish from) effects of disease processes. Available research with large samples already provides direction about the age range(s) when diagnostic markers are most robust and informative. This article is protected by copyright. All rights reserved.

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9. Joshi G, DiSalvo M, Faraone SV, Wozniak J, Fried R, Galdo M, Belser A, Hoskova B, Dallenbach NT, De Leon MF, Biederman J. Predictive utility of autistic traits in youth with ADHD : a controlled 10-year longitudinal follow-up study. Eur Child Adolesc Psychiatry ;2019 (Aug 29)

The objective of this study was to investigate the stability and predictive utility of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD). Participants were referred youth with and without ADHD, without a diagnosis of autism spectrum disorder, and their siblings, derived from identically designed longitudinal case-control family studies of boys and girls with ADHD. Subjects were assessed with structured diagnostic interviews and measures of social, cognitive, and educational functioning. The presence of ATs at baseline was operationalized using a unique profile of the Child Behavior Checklist (CBCL) consisting of an aggregate T score of >/= 195 on the Withdrawn, Social, and Thought Problems subscales (CBCL-AT profile). At the follow-up, 83% of the ADHD youth with a positive AT profile at baseline continued to have a positive CBCL-AT profile. The presence of a positive CBCL-AT profile at baseline in youth with ADHD heralded a more compromised course characterized by a greater burden of psychopathology that emerged at an earlier age, along with poorer interpersonal, educational, and neurocognitive outcomes. Findings indicate a high level of persisting ATs in ADHD youth over time, as indexed through the CBCL-AT profile, and the presence of this profile prognosticates a compromised course in adult life in multiple domains of functioning.

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10. Lin S, El Idrissi A. Role of Taurine in Testicular Function in the Fragile x Mouse. Adv Exp Med Biol ;2019 ;1155:155-162.

Fragile X syndrome is an X-linked dominant disorder and the most common cause of inherited mental retardation. It is caused by trinucleotide repeat expansion in the fragile X mental retardation 1 gene (FMR1) at the Xq27.3. The expansion blocks expression of the gene product, Fragile X Mental Retardation Protein (FMRP). The syndrome includes mild to moderate mental retardation and behavioral manifestations such as tactile defensiveness, gaze avoidance, repetitive motor mannerisms, perseverative (repetitive) speech, hyperarousal and it frequently includes seizures. This behavioral phenotype overlaps significantly with autism spectrum disorder. The knockout mice lack normal Fmr1 protein and show macro-orchidism, learning deficits, and hyperactivity. Consequently, this knockout mouse may serve as a valuable tool in the elucidation of the physiological role of FMR1 and the mechanisms involved in macroorchidism, abnormal behavior, abnormalities comparable to those of human fragile X patients. In this study we evaluated the effects of taurine on the testicular physiology to better understand the cellular mechanisms underlying macro-orchidism. We found that there was a significant decrease in the number of Leydig cells in the testis of fragile X mouse. Furthermore, the expression of somatostatin was drastically decreased and differential expression pattern of CDK5 in fragile X mouse testis. In the control testis, CDK is expressed in primary and secondary spermatids whereas in the Fmr1 ko mice CDK 5 is expressed mainly in spermatogonia. Taurine supplementation led to an increase in CDK5 expression in both controls and Ko mice. CDKs (Cyclin-dependent kinases) are a group of serine/threonine protein kinases activated by binding to a regulatory subunit cyclin. Over 20 functionally diverse proteins involved in cytoskeleton dynamics, cell adhesion, transport, and membrane trafficking act as CDK5 substrates elucidating the molecular mechanisms of CDK5 function. CDK5 phosphorylates a diverse list of substrates, implicating it in the regulation of a range of cellular processes. CDK5 is expressed in Leydig cells, Sertoli cells, spermatogonia and peritubular cells indicating a role in spermatogenesis. In this study we examined the expression levels of CDK5 and how it is affected by taurine supplementation in the testes and found that taurine plays an important role in testicular physiology and corrected some of the pathophysiology observed in the fragile x mouse testis.

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11. Manelis L, Meiri G, Ilan M, Flusser H, Michaelovski A, Faroy M, Kerub O, Dinstein I, Menashe I. Language regression is associated with faster early motor development in children with autism spectrum disorder. Autism Res ;2019 (Aug 30)

Language regression (LR) is a consistent and reproducible phenomenon that is reported by 25% of parents who have children with autism spectrum disorder (ASD). However, there is controversy regarding the etiological and clinical significance of this phenomenon. Here, we examined data from a cohort of 218 children with ASD from the Negev Autism Center in Israel. We identified 36 children with ASD who were reported to exhibit clear LR by their parent on three independent occasions and compared them to 104 children whose parents did not report any concern of regression (NR). We compared a variety of key developmental characteristics across these two groups. We found that the age at which children with ASD in the LR group achieve key developmental milestones of crawling, walking, and use of first words is significantly younger than the age of children in the NR group, and comparable to the age of typically developing children. In contrast, no differences were observed in physical growth characteristics such as head circumference, weight, or height between the groups. Furthermore, almost all children with LR were born close to full term (>35 weeks) and none had a history of hypotonia. Notably, despite their apparently typical early development, children with LR were diagnosed with more severe symptoms of ASD than children with NR. These results strengthen the motivation to continue and study LR among children with ASD and suggest that early detection and intervention studies of ASD may benefit from stratifying children into LR and NR groups. Autism Res 2019, 1-12. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The presence of language regression (LR) among children with autism is still a matter of scientific debate. Here, we show that children with autism and reported LR start to crawl, talk, and walk at the same age as other typically developing children and significantly earlier than other children with autism. These findings, along with other medical differences between these groups, suggest that children who experienced LR comprise a distinct subgroup within the autism spectrum.

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12. McKechanie AG, Barnicoat A, Trender-Gerhard I, Allison M, Stanfield AC. Fragile X-associated conditions : implications for the whole family. Br J Gen Pract ;2019 (Sep) ;69(686):460-461.

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13. Nijhof AD, Bird G. Self-processing in individuals with autism spectrum disorder. Autism Res ;2019 (Aug 30)

Research attempting to explain the social difficulties observed in autism spectrum disorder has focused predominantly on difficulties understanding others, but there are indications that self-referential processing is also atypical in autism. For example, infants who later get an autism diagnosis show a reduced response when hearing their own name. In addition, research suggests that the self-bias (the tendency to preferentially process information when self-relevant) is smaller or absent in autism. However, findings are mixed : researchers are yet to clarify exactly those aspects of self-processing which are atypical in autism and in what way they are atypical. To gain further insight into these issues, future studies should focus on whether and how different aspects of self-processing are related in both neurotypical and autistic individuals. Furthermore, the (a)typical development of different aspects of the self, as well as the impact of the self on different domains of cognitive processing, deserves further attention, requiring studies with participants in a wide age range. Finally, the use of neural measures of self-processing will be invaluable, given the recent hypothesis that autistic individuals may learn to compensate for difficulties by relying on neural pathways which differ from those utilised by neurotypical individuals. Autism Res 2019, 1-5. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Research has indicated that individuals with autism spectrum disorder show differences in the processing of self-relevant information. However, as yet, exactly how self-processing differs in autism remains unknown. To further our understanding of the self in autism, future studies should focus on the relationship between different aspects of self-processing, investigating brain activity as well as behaviour, across a wide range of ages.

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14. Scheeren AM, Koot HM, Begeer S. Stability and change in social interaction style of children with autism spectrum disorder : A 4-year follow-up study. Autism Res ;2019 (Aug 31)

Children with autism spectrum disorder (ASD) show atypical social behavior but vary in their social interaction style (SIS), ranging from social aloofness to awkward social approaches. In a 4-year follow-up study, we examined longitudinal stability and change of SIS in children and adolescents with ASD and a normal intellectual ability (n = 55 ; mean age Time 1 : 13 years ; mean age Time 2 : 17 years). Children’s SIS was assessed with a parent questionnaire, the Wing Subtypes Questionnaire. As expected, most participants (69%) showed SIS stability across the 4-year interval. Some participants (18%) shifted to a more typical or more active (but odd) SIS, while others (13%) shifted to a less typical or less active (but odd) SIS. A decrease in ASD symptoms predicted a shift toward a more typical or active SIS, but children’s age and receptive verbal ability did not. SISs may be a meaningful way to create ASD subgroups and thus offer a promising research venue to further disentangle the heterogeneous autism spectrum. Autism Res 2019, 1-8. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY : People with autism spectrum disorder (ASD) demonstrate different social interaction styles (SIS), ranging from social aloofness to awkward social approaches. We examined if and how SIS changes across a 4-year period in 55 children and adolescents with ASD (mean age Time 1 = 13 years ; mean age Time 2 = 17 years). Most children (69%) showed the same SIS at both time points, indicating that SIS might be a relatively stable trait across adolescence.

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15. Swiggum M, Grant L. Monitoring Procedural Pain and Distress in a Child With Rett Syndrome : A Case Report. Pediatr Phys Ther ;2019 (Aug 28)

BACKGROUND AND PURPOSE : Whole body vibration training is a viable option for children with Rett syndrome ; however, the positioning requirements and intense vibration may be interpreted as pain. CASE : A 13-year-old girl with a diagnosis of Rett syndrome, Stage IV, participated. The Individualized Numeric Rating Scale was developed in collaboration with the caregiver and scored by a physical therapist and student physical therapists during 16 sessions of whole body vibration training. OUTCOMES : The therapist and students reached 100% agreement on the Individualized Numeric Rating Scale ratings and successfully provided distractions to prevent pain and distress from reaching a level 5 out of 10 for 139 of 144 sessions. CONCLUSION : This is the first case in the literature to demonstrate use of the Individualized Numeric Rating Scale with a child who is nonverbal during a potentially painful physical therapy procedure.

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16. Van der Donck S, Dzhelyova M, Vettori S, Thielen H, Steyaert J, Rossion B, Boets B. Fast Periodic Visual Stimulation EEG Reveals Reduced Neural Sensitivity to Fearful Faces in Children with Autism. J Autism Dev Disord ;2019 (Aug 29)

We objectively quantified the neural sensitivity of school-aged boys with and without autism spectrum disorder (ASD) to detect briefly presented fearful expressions by combining fast periodic visual stimulation with frequency-tagging electroencephalography. Images of neutral faces were presented at 6 Hz, periodically interleaved with fearful expressions at 1.2 Hz oddball rate. While both groups equally display the face inversion effect and mainly rely on information from the mouth to detect fearful expressions, boys with ASD generally show reduced neural responses to rapid changes in expression. At an individual level, fear discrimination responses predict clinical status with an 83% accuracy. This implicit and straightforward approach identifies subtle deficits that remain concealed in behavioral tasks, thereby opening new perspectives for clinical diagnosis.

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17. Wang Q, Wall CA, Barney EC, Bradshaw JL, Macari SL, Chawarska K, Shic F. Promoting Social Attention in 3-Year-Olds with ASD through Gaze-Contingent Eye Tracking. Autism Res ;2019 (Aug 30)

Young children with autism spectrum disorder (ASD) look less toward faces compared to their non-ASD peers, limiting access to social learning. Currently, no technologies directly target these core social attention difficulties. This study examines the feasibility of automated gaze modification training for improving attention to faces in 3-year-olds with ASD. Using free-viewing data from typically developing (TD) controls (n = 41), we implemented gaze-contingent adaptive cueing to redirect children with ASD toward normative looking patterns during viewing of videos of an actress. Children with ASD were randomly assigned to either (a) an adaptive Cue condition (Cue, n = 16) or (b) a No-Cue condition (No-Cue, n = 19). Performance was examined at baseline, during training, and post-training, and contrasted with TD controls (n = 23). Proportion of time looking at the screen (%Screen) and at actresses’ faces (%Face) was analyzed. At Pre-Training, Cue and No-Cue groups did not differ in %Face (P > 0.1). At Post-Training, the Cue group had higher %Face than the No-Cue group (P = 0.015). In the No-Cue group %Face decreased Pre- to Post-Training ; no decline was observed in the Cue group. These results suggest gaze-contingent training effectively mitigated decreases of attention toward the face of onscreen social characters in ASD. Additionally, larger training effects were observed in children with lower nonverbal ability, suggesting a gaze-contingent approach may be particularly relevant for children with greater cognitive impairment. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions. Autism Res 2019, 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : In this study, we leverage a new technology that combines eye tracking and automatic computer programs to help very young children with ASD look at social information in a more prototypical way. In a randomized controlled trial, we show that the use of this technology prevents the diminishing attention toward social information normally seen in children with ASD over the course of a single experimental session. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions.

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18. Williams ZJ, Failla MD, Davis SL, Heflin BH, Okitondo CD, Moore DJ, Cascio CJ. Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability. Sci Rep ;2019 (Aug 29) ;9(1):12595.

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7-54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of "perceptual noise." This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population.

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