Pubmed du 07/02/20

vendredi 7 février 2020

1. Bjorklund G, Meguid NA, El-Bana MA, Tinkov AA, Saad K, Dadar M, Hemimi M, Skalny AV, Hosnedlova B, Kizek R, Osredkar J, Urbina MA, Fabjan T, El-Houfey AA, Kaluzna-Czaplinska J, Gatarek P, Chirumbolo S. Oxidative Stress in Autism Spectrum Disorder. Mol Neurobiol. 2020.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites’ surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part ; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

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2. Brewe AM, Simmons GL, Capriola-Hall NN, White SW. Sluggish cognitive tempo : An examination of clinical correlates for adults with autism. Autism. 2020 : 1362361319900422.

LAY ABSTRACT : Adults with autism spectrum disorder often experience a range of co-occurring mental health problems such as attention-deficit/hyperactivity-disorder, as well as difficulties with executive function. Sluggish cognitive tempo, a cluster of behaviors including slow processing, daydreaming, and mental fogginess, has been shown to be associated with attention-deficit/hyperactivity-disorder, and limited research has suggested that individuals with autism spectrum disorder may experience sluggish cognitive tempo. We examined co-occurring mental health problems and executive function in 57 young adults with autism spectrum disorder, aged 16-25 years to better understand sluggish cognitive tempo in autism spectrum disorder. Parents of the young adults answered questions about their children’s sluggish cognitive tempo, attention-deficit/hyperactivity-disorder, depression, and anxiety symptoms, and the young adults completed tests of their executive function. Results demonstrated that nearly one-third of the sample exhibited clinically impairing levels of sluggish cognitive tempo. Although sluggish cognitive tempo and attention-deficit/hyperactivity-disorder symptoms were related, our findings suggest they are not the same constructs. Increased sluggish cognitive tempo is related to more difficulties with executive function and increased depression, but not anxiety symptoms. Results demonstrate that sluggish cognitive tempo may pose heightened difficulties for adults with autism spectrum disorder, making it an important construct to continue studying. Considerations for assessment and long-term impacts of sluggish cognitive tempo for adults with autism spectrum disorder are discussed.

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3. Carneiro ACC, Flores EP, da Silva Barros R, de Souza CBA. Evaluating the use of programmed reinforcement in a correction procedure with children diagnosed with autism. Psicologia, reflexao e critica : revista semestral do Departamento de Psicologia da UFRGS. 2019 ; 32(1) : 21.

BACKGROUND : Procedures that reduce errors while learning a repertoire play an important role in Applied Behavior Analysis for people with autism due to the detrimental effects that excessive exposure to error may have on learning. Previous studies have investigated the effects of correction procedures that require active student response after a trial with error. Some intervention manuals recommend against reinforcing responses after correction to prevent the establishment of prompt dependence. This study directly investigated the effect of reinforcement after an active-response correction procedure during tact training in four children with autism. An echoic-to-tact training procedure was used to train tacts. A "no reinforcement after correction" (NRC) condition was compared to a "reinforcement after correction" (RC) condition, using an adapted alternated treatments design. RESULTS : All participants needed less correction trials in RC than in NRC, and considering all 26 sessions in which both training procedures were implemented, participants’ performance was higher with RC than without in 17 sessions and was the same in 3 sessions. CONCLUSIONS : We discuss the effectiveness of reinforcing correct responding after an active-response correction procedure, the absence of prompt dependence, and the implications of better correction procedures for applied settings.

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4. Castellani CA, Arking DE. High-Risk, High-Reward Genetics in ASD. Neuron. 2020 ; 105(3) : 407-10.

In a recent issue of Cell, Satterstrom et al. leverage de novo high-impact variants to identify 102 genes associated with autism spectrum disorder (ASD). Most of these genes have roles in regulation of gene expression or neuronal communication, implicating both developmental and functional changes in ASD.

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5. D’Haene E, Bar-Yaacov R, Bariah I, Vantomme L, Van Loo S, Cobos FA, Verboom K, Eshel R, Alatawna R, Menten B, Birnbaum RY, Vergult S. A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett like characteristics. Hum Mol Genet. 2020.

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6. Girault JB, Swanson MR, Meera SS, Grzadzinski RL, Shen MD, Burrows CA, Wolff JJ, Pandey J, John TS, Estes A, Zwaigenbaum L, Botteron KN, Hazlett HC, Dager SR, Schultz RT, Constantino JN, Piven J. Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months. J Neurodev Disord. 2020 ; 12(1) : 5.

BACKGROUND : Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. METHODS : Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD ; n = 296 discordant). We addressed two aims : (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. RESULTS : Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06 ; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains ; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). CONCLUSIONS : Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.

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7. Ho LKH, Tong VJW, Syn N, Nagarajan N, Tham EH, Tay SK, Shorey S, Tambyah PA, Law ECN. Gut microbiota changes in children with autism spectrum disorder : a systematic review. Gut pathogens. 2020 ; 12 : 6.

Background : As more animal studies start to disentangle pathways linking the gut microbial ecosystem and neurobehavioral traits, human studies have grown rapidly. Many have since investigated the bidirectional communication between the gastrointestinal tract and the central nervous system, specifically on the effects of microbial composition on the brain and development. Methods : Our review at the initial stage aimed to evaluate literature on gut microbial alterations in pediatric neurobehavioral conditions. We searched five literature databases (Embase, PubMed, PsychInfo, Scopus, and Medline) and found 4489 published work. As the mechanisms linking gut microbiota to these conditions are divergent, the scope of this review was narrowed to focus on describing gut dysbiosis in children with autism spectrum disorder (ASD). Results : Among the final 26 articles, there was a lack of consistency in the reported gut microbiome changes across ASD studies, except for distinguishable patterns, within limits, for Prevotella, Firmicutes at the phylum level, Clostridiales clusters including Clostridium perfringens, and Bifidobacterium species. Conclusions : These results were inadequate to confirm a global microbiome change in children with ASD and causality could not be inferred to explain the etiology of the behaviors associated with ASD. Mechanistic studies are needed to elucidate the specific role of the gut microbiome in the pathogenesis of ASD.

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8. Isaev DY, Major S, Murias M, Carpenter KLH, Carlson D, Sapiro G, Dawson G. Relative Average Look Duration and its Association with Neurophysiological Activity in Young Children with Autism Spectrum Disorder. Sci Rep. 2020 ; 10(1) : 1912.

Autism Spectrum Disorder (ASD) is characterized by early attentional differences that often precede the hallmark symptoms of social communication impairments. Development of novel measures of attentional behaviors may lead to earlier identification of children at risk for ASD. In this work, we first introduce a behavioral measure, Relative Average Look Duration (RALD), indicating attentional preference to different stimuli, such as social versus nonsocial stimuli ; and then study its association with neurophysiological activity. We show that (1) ASD and typically developing (TD) children differ in both (absolute) Average Look Duration (ALD) and RALD to stimuli during an EEG experiment, with the most pronounced differences in looking at social stimuli ; and (2) associations between looking behaviors and neurophysiological activity, as measured by EEG, are different for children with ASD versus TD. Even when ASD children show attentional engagement to social content, our results suggest that their underlying brain activity is different than TD children. This study therefore introduces a new measure of social/nonsocial attentional preference in ASD and demonstrates the value of incorporating attentional variables measured simultaneously with EEG into the analysis pipeline.

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9. Kersten M, Coxon K, Lee H, Wilson NJ. "In Their Own Time" : Parents Gently Push Their Autistic Youth Towards Independent Community Mobility and Participation. J Autism Dev Disord. 2020.

Autistic adults have decreased independence in community mobility and driving, which is associated with decreased participation in work, education and community participation. This is the first exploration of the development of community mobility, driving and participation skills over adolescence and emerging adulthood. Interviews with 15 mothers of autistic youth, capable of independence, were qualitatively analysed using grounded theory. Four major themes emerged : mothers gently pushing, teaching, letting go and working towards hopes and dreams. These results suggest earlier intervention across adolescence to address social skills, communication and anxiety in normative community environments, is required for successful development of community mobility and driving skills. Further understanding the critical role of confidence, feeling safe and accepted, could ultimately improve independence.

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10. Lew CH, Groeniger KM, Hanson KL, Cuevas D, Greiner DMZ, Hrvoj-Mihic B, Bellugi U, Schumann CM, Semendeferi K. Serotonergic innervation of the amygdala is increased in autism spectrum disorder and decreased in Williams syndrome. Mol Autism. 2020 ; 11(1) : 12.

BACKGROUND : Williams syndrome (WS) and autism spectrum disorder (ASD) are neurodevelopmental disorders that demonstrate overlapping genetic associations, dichotomous sociobehavioral phenotypes, and dichotomous pathological differences in neuronal distribution in key social brain areas, including the prefrontal cortex and the amygdala. The serotonergic system is critical to many processes underlying neurodevelopment and is additionally an important neuromodulator associated with behavioral variation. The amygdala is heavily innervated by serotonergic projections, suggesting that the serotonergic system is a significant mediator of neuronal activity. Disruptions to the serotonergic system, and atypical structure and function of the amygdala, are implicated in both WS and ASD. METHODS : We quantified the serotonergic axon density in the four major subdivisions of the amygdala in the postmortem brains of individuals diagnosed with ASD and WS and neurotypical (NT) brains. RESULTS : We found opposing directions of change in serotonergic innervation in the two disorders, with ASD displaying an increase in serotonergic axons compared to NT and WS displaying a decrease. Significant differences (p < 0.05) were observed between WS and ASD data sets across multiple amygdala nuclei. LIMITATIONS : This study is limited by the availability of human postmortem tissue. Small sample size is an unavoidable limitation of most postmortem human brain research and particularly postmortem research in rare disorders. CONCLUSIONS : Differential alterations to serotonergic innervation of the amygdala may contribute to differences in sociobehavioral phenotype in WS and ASD. These findings will inform future work identifying targets for future therapeutics in these and other disorders characterized by atypical social behavior.

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11. McBride NM, Weinzimmer SA, La Buissonniere-Ariza V, Schneider SC, Ehrenreich May J, Lewin AB, McGuire JF, Goodman WK, Wood JJ, Storch EA. The Impact of Comorbidity on Cognitive-Behavioral Therapy Response in Youth with Anxiety and Autism Spectrum Disorder. Child Psychiatry Hum Dev. 2020.

The impact of externalizing comorbidity on treatment outcome was examined in 104 youth ages 7-16 (M = 11.09 years) with autism spectrum disorder and primary anxiety/obsessive compulsive disorder who completed modular cognitive behavioral therapy (CBT) for anxiety/OCD. Three comorbidity profiles were utilized for group comparisons : participants with oppositional defiant or conduct disorder with attention-deficit hyperactivity disorder (ODD ; CD ; ADHD ; group EXT, n = 25) ; those without ODD/CD and only ADHD (group ADHD, n = 46) ; and those without externalizing comorbidity (NO-EXT, n = 33). Post-treatment outcomes were measured continuously (Pediatric Anxiety Rating Scale, Clinical Global Impression-Severity) and categorically (treatment response, remission). The ADHD group was four times more likely of being a treatment responder compared to NO-EXT (OR 4.05). Comorbidity group did not impact remission. After controlling for pre-treatment scores, there was a significantly greater reduction of the CGI-S for ADHD versus NO-EXT and EXT versus NO-EXT, but results did not significantly differ for the PARS. Results suggest that a modular CBT approach yields positive impact for treatment outcomes in youth with comorbid externalizing problems, particularly among those with comorbid ADHD.

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12. McFayden T, Jarrett MA, White SW, Scarpa A, Dahiya A, Ollendick TH. Sluggish Cognitive Tempo in Autism Spectrum Disorder, ADHD, and Their Comorbidity : Implications for Impairment. J Clin Child Adolesc Psychol. 2020 : 1-8.

Objective : Sluggish Cognitive Tempo (SCT), characterized by lethargy and daydreaming, has most commonly been studied in community samples and in youth with Attention-Deficit/Hyperactivity Disorder (ADHD). Despite shared neurodevelopmental symptoms with ADHD, few studies have investigated SCT in Autism Spectrum Disorders (ASD). The current study investigated SCT symptoms in youth with ASD, ADHD, and comorbid ASD+ADHD to explore the relations between SCT and global and social impairment.Method : Caregivers of children and adolescents (n = 98 ; ages 6-17) diagnosed with ADHD (n = 46), ASD (n = 28), or ASD+ADHD (n = 24) completed measures of social impairment, SCT, and demographic variables.Results : All three clinical groups demonstrated comparable levels of SCT. Diagnosis and SCT independently contributed to parent-rated social impairment, while SCT and IQ, but not diagnosis, contributed to clinician-rated global functioning. Specifically, having comorbid ASD+ADHD, but not an ASD or ADHD diagnosis alone, significantly predicted greater social impairment.Conclusion : These results extend previous literature investigating SCT in ASD and provide evidence to suggest that SCT is associated with social and global impairment above and beyond the impairment associated with ADHD and/or ASD. These results may have implications for clinical assessment and treatment of ASD and ADHD.

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13. McNaughton KA, Redcay E. Interpersonal Synchrony in Autism. Curr Psychiatry Rep. 2020 ; 22(3) : 12.

PURPOSE OF REVIEW : We review evidence for the presence, quality, and correlates of interpersonal synchrony in autism spectrum disorder (ASD) across four domains : motor, conversational, physiological, and neural. We also propose cognitive and neural mechanisms for the disruption of interpersonal synchrony and investigate synchrony as a mechanism of intervention in ASD. RECENT FINDINGS : Across domains, synchrony is present but reduced or atypical in individuals with ASD during interactions with individuals with typical development (TD). Atypical synchrony may reflect the contribution of both intrapersonal mechanisms, such as atypical motor timing, and interpersonal mechanisms, such as atypical interindividual coupling. Research suggests evidence for synchrony interventions leading to improvements in some aspects of social behavior. Understanding synchrony in ASD has the potential to lead to biomarkers and interventions to support social functioning. However, further research should clarify mechanisms of atypical synchrony in ASD including taking features of the dyad into account.

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14. Paudel R, Raj K, Gupta YK, Singh S. Oxiracetam and Zinc Ameliorates Autism-Like Symptoms in Propionic Acid Model of Rats. Neurotoxicity research. 2020.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by restrictive behaviour, deficit in social skills and interaction. The multifactorial etiology, complex pathophysiology and different combination of symptoms (unusual speech patterns, frequent repetition of phrases) make it difficult to treat. Thus, present study aimed to find the protective effects of oxiracetam alone and in combination with zinc on brain behavioral, biochemical, pro-inflammatory cytokines and neurotransmitters level. Rats were administered with propionic acid (250 mg/kg p.o.) for 3 days and immediately on next day treatment were given with oxiracetam (25, 50 mg/kg i.p), zinc (4 mg/kg) as well as oxiracetam (25 mg/kg i.p) in combination with zinc (4 mg/kg p.o). Behavioral parameters were performed from 22th to 28th day. On 29th day, all the animals were sacrificed by cervical dislocation and the brain was preserved for biochemical (LPO, GSH, nitrite, mitochondrial complex I, IV and cAMP), neuroinflammatory (TNF-alpha, IL-1beta, IL-6) and neurotransmitters (5-HT, GABA, glutamate and acetylcholine) analysis. The propionic acid administration showed memory impairment, restrictive behavior, increased proinflammatory cytokines level, biochemical and neurotransmitters alteration. However, treatment with oxiracetam alone and in combination with zinc significantly attenuated behavioral, biochemical, inflammatory cytokines and restored neurotransmitters level. The finding of present study demonstrated that oxiracetam alone and in combination with zinc afforded superior anti-autistic effect through antioxidant, anti-inflammatory and anti-excitotoxic mechanisms and could serve as attractive strategy in managing autism.

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15. Riley JD, Delahunty C, Alsadah A, Mazzola S, Astbury C. Further evidence of GABRA4 and TOP3B as autism susceptibility genes. European journal of medical genetics. 2020 : 103876.

Chromosomal copy number variants (CNVs) are known contributors to neurodevelopmental conditions such as autism spectrum disorder (ASD). Both array comparative genomic hybridization and next-generation sequencing techniques have led to an increased detection of small CNVs and the identification of many candidate susceptibility genes for ASD. We report familial inheritance of two CNVs that include genes with known involvement in neurodevelopment. These CNVs are found in various combinations among four siblings with autism spectrum disorder, as well as in their neurodevelopmentally normal parents. We describe a 2.4Mb duplication of 4p12 to 4p11 that includes GABRA4 (OMIM : 137141) and other GABA receptor genes, as well as a 246kb deletion at 22q11.22 involving the TOP3B gene (OMIM : 603582). The maternally inherited 4p duplication was detected in three siblings, two of whom also had the paternally inherited 22q11.22 deletion. The fourth sibling only had the 22q11.22 deletion. These CNVs have rarely been reported in the literature. Upon review, a single publication was found describing a similar 4p duplication in three generations of a family with neurodevelopmental and neuropsychiatric disorders, as well as in an unrelated patient with autism (Polan et al., 2014). TOP3B falls within the distal 22q11.22 microdeletion syndrome and has been associated with schizophrenia, neurodevelopmental disorders including epilepsy, and cardiac defects. The identification of this family contributes to the understanding of specific genetic contributors to neurodevelopmental disorders and an emerging phenotype associated with proximal 4p duplication.

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16. Salcedo-Arellano MJ, Hagerman RJ, Martinez-Cerdeno V. Fragile X syndrome : clinical presentation, pathology and treatment. Gaceta medica de Mexico. 2020 ; 156(1) : 60-6.

Fragile X syndrome is the monogenetic condition that produces more cases of autism and intellectual disability. The repetition of CGG triplets (> 200) and their methylation entail the silencing of the FMR1 gene. The FMRP protein (product of the FMR1 gene) interacts with ribosomes by controlling the translation of specific messengers, and its loss causes alterations in synaptic connectivity. Screening for fragile X syndrome is performed by polymerase chain reaction. Current recommendation of the American Academy of Pediatrics is to test individuals with intellectual disability, global developmental retardation or with a family history of presence of the mutation or premutation. Hispanic countries such as Colombia, Chile and Spain report high prevalence of fragile X syndrome and have created fragile X national associations or corporations that seek to bring patients closer to available diagnostic and treatment networks.

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17. Shattuck PT, Garfield T, Roux AM, Rast JE, Anderson K, Hassrick EM, Kuo A. Services for Adults With Autism Spectrum Disorder : a Systems Perspective. Curr Psychiatry Rep. 2020 ; 22(3) : 13.

PURPOSE OF REVIEW : We review original research about services for adults on the autism spectrum published from January 2013 through December 2018. The main aim is to characterize the topical and methodological aspects of research about services. We review research on services related to employment, living in the community, and social participation. We compare our results with those from a similar review published in 2012 to assess progress and identify where new directions in research about services for adults with autism are needed. RECENT FINDINGS : We found the evidence base about services for adults on the autism spectrum remains very small and highly variable in aims and methods. There is wide variability in methods used to define sampling frames and recruit participants. Most studies focus on employment. Almost no studies examine the overall ecosystem of services serving autistic adults. Few studies use a conceptual framework for understanding access to, or improvement of, services. The small size of the extant research coupled with inconsistent quality prevents the accumulation of new knowledge in ways that would significantly inform the improvement of systems of care for the growing population of adults on the autism spectrum.

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18. Zervogianni V, Fletcher-Watson S, Herrera G, Goodwin M, Perez-Fuster P, Brosnan M, Grynszpan O. A framework of evidence-based practice for digital support, co-developed with and for the autism community. Autism. 2020 : 1362361319898331.

LAY ABSTRACT : Digital supports are any type of technologies that have been intentionally developed to improve daily living in some way. A wide array of digital supports (such as apps) have been developed for the autism community specifically, but there is little or no evidence of whether they work or not. This study sought to identify what types of evidence the autistic community valued and wanted to see provided to enable an informed choice to be made regarding digital supports. A consensus was developed between autistic people and their families, practitioners (such as therapists and teachers) as well as researchers, to identify the core aspects of evidence that everyone agreed were useful. In all, 27 people reached agreement on three categories for which evidence is required : reliability, engagement and the effectiveness of the technology. Consensus was also reached on four key sources of evidence for these three categories : hands-on experience, academic sources, expert views and online reviews. The resulting framework allows for any technology to be evaluated for the level of evidence identifying how effective it is. The framework can be used by autistic people, their families, practitioners and researchers to ensure that decisions concerning the provision of support for autistic people is informed by evidence, that is, ’evidence-based practice’.

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