Pubmed du 24/06/20

mercredi 24 juin 2020

1. Baker E, Veytsman E, Martin AM, Blacher J, Stavropoulos KKM. Increased Neural Reward Responsivity in Adolescents with ASD after Social Skills Intervention. Brain Sci ;2020 (Jun 24) ;10(6)

The reward system has been implicated as a potential neural mechanism underlying social-communication deficits in individuals with autism spectrum disorder (ASD). However, it remains unclear whether the neural reward system in ASD is sensitive to behavioral interventions. The current study measured the reward positivity (RewP) in response to social and nonsocial stimuli in seven adolescents with ASD before and after participation in the Program for the Education and Enrichment of Relational Skills (PEERS(®)) intervention. This study also included seven neurotypical adolescents who were tested at two time points but did not receive intervention. We examined the RewP across the course of a task by comparing brain activity during the first versus second half of trials to understand patterns of responsivity over time. Improvements in social skills and decreased social-communication impairments for teens with ASD were observed after PEERS(®). Event-related potential (ERP) results suggested increased reward sensitivity during the first half of trials in the ASD group after intervention. Adolescents with ASD who exhibited less reward-related brain activity before intervention demonstrated the greatest behavioral benefits from the intervention. These findings have implications for how neuroscience can be used as an objective outcome measure before and after intervention in ASD.

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2. Ben Said M, Robel L, Chaste P, Perisse D, Oreve MJ, Zylberberg P, Philippe A, Jousselme C, Lacoste S, Speranza M, Hafsa I, Cisse F, Cherqaoui Z, Jais JP. TEDIS, a Comprehensive Data Model for In-Depth Clinical Assessment of Patients Affected with Neuro-Developmental Disorders Including Autism. Stud Health Technol Inform ;2020 (Jun 16) ;270:1401-1402.

TEDIS, an information system dedicated to patients affected with neuro-developmental disorders including autism, focuses on patient data generated during in-depth clinical assessment in nine expert centers in Ile-de-France region. Long term partnership involving methodologists and domain experts is necessary to support quality data production and analyses and to guarantee quality data and information governance in a domain characterized by frequent evolutions in clinical assessment instruments and in diagnostic criteria and classification.

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3. Bilgen I, Guvercin G, Rekik I. Machine Learning Methods for Brain Network Classification : Application to Autism Diagnosis using Cortical Morphological Networks. J Neurosci Methods ;2020 (Jun 20):108799.

BACKGROUND : Autism spectrum disorder (ASD) affects the brain connectivity at different levels. Nonetheless, non-invasively distinguishing such effects using magnetic resonance imaging (MRI) remains very challenging to machine learning diagnostic frameworks due to ASD heterogeneity. So far, existing network neuroscience works mainly focused on functional (derived from functional MRI) and structural (derived from diffusion MRI) brain connectivity, which might not directly capture relational morphological changes between brain regions. Indeed, machine learning (ML) studies for ASD diagnosis using morphological brain networks derived from conventional T1-weighted MRI are very scarce. NEW METHOD : To fill this gap, we leverage crowdsourcing by organizing a Kaggle competition to build a pool of machine learning pipelines for neurological disorder diagnosis with application to ASD diagnosis using cortical morphological networks derived from T1-weighted MRI. RESULTS : During the competition, participants were provided with a training dataset and only allowed to check their performance on a public test data. The final evaluation was performed on both public and hidden test datasets based on accuracy, sensitivity, and specificity metrics. Teams were ranked using each performance metric separately and the final ranking was determined based on the mean of all rankings. The first-ranked team achieved 70% accuracy, 72.5% sensitivity, and 67.5% specificity, where the second-ranked team achieved 63.8%, 62.5%, 65% respectively. CONCLUSION : Leveraging participants to design ML diagnostic methods within a competitive machine learning setting has allowed the exploration and benchmarking of wide spectrum of ML methods for ASD diagnosis using cortical morphological networks.

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4. Bowrin P, Iqbal U. Strengthening Behavior and Social Functioning Among Persons with Autism Spectrum Conditions Using Artificial Intelligence and Behavioral Activation : Protocol for the Well-Being and Health for Loved onEs with ASD (WHOLE) Psychosocial Pilot Randomized Controlled Trial. Stud Health Technol Inform ;2020 (Jun 16) ;270:1399-1400.

Although a proportion of families and communities in low resource settings continue to provide care to loved ones with autism spectrum conditions, many of the affected persons remain undiagnosed and without access to proven therapies due to high treatment cost and cultural pressures, in particular. Use of conversational agents on mobile phones in combination with behavior activation home care may provide an innovative, culturally appropriate and affordable platform for strengthening behavior and social functioning outcomes, in addition to an opportunity for participation of the persons with autism spectrum conditions in the intervention development process. We aim to assess the effectiveness of an intervention that incorporates artificial intelligence conversational agent technologies and behavioral activation therapy techniques.

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5. Çelikkol Sadıç Ç, Bilgiç A, Kılınç İ, Oflaz MB, Baysal T. Evaluation of Appetite-Regulating Hormones ın Young Children with Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Jun 24)

This study aimed to investigate the role of leptin, ghrelin, neuropeptide Y, and nesfatin-1 in young children with autism spectrum disorder (ASD). A total of 44 children with ASD and 44 healthy controls aged 18-60 months were included. Plasma levels of hormones were measured using commercial enzyme-linked immunosorbent assay kits. Plasma leptin and ghrelin levels were significantly higher in the ASD group than in the control group. However, no significant difference for plasma neuropeptide Y and nesfatin-1 levels was detected between the groups. No relation was found between the severity of ASD symptoms, severity of eating problems, and plasma levels of hormones. Leptin and ghrelin may play a potential role in the pathogenesis of ASD.

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6. Chatterjee M, Manyakov NV, Bangerter A, Kaliukhovich DA, Jagannatha S, Ness S, Pandina G. Learning Scan Paths of Eye Movement in Autism Spectrum Disorder. Stud Health Technol Inform ;2020 (Jun 16) ;270:287-291.

Eye tracking studies have demonstrated deficits in attention in individuals with Autism Spectrum Disorder (ASD) for a range of different social attention-based tasks. Here we examined social attention skills in a large sample of ASD participants (n = 120), using eye tracking data from a social information processing task, and compared them with a typically developing (TD) group (n = 35). Assuming eye movement parameters are random variables generated by an underlying stochastic process, we modeled the fixation sequences of participants in ASD and TD groups with a Hidden Markov Model. The Regions of Interests (ROIs), modeled as hidden states, corresponded to the true ROIs with a prediction accuracy of >90% for each group. The transition between ROIs revealed bias towards a specific area in the scene in ASD group, which deviated from the TD group. Objective time-dynamic measures of gaze patterns can potentially serve as useful endpoints in ASD diagnosis. Clinical Trial Registration : NCT02299700.

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7. Colombo-Dougovito AM, Blagrave AJ, Healy S. A grounded theory of adoption and maintenance of physical activity among autistic adults. Autism ;2020 (Jun 24):1362361320932444.

BACKGROUND : Although a growing body of literature has explored the physical activity experiences from the perspective of children on the autism spectrum, the perspective of autistic adults remains largely unheard. Due to this absence of perspective, there exists limited knowledge of the appropriateness and generalizability of current models and theories of physical activity for this population. METHODS : A constructivist grounded theory study was conducted to explore the experiences of adoption and maintenance of physical activity from the direct perspective of autistic adults. Autistic adults (n = 23) from the United States and the United Kingdom were recruited. RESULTS : A total of 29 codes emerged from the coding process. These codes were formed into four broad categories : (1) individual attributes ; (2) environmental factors ; (3) social relationships ; and (4) social experiences. The interconnectedness of these four categories was explored. CONCLUSIONS : The findings and presented model highlight the importance of building successful experiences for young children on the autism spectrum, so that they are more likely to continue physical activity into their adult life. Furthermore, findings emphasize the importance of creating noncompetitive, sensory-friendly physical activity experiences for autistic adults that offer flexibility in social engagement. LAY ABSTRACT : Little is known about how autistic adults experience physical activity. To begin to change this, we interviewed 23 autistic adults from the United State and the United Kingdom about their past and current experiences of physical activity participation. The interviewees told us about how their physical activity experiences were highly influenced by their individual strengths, the setting in which the activity took place, the presence of people to support their physical activities, and the sensory experiences they had while in physical activity. Through these interviews, we were able to create a model that represented the physical activity experiences discussed. Based on the model that emerged from this study, we recommend physical activity opportunities are made available that are noncompetitive, sensory-friendly, and that allow for participants to socialize as they prefer.

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8. Fantasia V, Markant DB, Valeri G, Perri N, Ruggeri A. Memory enhancements from active control of learning in children with autism spectrum disorder. Autism ;2020 (Jun 24):1362361320931244.

Research with adults and typically developing children has shown that being able to actively control their learning experience, that is, to decide what to learn, when, and at what pace, can boost learning in a variety of contexts. In particular, previous research has shown a robust advantage of active control for episodic memory as compared with conditions lacking this control. In this article, we explore the potential of active control to improve learning of 6- to 12-year-old children diagnosed with autism spectrum disorder. We presented them with a simple memory game on a touchscreen tablet, in which children were asked to recall as many of the presented objects as possible. For half of the objects, children could decide the order and pacing of study (active condition) ; for the other half, they passively observed the study decisions of a previous participant (yoked condition). We found that recognition memory was more accurate when children could actively control the order, pace, and frequency of the study experience, even after a week-long delay. We discuss how teachers and educators might promote active learning approaches in educational and pedagogical applications to support inclusive learning.

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9. Gerasimenko M, Cherepanov SM, Furuhara K, Lopatina O, Salmina AB, Shabalova AA, Tsuji C, Yokoyama S, Ishihara K, Brenner C, Higashida H. Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder. Sci Rep ;2020 (Jun 22) ;10(1):10035.

Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, a sister protein of CD38, has been considered a candidate mediator for the production and release of OT and its social engagement and anti-anxiety functions. However, the limited expression of CD157 in the adult mouse brain undermined confidence that CD157 is an authentic and/or actionable molecular participant in OT-dependent social behaviour. Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD). NAD is the substrate for the CD157- and CD38-dependent production of cADPR. Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR- and OT-forming deficits to overcome these deficits and function more normally.

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10. He WC, Zhang XJ, Zhang YQ, Zhang WJ. Elevated serum neurofilament light chain in children autism spectrum disorder : a case control study. Neurotoxicology ;2020 (Jun 24)

OBJECTIVE : We aimed to assess serum neurofilament light chain (sNfL) levels in autism spectrum disorder (ASD) and to investigate whether they are related to the severity of disease. METHODS : The cohorts consisted of 166 children aged 3-8 (83 children diagnosed with ASD and 83 children with typically-developing). sNfL were analyzed using Single Molecule Array (Simoa) technology. ASD symptom severity was assessed according to the Chinese version of the Childhood Autism Rating Scale (CARS) score. RESULTS : The mean age of those included ASD was 5.1 years (standard deviations [S.D.] : 1.7) and 78.3% were boys. The mean (SD) sNfL concentrations were significantly (P < 0.001) higher in ASD than in TP children (10.2[5.0] pg/ml and 7.1[3.2]pg/ml). For each 1 pg/ml increase of sNfL, the risk of ASD would increase by 19% (with the OR (unadjusted) of 1.19 [95% CI 1.10-1.29], P < 0.001) and 11% (with the OR (adjusted) of 1.11 [1.03-1.23], P < 0.001), respectively. sNfL concentrations in children with severe ASD were higher than in those children with mild-to-moderate ASD (12.4[5.1] pg/ml vs. 8.3[4.2]pg/ml ; P < 0.001). Among ASD cases, each 1 pg/ml increase of sNfL is associated with 20% higher unadjusted or 11% higher adjusted odds, respectively, of severe (vs. mild-to-moderate) ASD. CONCLUSIONS : The data showed that sNfL was elevated in ASD and related to symptom severity, suggesting that sNfL may play a role in ASD progression.

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11. Kato R, Machida A, Nomoto K, Kang G, Hiramoto T, Tanigaki K, Mogi K, Hiroi N, Kikusui T. Maternal approach behaviors toward neonatal calls are impaired by mother’s experiences of raising pups with a risk gene variant for autism. Dev Psychobiol ;2020 (Jun 23)

How the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with a Tbx1 heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce maternal approach behaviors in C57BL6/J mothers. Here, we tested how maternal approach behaviors induced by wild-type and HT USVs are influenced by the mother’s experience in raising pups of these two genotypes. The results showed that wild-type USVs were effective in inducing maternal approach behaviors when mothers raised wild-type but not HT pups. The USVs of HT pups were ineffective regardless of whether mothers raised HT or wild-type pups. However, the sequence structure of pup USVs had no effect on the general, non-directional incentive motivation of maternal behaviors. Our data show how the mother’s experience with a pup with a genetic risk for ASD alters the intrinsic incentive values of USV sequences in maternal approach behaviors.

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12. Landes SD, Turk MA, Formica MK, McDonald KE, Stevens JD. COVID-19 outcomes among people with intellectual and developmental disability living in residential group homes in New York State. Disabil Health J ;2020 (Jun 24):100969.

BACKGROUND : People with intellectual and developmental disabilities (IDD) may be at higher risk of severe outcomes from COVID-19. OBJECTIVE : To describe COVID-19 outcomes among people with IDD living in residential groups homes in the state of New York and the general population of New York State. METHODS : Data for people with IDD are from a coalition of organizations providing over half of the residential services for the state of New York, and from the New York State Department of Health. Analysis describes COVID-19 case rates, case-fatality, and mortality among people with IDD living in residential group homes and New York State through May 28, 2020. RESULTS : People with IDD living in residential group homes were at greater risk of severe COVID-19 outcomes : case rates - 7,841 per 100,000 for people with IDD compared to 1,910 for New York State ; case-fatality - 15.0% for people with IDD compared to 7.9% for New York State ; and mortality rate - 1,175 per 100,000 for people with IDD compared to 151 per 100,000 for New York State. Differences in cases and mortality rate were confirmed across regions of the state, but case-fatality rate was only higher for people with IDD in and around the New York City region. CONCLUSIONS : COVID-19 appears to present a greater risk to people with IDD, especially those living in congregate settings. A full understanding of the severity of this risk will not be possible until US states begin publicly sharing all relevant data they have on COVID-19 outcomes among this population.

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13. Liao X, Li Y. Genetic associations between voltage-gated calcium channels and autism spectrum disorder : a systematic review. Mol Brain ;2020 (Jun 22) ;13(1):96.

OBJECTIVES : The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD). METHODS : A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions. RESULTS : From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca(2+) pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD. CONCLUSIONS : Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype.

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14. Lin BD, Colas F, Nijman IJ, Medic J, Brands W, Parr JR, van Eijk KR, Klauck SM, Chiocchetti AG, Freitag CM, Maestrini E, Bacchelli E, Coon H, Vicente A, Oliveira G, Pagnamenta AT, Gallagher L, Ennis S, Anney R, Bourgeron T, Luykx JJ, Vorstman J. The role of rare compound heterozygous events in autism spectrum disorder. Transl Psychiatry ;2020 (Jun 22) ;10(1):204.

The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X(2) = 6.69, p = 0.0097). After filtering for those variants predicted to be most deleterious, we observed 21 of such variants in probands versus 8 in their deletion-transmitting parents (X(2) = 5.82, p = 0.016). Finally, cumulative CADD scores conferred by these variants were significantly higher in probands than in deletion-transmitting parents (burden test, β = 0.13 ; p = 1.0 × 10(-)(5)). Our findings suggest that the compound heterozygosity described in the current study may be one of several mechanisms explaining variable penetrance of CNVs with known pathogenicity for ASD.

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15. Martin-Kenny N, Bérubé NG. Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice. J Neurodev Disord ;2020 (Jun 24) ;12(1):17.

BACKGROUND : Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours. METHODS : Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak’s multiple comparison test or unpaired Student’s t tests as indicated. RESULTS : The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination ; however, these changes did not correlate with social deficits. CONCLUSION : The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.

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16. Pari E, Cozzi F, Rodocanachi Roidi ML, Grange F, Toshimori K, Ripamonti E. Parenting girls with Rett syndrome : An investigation on self-perceived levels of stress. J Appl Res Intellect Disabil ;2020 (Jun 23)

BACKGROUND : Although lives of parents of girls with Rett syndrome (RTT) are centred on the process of care, in the current literature their perceived levels of stress have been rarely investigated. METHODS : We analysed levels of stress in a sample of 79 fathers and mothers parenting girls with RTT, who were required to compile the Parenting Stress Index (PSI) questionnaire. RESULTS : We found clinical levels of stress in about 39% of fathers, as compared with 44% of the mothers. Severity of RTT, but not other factors such as the genetic domain, presence of epilepsy or scoliosis, predicted Total Stress scores in both fathers’ subsample and mothers’ subsample. A cumulative effect of caring, that is association of higher levels of stress with longer process of care, did also emerge from estimation of smoothing splines. CONCLUSIONS : Fathers’ resources should be taken more into account, especially in the rehabilitation and socialization process of adults with RTT.

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17. Smile SC. Supporting children with autism spectrum disorder in the face of the COVID-19 pandemic. Cmaj ;2020 (May 25) ;192(21):E587.

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18. Yavuz-Kodat E, Reynaud E, Geoffray MM, Limousin N, Franco P, Bonnet-Brilhault F, Bourgin P, Schroder CM. Disturbances of Continuous Sleep and Circadian Rhythms Account for Behavioral Difficulties in Children with Autism Spectrum Disorder. J Clin Med ;2020 (Jun 24) ;9(6)

Sleep disorders are among the most common comorbidities in children with Autism Spectrum Disorder (ASD), and subjectively defined sleep disturbances have been related to ASD symptom severity. However, no study has investigated the differential impact of objectively measured sleep and circadian rhythm disturbances on behavioral difficulties in this population. Fifty-two children with ASD aged 3-10 years underwent assessments of sleep and circadian rest-activity rhythms objectively with actigraphy and subjectively with the Children’s Sleep Habits Questionnaire. Behavioral difficulties were assessed using the ABC-C. Group comparison analyses were used to compare sleep and circadian rhythm parameters of children with higher and lower behavioral difficulties and dominance analysis to rank predictors and address multicollinearity. Children with high irritability had a shorter continuous sleep period compared to those with lower irritability (-60 min, p = 0.04), as well as those with high stereotypic behaviors compared to children with less stereotypies (-75 min, p = 0.006). Objective circadian and sleep disturbances accounted together for, respectively, 17%, 18% and 36% of the variance in social withdrawal, irritability and stereotypic behaviors. The identification of both sleep and circadian rhythm disturbances as explanatory factors for behavioral difficulties warrants their inclusion in the existing behavioral management strategies for children with ASD.

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19. Zebolsky A, Vos D, Soares N. Awareness of genetic testing for children with autism spectrum disorder among caregivers in an autism support group. J Community Genet ;2020 (Jun 24)

Recent discoveries have improved our understanding of the complex genetic mechanisms underlying autism spectrum disorder (ASD). Despite current guidelines, genetic testing for children with ASD is largely underutilized. This has been attributed to a lack of public awareness regarding genetic testing. The role that autism support groups play in this awareness has not been previously described. A web-based survey was developed and distributed through a community support group to assess the awareness and utilization of genetic testing among caregivers for children with ASD. A total of 138 caregivers responded in total. Only 53.6% were aware that genetic testing exists for ASD. Genetic testing was completed in 17.4% of respondents. Rates of awareness were similar across demographic factors including race, family income, education level, and urban, suburban, or rural residence. This supports low awareness as a key factor in the underutilization of genetic testing for ASD, even among members in an organized autism support group. Targeting public awareness through these organizations may be a promising approach for improving the utilization of genetic testing in ASD.

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