Pubmed du 04/08/22
1. Special Issue Announcement: Insights in the Field of Autism and Neurodevelopmental Disorders. ACS Pharmacol Transl Sci;2022 (Aug 12);5(8):518-519.
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2. Amaral DG, Nordahl CW. Amygdala Involvement in Autism: Early Postnatal Changes, But What Are the Behavioral Consequences?. Am J Psychiatry;2022 (Aug);179(8):522-524.
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3. Ambarchi Z, Boulton KA, Thapa R, Thomas EE, DeMayo MM, Sasson NJ, Hickie IB, Guastella AJ. Evidence of a reduced role for circumscribed interests in the social attention patterns of children with Autism Spectrum Disorder. J Autism Dev Disord;2022 (Aug 4)
Reduced social attention is characteristic of Autism Spectrum Disorder (ASD). It has been suggested to result from an early onset and excessive influence of circumscribed interests (CIs) on gaze behaviour, compared to typically developing (TYP) individuals. To date, these findings have been mixed. The current eye-tracking study utilised a visual preference paradigm to investigate the influence of CI versus non-CI objects on attention patterns in children with ASD (aged 3-12 years, n = 37) and their age-matched TYP peers (n = 30). Compared to TYP, social and object attention was reduced in the ASD group irrespective of the presence of CIs. Results suggest a reduced role for CIs and extend recent evidence of atypical attention patterns across social and non-social domains in ASD.
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4. Bin-Khattaf RM, Alonazi MA, Al-Dbass AM, Almnaizel AT, Aloudah HS, Soliman DA, El-Ansary AK. Probiotic Ameliorating Effects of Altered GABA/Glutamate Signaling in a Rodent Model of Autism. Metabolites;2022 (Aug 4);12(8)
Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, such as marked impairment in verbal and nonverbal communication, social skills, and cognition. Excitatory/inhibitory (E/I) imbalances have been recorded as an etiological mechanism of ASD. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, is known to be much lower in both patients and rodent models of ASD. We propose correcting GABA signaling as a therapeutic strategy for ASD. In this study, 40 young male western Albino rats, 3-4 weeks in age, weighing about 60-70 g, were used. The animals were randomly assigned into six experimental groups, each including eight rats. Group I served as the control group and was orally administered phosphate-buffered saline. Groups II and III served as rodent models of ASD and were orally administered a neurotoxic dose of propionic acid (PPA). The rats in the three therapeutic groups (IV, V, and IV) received the same doses of PPA, followed by 0.2 g/kg body weight of pure Bifidobacterium infantis, a probiotic mixture of ProtexinR, and pure Lactobacillus bulgaricus, respectively, for 3 weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six groups. Both pure and mixed Lactobacillus and Bifidobacterium were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects mostly involved the correction of oxidative stress, restoration of depleted GABA, and up-regulation of GABA receptor gene expression. Pure Bifidobacterium was the most effective, followed by the mixture of probiotics and finally lactobacillus. In conclusion, Bifidobacteria and lactobacilli can be used independently or in combination as psychobiotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut-brain axis.
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5. Carson L, Parlatini V, Safa T, Baig B, Shetty H, Phillips-Owen J, Prasad V, Downs J. The association between early childhood onset epilepsy and attention-deficit hyperactivity disorder (ADHD) in 3237 children and adolescents with Autism Spectrum Disorder (ASD): a historical longitudinal cohort data linkage study. Eur Child Adolesc Psychiatry;2022 (Aug 4)
Children and young people with Autism Spectrum Disorder (ASD) have an increased risk of comorbidities, such as epilepsy and Attention-Deficit/Hyperactivity Disorder (ADHD). However, little is known about the relationship between early childhood epilepsy (below age 7) and later ADHD diagnosis (at age 7 or above) in ASD. In this historical cohort study, we examined this relationship using an innovative data source, which included linked data from routinely collected acute hospital paediatric records and childhood community and inpatient psychiatric records. In a large sample of children and young people with ASD (N = 3237), we conducted a longitudinal analysis to examine early childhood epilepsy as a risk factor for ADHD diagnosis while adjusting for potential confounders, including socio-demographic characteristics, intellectual disability, family history of epilepsy and associated physical conditions. We found that ASD children and young people diagnosed with early childhood epilepsy had nearly a twofold increase in risk of developing ADHD later in life, an association which persisted after adjusting for potential confounders (adjusted OR = 1.72, CI95% = 1.13-2.62). This study suggests that sensitive monitoring of ADHD symptoms in children with ASD who have a history of childhood epilepsy may be important to promote early detection and treatment. It also highlights how linked electronic health records can be used to examine potential risk factors over time for multimorbidity in neurodevelopmental conditions.
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6. Cooley Coleman JA, Fee T, Bend R, Louie R, Annese F, Stallworth J, Worthington J, Buchanan CB, Everman DB, Skinner S, Friez MJ, Jones JR, Spellicy CJ. Mosaicism of common pathogenic MECP2 variants identified in two males with a clinical diagnosis of Rett syndrome. Am J Med Genet A;2022 (Aug 4)
Rett (RTT) syndrome, a neurodevelopmental disorder caused by pathogenic variation in the MECP2 gene, is characterized by developmental regression, loss of purposeful hand movements, stereotypic hand movements, abnormal gait, and loss of spoken language. Due to the X-linked inheritance pattern, RTT is typically limited to females. Recent studies revealed somatic mosaicism in MECP2 in male patients with RTT-like phenotypes. While detecting mosaic variation using Sanger sequencing is theoretically possible for mosaicism over ~15%-20%, several variables, including efficiency of PCR, background noise, and/or human error, contribute to a low detection rate using this technology. Mosaic variants in two males were detected by next generation sequencing (NGS; Case 1) and by Sanger re-sequencing (Case 2). Both had targeted digital PCR (dPCR) to confirm the variants. In this report, we present two males with classic RTT syndrome in whom we identified pathogenic variation in the MECP2 gene in the mosaic state (c.730C > T (p.Gln244*) in Patient 1 and c.397C > T (p.Arg133Cys) in Patient 2). In addition, estimates and measures of mosaic variant fraction were surprisingly similar between Sanger sequencing, NGS, and dPCR. The mosaic state of these variants contributed to a lengthy diagnostic odyssey for these patients. While NGS and even Sanger sequencing may be viable methods of detecting mosaic variation in DNA or RNA samples, applying targeted dPCR to supplement these sequencing technologies would provide confirmation of somatic mosaicism and mosaic fraction.
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7. Delpire E, Ben-Ari Y. A Wholistic View of How Bumetanide Attenuates Autism Spectrum Disorders. Cells;2022 (Aug 4);11(15)
The specific NKCC1 cotransporter antagonist, bumetanide, attenuates the severity of Autism Spectrum Disorders (ASD), and many neurodevelopmental or neurodegenerative disorders in animal models and clinical trials. However, the pervasive expression of NKCC1 in many cell types throughout the body is thought to challenge the therapeutic efficacy of bumetanide. However, many peripheral functions, including intestinal, metabolic, or vascular, etc., are perturbed in brain disorders contributing to the neurological sequels. Alterations of these functions also increase the incidence of the disorder suggesting complex bidirectional links with the clinical manifestations. We suggest that a more holistic view of ASD and other disorders is warranted to account for the multiple sites impacted by the original intra-uterine insult. From this perspective, large-spectrum active repositioned drugs that act centrally and peripherally might constitute a useful approach to treating these disorders.
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8. El-Ansary A, Al-Onazi M, Alhowikan AM, Alghamdi MA, Al-Ayadhi L. Assessment of a combination of plasma anti-histone autoantibodies and PLA2/PE ratio as potential biomarkers to clinically predict autism spectrum disorders. Sci Rep;2022 (Aug 3);12(1):13359.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficiencies in social interaction and repetitive behaviors. Multiple studies have reported abnormal cell membrane composition and autoimmunity as known mechanisms associated with the etiopathogenesis of ASD. In this study, multiple regression and combined receiver operating characteristic (ROC) curve as statistic tools were done to clarify the relationship between phospholipase A2 and phosphatidylethanolamine (PE) ratio (PLA2/PE) as marker of lipid metabolism and membrane fluidity, and antihistone-autoantibodies as marker of autoimmunity in the etiopathology of ASD. Furthermore, the study intended to define the linear combination that maximizes the partial area under an ROC curve for a panel of markers. Forty five children with ASD and forty age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of antihistone-autoantibodies, and PLA2 were measured in the plasma of both groups. PE was measured using HPLC. Statistical analyses using ROC curves and multiple and logistic regression models were performed. A notable rise in the area under the curve was detected using combined ROC curve models. Additionally, higher specificity and sensitivity of the combined markers were documented. The present study indicates that the measurement of the predictive value of selected biomarkers related to autoimmunity and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the pathophysiological mechanism of ASD and its link with metabolism. This information may enable the early diagnosis and intervention.
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9. Fathabadipour S, Mohammadi Z, Roshani F, Goharbakhsh N, Alizadeh H, Palizgar F, Cumming P, Michel TM, Vafaee MS. The neural effects of oxytocin administration in autism spectrum disorders studied by fMRI: A systematic review. J Psychiatr Res;2022 (Aug 4);154:80-90.
PURPOSE: Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The prosocial effects of OXT acting in the CNS present it as a potential therapeutic agent for the treatment of aspects of autism spectrum disorder (ASD). In this article, we systematically review the functional MRI (fMRI) literature that reports task-state and resting-state fMRI (rsfMRI) studies of the neural effects of single or multiple dose intranasal OXT (IN-OXT) administration in individuals with ASD. METHOD: We searched four databases for relevant documents (PubMed, Web of Science, Scopus, and Google Scholar) using the keywords « autism spectrum disorder », « Asperger Syndrome », « oxytocin », and « fMRI ». Moreover, we made a manual search to assess the quality of our automatic search. The search was confined to English language articles published in the interval February 2013 until March 2021. RESULTS: The search yielded 12 fMRI studies with OXT intervention, including 288 individuals with ASD (age 8-55 years) enrolled in randomized, double-blind, placebo-controlled, parallel designs, within-subject-crossover experimental OXT trials. Studies reporting activation task and rsfMRI were summarized with region of interest (ROI) or whole-brain voxel wise analysis. The systematic review of the 12 studies supported the proposition that IN-OXT administration alters brain activation in individuals with ASD. The effects of IN-OXT interacted with the type of the task and the overall results did not indicate restoration of normal brain activation in ASD signature regions albeit the lack of statistical evidence. CONCLUSION: A large body of evidence consistently indicates that OXT alters activation to fMRI in brain networks of individuals with ASD, but with uncertain implications for alleviation of their social deficits.
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10. Ferguson J, Dounavi K, Craig EA. The Efficacy of Using Telehealth to Coach Parents of Children with Autism Spectrum Disorder on How to Use Naturalistic Teaching to Increase Mands, Tacts and Intraverbals. J Dev Phys Disabil;2022 (Jul 29):1-31.
There is a growing body of evidence supporting the use of telehealth to provide parent training in behaviour analytic interventions and researchers have begun to focus on international demonstrations of this model. The current study assessed the efficacy of a training package focused on naturalistic teaching strategies designed to upskill parents of children with autism spectrum disorder and provide them with ready to use strategies to increase social communication behaviours across verbal operants. Two parent-child dyads were trained to increase mand, tact and intraverbals during play. Parents displayed increases in fidelity for each strategy and viewed the training favourably. Both children showed gains across verbal operants, as captured by a multiple baseline across behaviours design. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10882-022-09859-4.
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11. Haghighat H, Mirzarezaee M, Araabi BN, Khadem A. A sex-dependent computer aided diagnosis system for autism spectrum disorder using connectivity of resting-state fMRI. J Neural Eng;2022 (Aug 3)
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with the main symptoms of social communication disabilities. ASD is more than four times more common among males than females. The diagnosis of ASD is currently a subjective process by experts the same for males and females. Various studies have suggested the use of brain connectivity features for diagnosis of ASD. Also, sex-related biological factors have been shown to play a role in ASD etiology and influence the brain connectivity. Therefore, proposing an accurate computer aided diagnosis system (CADS) for ASD which consider the sex of subjects seems necessary. In this study, we present a sex-dependent connectivity-based CADS for ASD using resting-state functional magnetic resonance imaging (rs-fMRI). The proposed CADS classifies ASD males from normal males, and ASD females from normal females. After data preprocessing, group independent component analysis (GICA) was applied to obtain the resting-state networks (RSNs) followed by applying dual-regression to obtain the time course of each RSN for each subject. Afterwards, functional connectivity (FC) measures of full correlation and partial correlation and effective connectivity (EC) measure of bivariate granger causality were computed between time series of RSNs. To consider the role of sex differences in the classification process, male, female, and mixed groups were taken into account, and feature selection and classification were designed for each sex group separately. At the end, the classification accuracy was computed for each sex group. In the female group, the classification accuracy of 93.3% was obtained using full correlation while in the male group the classification accuracy of 86.7% was achieved using each of full correlation and bivariate granger causality. Also, in the mixed group, the classification accuracy of 83.3% was obtained using full correlation. This supports the importance of considering sex in diagnosing ASD patients from normal controls (NCs).
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12. Honan I, Sharp N, McIntyre S, Smithers-Sheedy H, Balde I, Quinn K, Morgan M, Rothery S, Butchers T, Laugeson EA. Program evaluation of an adapted PEERS® social skills program in young adults with autism spectrum disorder and/or mild intellectual impairment and social skills difficulties. J Eval Clin Pract;2022 (Aug 4)
RATIONALE, AIMS AND OBJECTIVES: Social challenges are common for young adults with autism spectrum disorder (ASD) and/or mild intellectual impairment, yet few evidence-based interventions exist to address these challenges. PEERS®, the Program for the Education and Enrichment of Relational Skills, has been shown to be effective in improving the social skills of young adults with ASD; however, it requires a significant time commitment for parents of young adults. As such, this mixed-methods study aimed to investigate the experiences of young adults, parents and PEERS® social coaches participating in an adapted PEERS® program, and to evaluate its acceptability and efficacy. METHOD: Young adults with ASD and/or mild intellectual impairment participated in a 16-week PEERS® program. Parents and PEERS® social coaches attended fewer, condensed sessions, where they learnt program content to support the young adults’ social skill development at home and in the community. Focus groups were conducted post intervention. Quantitative pre-post assessment using the Social and Emotional Loneliness Scale for Adults, the Test of Young Adult Social Skills Knowledge, and Quality of Socialization Questionnaire-Young Adults was completed by young adults. The Social Responsiveness Scale Second Edition was completed by young adults and their parents. RESULT: Qualitative results revealed that, taken together, young adults, parents and PEERS® social coaches all felt that the adapted PEERS® program was ‘challenging, but worth it’. The program was acceptable with a 93% attendance rate across all sessions. Whilst young adults’ perceptions of their own social functioning did not change post-intervention, their knowledge of social skills content improved significantly (p < 0.05). Parent perceptions of young adults' social responsiveness also improved (p < 0.05). CONCLUSIONS: Social skill knowledge, social responsiveness, and social engagement improved significantly following the completion of the adapted PEERS® program. It was deemed acceptable and worthwhile by young adults, their parents and PEERS® social coaches.
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13. Kalin NH. Neurodevelopmental and Neurodegenerative Illnesses: Autism, Fragile X Syndrome, Parkinson’s Disease, and Dementia. Am J Psychiatry;2022 (Aug);179(8):515-518.
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14. Kohn BH, Vidal P, Chiao R, Pantalone DW, Faja S. Sexual Knowledge, Experiences, and Pragmatic Language in Adults With and Without Autism: Implications for Sex Education. J Autism Dev Disord;2022 (Aug 3):1-17.
Autistic adults have similar levels of desire for sexual and romantic relationships as their non-autistic peers. However, autistic adults are less likely to be in relationships and have less dating experience. We compared sexual knowledge, experiences, and pragmatic language ability in a community sample of young adults with (n = 27, mean age = 22.11) and without autism (n = 122, mean age = 19.47). Receipt of sex education and sexual knowledge did not differ between groups. However, autistic adults had significantly fewer partnered experiences and impaired pragmatic language. Within both groups, pragmatic skill predicted accurate sexual knowledge above and beyond general communication abilities. Findings suggest that sex education for autistic adults must address the social communication component of healthy romantic and sexual relationships.
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15. Leffa DT, Grevet EH, Bau CHD, Schneider M, Ferrazza CP, da Silva RF, Miranda MS, Picon F, Teche SP, Sanches P, Pereira D, Rubia K, Brunoni AR, Camprodon JA, Caumo W, Rohde LA. Transcranial Direct Current Stimulation vs Sham for the Treatment of Inattention in Adults With Attention-Deficit/Hyperactivity Disorder: The TUNED Randomized Clinical Trial. JAMA Psychiatry;2022 (Sep 1);79(9):847-856.
IMPORTANCE: Transcranial direct current stimulation (tDCS) may improve symptoms of inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, previous trials are characterized by small sample sizes, heterogeneous methodologies, and short treatment periods using clinic-based tDCS. OBJECTIVE: To determine the efficacy and safety of home-based tDCS in treating inattention symptoms in adult patients with ADHD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel, sham-controlled clinical trial (tDCS for the Treatment of Inattention Symptoms in Adult Patients With ADHD [TUNED]), conducted from July 2019 through July 2021 in a single-center outpatient academic setting. Of 277 potential participants screened by phone, 150 were assessed for eligibility on site, and 64 were included. Participants were adults with ADHD, inattentive or combined subtype. Exclusion criteria included current stimulant drug treatment, current moderate to severe symptoms of depression or anxiety, diagnosis of bipolar disorder with a manic or depressive episode in the last year, diagnosis of schizophrenia or another psychotic disorder, and diagnosis of autism spectrum disorder; 55 of participants completed follow-up after 4 weeks. INTERVENTIONS: Thirty-minute daily sessions of home-based tDCS for 4 weeks, 2 mA anodal-right and cathodal-left prefrontal stimulation with 35-cm2 carbon electrodes. MAIN OUTCOMES AND MEASURES: Inattentive scores in the clinician-administered version of the Adult ADHD Self-report Scale version 1.1 (CASRS-I). RESULTS: Included in this trial were 64 participants with ADHD (31 [48%] inattentive presentation and 33 [52%] combined presentation), with a mean (SD) age of 38.3 (9.6) years. Thirty participants (47%) were women and 34 (53%) were men. Fifty-five finished the trial. At week 4, the mean (SD) inattention score, as measured with CASRS-I, was 18.88 (5.79) in the active tDCS group and 23.63 (3.97) in the sham tDCS group. Linear mixed-effects models revealed a statistically significant treatment by time interaction for CASRS-I (βinteraction = -3.18; 95% CI, -4.60 to -1.75; P < .001), showing decreased symptoms of inattention in the active tDCS group over the 3 assessments compared to the sham tDCS group. Mild adverse events were more frequent in the active tDCS group, particularly skin redness, headache, and scalp burn. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, daily treatment with a home-based tDCS device over 4 weeks improved attention in adult patients with ADHD who were not taking stimulant medication. Home-based tDCS could be a nonpharmacological alternative for patients with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04003740.
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16. Levine J, Hakim F, Kooy RF, Gozes I. Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living. J Mol Neurosci;2022 (Aug);72(8):1531-1546.
Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate natural history of the syndrome, mothers of two ADNP syndrome boys aged 6 and a half and two adults aged 27 years (man and woman) were subjected to Vineland III questionnaire assessing adaptive behavior. The boys were assessed again about 2 years after the first measurements. The skill measures, presented as standard scores (SS) included domains of communication, daily living, socialization, motor skills and a sum of adaptive behavior composite. The age equivalent (AE) and growth scale values (GSV) encompassing 11 subdomains assess the age level at which the subject’s raw score is found at a norm sample median and the individual temporal progression, respectively. The norm referenced standard scores age-matched, mean 100 ± 15 of the two children showed the lowest outcome in communication (SS: 20-30). Daily living skills presented SS of 50-60, with a possible potential loss of some activities as the child ages, especially in interpersonal relationships with people outside of the immediate family (boy A). In contrast, in socialization, both children were at the SS of 38, with some positive increase to SS of ~ 45 (interpersonal relations with family members and coping skills, depending on the particular individual), 2 years later. Interestingly, there was an apparent large difference in motor skills (gross and fine) at the young age, with subject B showing a relatively higher level of skills (SS: 70), decreasing to subject A level (SS: 40) 2 years later. Together, the adaptive behavior composite suggested a level of SS: 39-48 with B showing a potential increase (SS: 41-44) and A, a substantial decrease (SS: 48-39), suggesting a strong impact of daily living skills. Adults were at SS: 20, which is the lowest possible score. AE showed minor improvements for subject A and B, with all AE values being below 3 years. GSVs for subject A showed some improvement with age, especially in interpersonal, play and leisure, and gross motor subdomains. GSV for subject B showed minor improvements in the various subdomains. Notably, all subjects showed a percentile rank < 1 compared with age-matched norms except for subject B as to motor domain (2(nd) percentile) at the age of 6 years. In summary, the results, especially comparing SS and AEs between childhood and adulthood, implied a continuous deterioration of activities compared to the general population, encompassing a slower developmental process coupled to possible neurodegeneration, strongly supporting a great need for disease modifying medicinal procedures.
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17. Lopez-Espejo MA, Nuñez AC, Ruz M, Saez V, Moscoso OC, Escobar RG. Caregiver-Child Agreement in Health-Related Quality of Life of Autistic Children and Adolescents. J Autism Dev Disord;2022 (Aug 3):1-10.
This study examined the agreement of perceived health-related quality of life (HRQOL) between caregivers and autistic children and adolescents (n = 133, 5-12 years) using the Pediatric Quality of Life Inventory Generic Core Scales, Fourth Edition (PedsQL 4.0). Results reveal good to excellent agreement over this age range across the total, physical, and psychosocial health scales. However, the emotional, social, and school functioning scores demonstrated lower agreement in dyads with children aged 5-7 than in dyads with children aged 8-12 years. Despite these differences in agreement, overall, the PedsQL 4.0 caregiver-module is a reliable instrument for measuring HRQOL in autistic individuals aged 5-12 years.
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18. MacLaughlin C, Booker S, Chatterji S, Hooker JM, Clark L, Müller CE. Special Issue Announcement: Insights in the Field of Autism and Neurodevelopmental Disorders. ACS Chem Neurosci;2022 (Aug 17);13(16):2349-2350.
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19. Marrus N, Koth KA, Hellings JA, McDonald R, Gwynette MF, Muhle R, Lohr WD, Vasa RA. Psychiatry training in autism spectrum disorder and intellectual disability: Ongoing gaps and emerging opportunities. Autism;2022 (Aug 3):13623613221112197.
Children, adolescents, and adults with autism spectrum disorder and intellectual disability experience high rates of co-occurring psychiatric conditions throughout their lifetime. However, there is a shortage of psychiatrists to treat these populations. We evaluated how much education psychiatrists-in-training receive on how to care for individuals with autism spectrum disorder/intellectual disability. We found that in many psychiatry programs, residents receive limited training experiences in autism spectrum disorder/intellectual disability involving lectures and patient contact and that psychiatry program directors would benefit from more resources to strengthen education in autism spectrum disorder/intellectual disability.
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20. McHugh CL, Dozier CL, Diaz de Villegas SC, Kanaman NA. Using synchronous reinforcement to increase mask wearing in adults with intellectual and developmental disabilities. J Appl Behav Anal;2022 (Aug 3)
In 2020 the Centers for Disease Control provided the public with recommendations to slow the spread of COVID-19 by wearing a mask in the community. In the current study, experimenters coached group home staff via telehealth to implement synchronous schedules of reinforcement to increase mask wearing for 5 adults with intellectual and developmental disabilities. Results showed the intervention effectively increased mask wearing for all participants for up to 30 min. Additionally, some participants for whom we assessed generalization of mask wearing demonstrated generalization to various community environments. Furthermore, procedural integrity data suggested staff could be coached via telehealth to implement the intervention, and staff surveys suggested the procedures and coaching were socially valid.
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21. Moxon-Emre I, Ameis S. Infant Brain Signatures of Genetic Liability for Autism: The Critical Need for Longitudinal Research. Am J Psychiatry;2022 (Aug);179(8):525-527.
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22. Pagalan L, Oberlander TF, Hanley GE, Rosella LC, Bickford C, Weikum W, Lanphear N, Lanphear B, Brauer M, van den Bosch M. The association between prenatal greenspace exposure and Autism spectrum disorder, and the potentially mediating role of air pollution reduction: A population-based birth cohort study. Environ Int;2022 (Sep);167:107445.
BACKGROUND: Autism spectrum disorder (ASD) incidence has increased in past decades. ASD etiology remains inconclusive, but research suggests genetic, epigenetic, and environmental contributing factors and likely prenatal origins. Few studies have examined modifiable environmental risk factors for ASD, and far fewer have examined protective exposures. Greenspace has been associated with positive child development, but very limited greenspace research has examined ASD risk or prenatal exposures. Only one ecological study in 2017 has evaluated the association between greenspace and ASD, observing protective benefits. Greenspace may have direct effects on ASD risk and indirect effects by reducing air pollution exposure, a growing suspected ASD risk factor. OBJECTIVES: To measure the association between prenatal greenspace exposure and ASD risk and examine if reduced air pollution levels in areas of higher greenspace mediate this association. METHODS: We linked a population-based birth cohort of all deliveries in Metro Vancouver, Canada, from 2004 to 2009, with follow-up to 2014. Diagnoses were based on Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised instruments. Greenspace was quantified as the average of the annual mean Normalized Difference Vegetation Index (NDVI) within a 250 m buffer of a residential postal code. Air pollutant exposures-particulate matter with a diameter less than 2.5 µm (PM(2.5)), nitric oxide (NO), and nitrogen dioxide (NO(2))-were derived from previously developed and temporally adjusted land use regression models. We estimated air pollutant exposures as the mean concentration per month during pregnancy. We calculated odds ratios (ORs) using logistic regression per NDVI interquartile range (IQR) increase, adjusting for child sex, birth month and year, maternal age and birthplace, and neighborhood-level urbanicity and income. To estimate the health impact of greenspace on ASD at the population level, we used the logistic regression model and marginal standardization to derive risk differences (RDs). Lastly, to quantify the mediating effect of greenspace on ASD risk through air pollution reduction, we used marginal structural models and a potential outcomes framework to calculate marginal risk differences (RDs) to decompose the total effect of greenspace on ASD into natural direct and indirect effects. RESULTS: Of 129,222 births, 1,921 (1.5 %) children were diagnosed with ASD. The adjusted OR for ASD per NDVI IQR (0.12) increase was 0.96 (95 % CI: 0.90, 1.02) in 250 m buffer zones and 0.94 (95 % CI: 0.89, 1.00) in 100 m buffer zones. On the additive scale, the adjusted RDs were null. Natural direct, natural indirect, and total effect RDs were null for PM(2.5), NO, and NO(2) mediation models. CONCLUSION: Prenatal greenspace exposure was associated with reduced odds of ASD, but in the additive scale, this effect was null at the population level. No mediating effect was observed through reduced air pollution, suggesting that air pollution may act as a confounder rather than as a mediator.
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23. Pervin M, Ahmed HU, Hagmayer Y. Effectiveness of interventions for children and adolescents with autism spectrum disorder in high-income vs. lower middle-income countries: An overview of systematic reviews and research papers from LMIC. Front Psychiatry;2022;13:834783.
BACKGROUND: There is a multitude of systematic reviews of interventions for children and adolescents with autism spectrum disorder (ASD). However, most reviews seem to be based on research conducted in High-Income Countries (HIC). Thus, summary findings may not directly apply to Lower Middle-Income Countries (LMIC). Therefore, we conducted a Meta-Review analyzing systematic reviews on the effectiveness of interventions for target outcomes in children and adolescents with ASD to find out whether there are differences in effectiveness between HIC and LMIC and which interventions can be considered evidence-based in LMIC. METHODS: Electronic databases (PsycINFO, PubMed, Cochrane database of systematic reviews) were searched for reviews on interventions for ASD in children and adolescents from January 2011 through December 2021, which included studies not coming from HIC. Systematic reviews with qualitative and quantitative syntheses of findings were included. Two investigators independently assessed studies against predetermined inclusion/exclusion criteria and extracted relevant data including quality and evidence assessments. Evidence for different types of interventions in HIC vs. LMIC was planned to be compared, but none of the reviews assessed potential differences. Therefore, a narrative review of the studies from LMIC was conducted including an assessment of quality and evidence. RESULTS: Thirty-five reviews fulfilled the inclusion criteria. Eleven considered findings from HIC and LMIC. Sixty-nine percent included studies with various research designs; 63% provided a qualitative synthesis of findings; 77% percent assessed the quality of studies; 43% systematically assessed the level of evidence across studies. No review compared evidence from HIC and LMIC. A review of the studies from LMIC found some promising results, but the evidence was not sufficient due to a small number of studies, sometimes poor quality, and small sample sizes. CONCLUSION: Systematic reviews on interventions for children and adolescents with ASD did not look for potential differences in the effectiveness of interventions in HIC and LMIC. Overall, there is very little evidence from LMIC. None of the interventions can be considered evidence-based in LMIC. Hence, additional research and mutually agreed methodological standards are needed to provide a more secure basis for evidence-based treatments in LMIC trying to establish evidence-based practices.
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24. Pokorny FB, Schmitt M, Egger M, Bartl-Pokorny KD, Zhang D, Schuller BW, Marschik PB. Automatic vocalisation-based detection of fragile X syndrome and Rett syndrome. Sci Rep;2022 (Aug 3);12(1):13345.
Fragile X syndrome (FXS) and Rett syndrome (RTT) are developmental disorders currently not diagnosed before toddlerhood. Even though speech-language deficits are among the key symptoms of both conditions, little is known about infant vocalisation acoustics for an automatic earlier identification of affected individuals. To bridge this gap, we applied intelligent audio analysis methodology to a compact dataset of 4454 home-recorded vocalisations of 3 individuals with FXS and 3 individuals with RTT aged 6 to 11 months, as well as 6 age- and gender-matched typically developing controls (TD). On the basis of a standardised set of 88 acoustic features, we trained linear kernel support vector machines to evaluate the feasibility of automatic classification of (a) FXS vs TD, (b) RTT vs TD, (c) atypical development (FXS+RTT) vs TD, and (d) FXS vs RTT vs TD. In paradigms (a)-(c), all infants were correctly classified; in paradigm (d), 9 of 12 were so. Spectral/cepstral and energy-related features were most relevant for classification across all paradigms. Despite the small sample size, this study reveals new insights into early vocalisation characteristics in FXS and RTT, and provides technical underpinnings for a future earlier identification of affected individuals, enabling earlier intervention and family counselling.
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25. Ramappa S, Anderson A, Jung J, Chu R, Cummings KK, Patterson G, Okada NJ, Green SA. An Observed Assessment of Sensory Responsivity in Autism Spectrum Disorders: Associations with Diagnosis, Age, and Parent Report. J Autism Dev Disord;2022 (Aug 4)
Sensory features are common and impairing in autism spectrum disorder (ASD), but there are few observational sensory assessments that are valid across ages. We used the Sensory Processing 3-Dimensional (SP3-D) observed Assessment and parent-reported Inventory to examine sensory responsivity in 41 ASD and 33 typically-developing (TD) youth across 7-17 years. ASD youth had higher and more variable observed and reported sensory responsivity symptoms compared to TD, but the two measures were not correlated. Observed sensory over-responsivity (SOR) and sensory craving (SC) decreased with age in ASD, though SOR remained higher in ASD versus TD through adolescence. Results suggest that in ASD, the SP3-D Assessment can identify SOR through adolescence, and that there is value in integrating multiple sensory measures.
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26. Reis D, Fricke O, Schulte AG, Schmidt P. Is examining children and adolescents with autism spectrum disorders a challenge?-Measurement of Stress Appraisal (SAM) in German dentists with key expertise in paediatric dentistry. PLoS One;2022;17(8):e0271406.
OBJECTIVES: This questionnaire-based validation study investigated if the dental examination of children and adolescents with autism spectrum disorder is viewed by dentists with key expertise in paediatric dentistry as a challenge or a threat in terms of transactional stress theory. The Stress Appraisal Measure (SAM) was used for this purpose and it’s feasibility and validity was examined as a first part of a multi-stage process for validation in dentistry with a sample of German dentists. It has hardly been investigated how the treatment of children and adolescents with a disorder from the autism spectrum is perceived by dentists. METHODS: An online-based survey (39 questions) plus the SAM as an add-on as well as a preceding short story of imagination on the topic (appointment for a dental check-up in a special school) were developed. Via e-mail members of the German Society of Paediatric Dentistry (DGKiZ) received a link which enabled interested members to participate. The majority of the members of the DGKiZ have additional qualifications in the treatment of children and adolescents and further training in the area of special needs care in dentistry. The data analysis was based on the SAM and its subscales. RESULTS: Out of the 1.725 members of DGKiZ 92 participants (11 male, 81 female) fully completed the questionnaire and the SAM. All in all the dentists rated their own psychological and physical stress in course of treating children and adolescents with a disorder from the autism spectrum between less and partly stressful. Although the structure of the SAM could not be fully mapped by means of a factor analysis, the different ratings « challenge » or « threat » could be comprehensibly evaluated after reading the story. The participants rated the situation from the story in general as challenging but not as threatening. Intercorrelations between the subscales of the SAM (e.g threat and centrality) of r = .56 showed that the scales are not clearly independent of one another. According to the transactional stress model, the SAM bases on, stress (perceived stressfulness) arises from appraisal processes (e.g. threat, controllable-by-self) that bring about a comparison between the requirements for the described situation and one’s own possibilities in terms of a person-environment-fit. In the hierarchical regression a variance of R2 = .48 could be explained with all six subscales (appraisal processes) to predict perceived stressfulness of the SAM within a sample of dentists. CONCLUSIONS: Due to the response rate the results of the SAM are not representative for all German dentists, but it offers an insight into topics of special needs dentistry in Germany that have not yet been examined. Overall, the feasibility and validity of the SAM in the context of mapping cognitive appraisal processes and stress could be confirmed. Taking into account the result that the treatment of children and adolescents with autism spectrum disorder is seen as a challenge, it is concluded that there is a need to improve the education of dental students and graduated dentists in Germany in the field of special needs dentistry.
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27. Shevchuk-Hill S, Szczupakiewicz S, Kofner B, Gillespie-Lynch K. Comparing narrative writing of autistic and non-autistic College students. J Autism Dev Disord;2022 (Aug 4)
We compared short stories by autistic (n = 19) and non-autistic (n = 23) university students. We used automated software and content analysis to code students’ stories. We found that writings were more similar than different. However, autistic students’ stories were rated at a higher reading level (p = .013) than non-autistic students’. Autistic students’ stories contained fewer grammatical errors (p = .02) but were less likely to include a climax (p = .026). Autistic students reported more positive writing affect than non-autistic students (p = .026). Higher writing affect was associated with writing highly fictional texts (p = .03) that contained more sentences (p = .005). Findings suggest writing may be a strength for autistic students and opportunities to write creatively may promote positive affect toward writing.
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28. Sreckovic MA, Kenney CK, Wallace M. Autism Training for Law Enforcement Officers: A Scoping Review. J Autism Dev Disord;2022 (Aug 4)
Law enforcement officers are the primary individuals called and who respond to situations of heightened concern. They make split-second observations and decisions based on how best to react to given safety situations and those involved. Characteristics of autism spectrum disorders (ASD), if not properly understood and reacted to, may quickly escalate a law enforcement officer call in a negative way, making autism training for law enforcement officers imperative. To ascertain what is known about autism training for law enforcement officers, a scoping review was conducted. Five studies met final inclusion criteria. The trainees, context and development of the training, evaluation procedures, and training outcomes are synthesized to provide guidance for future training implementation teams. Areas for future research are presented.
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29. Tan BL, Guan FY, Leung IMW, Kee SY, Devilly OZ, Medalia A. A gamified augmented reality vocational training program for adults with intellectual and developmental disabilities: A pilot study on acceptability and effectiveness. Front Psychiatry;2022;13:966080.
OBJECTIVES: The Augmented Reality Games to Enhance Vocational Ability of Patients (REAP) was an augmented reality vocational training program that provided skills training in the context of a psychiatric rehabilitation program. It was implemented over 10 weeks and consisted of gamified augmented reality café training scenarios and bridging group activities to facilitate transfer of learning to the work context. This pilot study aimed to explore the acceptability and effectiveness of the REAP program when carried out with adults with intellectual and developmental disabilities attending work therapy. Its objectives were: (1) to obtain feedback from participants and trainers on their experiences and acceptability of the REAP program and (2) to measure changes in vocational and cognitive skills of participants in the REAP program. MATERIALS AND METHODS: This was a pretest-posttest mixed methods study. 15 adults with intellectual and developmental disabilities attending work therapy in a non-profit organization participated in the REAP program and their vocational trainers were involved in assisting in this program. Feasibility Evaluation Checklist (FEC) and the Neurobehavioral Cognitive Status Exam (Cognistat) were administered at baseline, post-training and eight weeks after training. The participants and their trainers also provided user feedback via semi-structured interviews. RESULTS: Majority of the participants and trainers found the REAP program to be useful and interesting. They also found that the augmented reality games were user-friendly and provided a unique opportunity to acquire new skills. Participants who engaged in this program showed a significant improvement in vocational skills and aspects of cognitive skills, which were maintained eight weeks after training. CONCLUSION: The gamified augmented reality vocational training was feasible and accepted by both adults with intellectual and developmental disabilities and their trainers. When integrated with bridging sessions to facilitate transfer of learning to existing work therapy, participants on the REAP program showed significant improvements in vocational skills and aspects of cognitive skills. Future experimental studies with larger sample size could provide stronger evidence on its effectiveness in improving vocational outcomes.
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30. Tan S, Pan N, Xu X, Li H, Lin L, Chen J, Jin C, Pan S, Jing J, Li X. The association between sugar-sweetened beverages and milk intake with emotional and behavioral problems in children with autism spectrum disorder. Front Nutr;2022;9:927212.
BACKGROUND: Emotional and behavioral problems are common in children with autism spectrum disorder (ASD). It’s still unclear whether children with ASD have abnormal sugar-sweetened beverages (SSBs) and milk intake and whether this abnormality will affect their emotions and behavior remains unclear. The current study aims to investigate the association of SSBs and milk intake with emotional and behavioral problems in children with autism spectrum disorder (ASD). METHODS: 107 children with ASD and 207 typical developing (TD) children aged 6-12 years old were recruited for the study. The frequency of SSBs and milk intake was assessed by a self-designed questionnaire. Emotional and behavioral problems were assessed by Strength and Difficulties Questionnaire (SDQ). Then, the linear regression model was produced to evaluate the association of SSBs and milk intake with emotional and behavioral problems. RESULTS: In the current study, there was no difference in frequency of SSBs intake between children with ASD and TD children (p > 0.05), and children with ASD consumed less milk compared to TD children (p < 0.05). After adjusting sex, age, maternal and paternal education, and monthly family income, we found a significant difference in each subscale score of SDQ in the two groups (p < 0.05). In children with ASD, higher frequent SSBs intake was positively associated with the scores of the emotional problem (p for trend <0.05), and lower frequent milk intake was inversely associated with the scores of prosocial behavior (p for trend <0.05). No interactive effects were found on SSBs and milk intake with emotional and behavioral problems (p for trend > 0.05). CONCLUSION: In children with ASD, frequency of SSBs and milk intake was associated with the emotional problem and prosocial behavior, respectively. Children with ASD should increase the frequency of milk intake and decrease the frequency of SSBs intake.
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31. Vanegas SB, Dueñas AD, Kunze M, Xu Y. Adapting parent-focused interventions for diverse caregivers of children with intellectual and developmental disabilities: Lessons learned during global crises. J Policy Pract Intellect Disabil;2022;na:1-13.
Parent-focused interventions have been designed to provide training and support to caregivers who are essential in achieving positive outcomes for children with intellectual and developmental disabilities (IDD). In 2020, significant crises, including the COVID-19 pandemic and continued racial tensions, profoundly impacted the livelihood of children with IDD and their families. Many ongoing efforts to address disparities among this population were halted temporarily and required further adaptations. Researchers adapted interventions and support to address the disparities impacting children with IDD and their families with limited guidance. We provide a descriptive case analysis of four parent-focused interventions that responded to the global crises to continue serving children with IDD and their families. The four distinct programs were based on applied behavior analysis and naturalistic, developmental-behavioral paradigms that were culturally adapted for families of young children with IDD from diverse cultural and socioeconomic backgrounds. We present the qualitative reports on the challenges and benefits that arose with adapting the four parent-focused interventions for telehealth implementation. We focused specifically on adaptations made in recruitment and retention, instrumentation and measurement, research staff training, and intervention delivery. We synthesize our experience with challenges and solutions in adapting parent-focused interventions for racially/ethnically and socioeconomically diverse children with IDD and their families. We conclude with recommendations for researchers and practitioners on methods for adapting parent-focused interventions to address the significant health disparities that impact racially, ethnically, and socioeconomically diverse children with IDD and their families.
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32. Vitobello A, Mazel B, Lelianova VG, Zangrandi A, Petitto E, Suckling J, Salpietro V, Meyer R, Elbracht M, Kurth I, Eggermann T, Benlaouer O, Lall G, Tonevitsky AG, Scott DA, Chan KM, Rosenfeld JA, Nambot S, Safraou H, Bruel AL, Denommé-Pichon AS, Tran Mau-Them F, Philippe C, Duffourd Y, Guo H, Petersen AK, Granger L, Crunk A, Bayat A, Striano P, Zara F, Scala M, Thomas Q, Delahaye A, de Sainte Agathe JM, Buratti J, Kozlov SV, Faivre L, Thauvin-Robinet C, Ushkaryov Y. ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model. Am J Hum Genet;2022 (Aug 4);109(8):1436-1457.
ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the role of ADGRL1 in human disease has been elusive. Here, we describe ten individuals with variable neurodevelopmental features including developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy, all heterozygous for variants in ADGRL1. In vitro, human ADGRL1 variants expressed in neuroblastoma cells showed faulty ligand-induced regulation of intracellular Ca(2+) influx, consistent with haploinsufficiency. In vivo, Adgrl1 was knocked out in mice and studied on two genetic backgrounds. On a non-permissive background, mice carrying a heterozygous Adgrl1 null allele exhibited neurological and developmental abnormalities, while homozygous mice were non-viable. On a permissive background, knockout animals were also born at sub-Mendelian ratios, but many Adgrl1 null mice survived gestation and reached adulthood. Adgrl1(-/-) mice demonstrated stereotypic behaviors, sexual dysfunction, bimodal extremes of locomotion, augmented startle reflex, and attenuated pre-pulse inhibition, which responded to risperidone. Ex vivo synaptic preparations displayed increased spontaneous exocytosis of dopamine, acetylcholine, and glutamate, but Adgrl1(-/-) neurons formed synapses in vitro poorly. Overall, our findings demonstrate that ADGRL1 haploinsufficiency leads to consistent developmental, neurological, and behavioral abnormalities in mice and humans.
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33. Wang X, Song X, Jin Y, Zhan X, Cao M, Guo X, Liu S, Ou X, Gu T, Jing J, Cai L, Li X. Association between dietary quality and executive functions in school-aged children with autism spectrum disorder. Front Nutr;2022;9:940246.
BACKGROUND: It is well known that children with autism spectrum disorder (ASD) had executive functions deficit. However, it is still unclear whether the poor dietary quality is related to the impairment of executive functions. The current study aimed to explore the association between dietary quality and executive functions in children with ASD. METHODS: A total of 106 children with ASD (7.7 ± 1.3 years) and 207 typically developing (TD) children (7.8 ± 1.3 years) were enrolled from Guangzhou, China. The Chinese version of Behavior Rating Scale of Executive function (BRIEF), the working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), and the Stroop Color-Word Test (SCWT) were used to measure the participant’s executive functions. The food frequency questionnaire (FFQ) was used to collect the dietary intake information, and the Chinese Diet Balance Index (DBI_16) was used to evaluate the dietary quality. Generalized linear models were used to estimate the association between dietary quality and executive functions. RESULTS: In children with ASD, Low Bound Score (LBS) was positively correlated with the working memory subscale score of BRIEF (β = 0.23, 95% CI: 0.02-0.44, P < 0.05), while High Bound Score (HBS) and LBS were positively correlated with the organizable subscale score of BRIEF (β = 0.44, 95% CI: 0.11-0.77, P < 0.01; β = 0.19, 95% CI: 0.01-0.37, P < 0.05). Compared to TD children, children with ASD had a higher proportion of moderate and high levels of insufficient dietary intake (moderate level, 37.7% vs. 23.2%, high level, 4.7% vs. 1.4%) and moderate level of unbalanced dietary intake (36.8% vs.21.3%), higher scores on all subscales of BRIEF (P < 0.01), and lower score on the working memory (81.3 ± 32.3 vs. 104.6 ± 12.5, P < 0.01), while there was no difference on the SCWT. CONCLUSION: Poor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality.