Abstract Background Autism Spectrum Disorder Research Articles

14 Comorbidities Affecting Children with Autism Spectrum Disorder: A Retrospective Chart Review from the Main Referral Site for ASD Evaluation in Manitoba

Abstract Background Autism Spectrum Disorder (ASD) is a developmental disorder characterized by deficits in social interaction/communication, restricted interests and repetitive behaviours. Recent discussions have emerged worldwide regarding a possible “overly-inclusive” diagnosis of ASD, adding heterogeneity around presentation/etiology and comorbidities. Objectives This study aimed to determine the frequency and characteristics of comorbidities among children diagnosed with ASD in Manitoba, and to evaluate differences in presentation between those with and without medical comorbidities. As comorbid neurodevelopmental disorders such as global developmental delay (GDD) and attention-deficit yyperactivity disorder (ADHD) are common in children with ASD, these were not included as “medical comorbidities” and were studied separately. Design/Methods We conducted a retrospective chart review of >2000 electronic charts at the main referral site for children <6 years requiring evaluation for ASD in Manitoba. All children aged 0-5 years diagnosed with ASD at this site between May 2016 to September 2021 were identified. X2 and t test were used to compare groups. Results Of the total of 1858 children identified, 1459 (78%) were male, 252 (13.5%) were born prematurely, 504 (27%) had ≥1 medical comorbidity. Most common medical comorbidities were neurological (12.7%) and allergies/eczema (6.1%). Comorbid GDD was diagnosed in 428 (23%). Age of referral to RCC and age of diagnosis did not differ between groups. Medical comorbidities were more common among preterm children (31% vs. 26%, p:<0.01) and children with comorbid GDD (35% vs. 18.6%, p:<0.01). There was no significant difference in overall presence of medical comorbidities by sex (29.5% vs. 26.6%, p: 0.25); however, girls had a statistically significant higher incidence of neurological comorbidities, e.g. cerebral palsy, epilepsy, hypotonia NYD (16% vs. 12%, p:0.03). Conclusion Results of this study are consistent with previous studies, which note high comorbidity rates among children with ASD. The high rates of associated neurological conditions, GDD, and prematurity add heterogeneity to this group and may relate to the reported “overly-inclusive” diagnosis. This study will be used as a catalyst for guiding further prospective studies in the area.

Quantitative Stool Culture of Candida in Autism Spectrum Disorder Patients

Abstract Background Autism spectrum disorder (ASD) is a category of neurodevelopmental disorders characterized by social and communication impairment and restricted or repetitive behaviors. Aim of the Work to estimate the quantity of Candida in autism spectrum disorder (ASD) patients compared to normal children and to find the association between Candida colony count and severity of ASD. Patients and Methods The study was carried out on 40 children, diagnosed as autism and 40 normal children as control group recruited from Pediatrics and adolescent Psychiatric Clinic at Ain Shams University Pediatrics Hospitals and Main Microbiology lab in Clinical Pathology Department of Ain Shams University. The study was conducted on a wide age group ranging from 3 to 14 years, (mean age of 6.30±2.40 years), Stool sample was collected from each patient in a sterile container, cultured on Sabouraud Dextrose Agar (SDA) and colony count was determined. Identification of isolated Candida species was done using chromogenic media. Results The study revealed statistically significant difference in Candida isolation rate among patient and control group with p-value (p = 0.006). Candida species were isolated from 23 patients (57.5%) and from 10 child in control group (25%), But detected that stool count was nonsignificant in severe autistic group compared to mild to moderate autistic group with p-value more than 0.05 NS. There were 14 patients (60.9%) with C. Albicans; 2 patients (8.7%) C. Glabrata; 6 patients (26.1%) C.Krusie and one patient (4.3%) C. Utilis, among candida species. Conclusion ASD is more common among male than female; ratio about 4:1. The high rate of intestinal colonization by Candida species in ASD children may represent a part of syndrome related to immune system disorders that may play a role in the pathogenesis of ASD. C. albicans was the predominant isolate than other non-Candida albicans species in ASD. The degree of candida colonization represented as quantitative colony count is not related to the severity of CARS among ASD patients.

47 Prevalence of and Factors Associated with Language Impairment in Canadian Children with ASD

Abstract Background Autism Spectrum Disorder (ASD) is a life-long neurodevelopmental disorder affecting 1 in 66 Canadians aged 5-17, and language impairment is a common comorbidity in this population. We aimed to determine the relative prevalence of diagnosed language impairment in children with ASD. We also examined factors associated with language impairment in children with ASD. Objectives 1 – To determine the relative prevalence of language impairment in children diagnosed with ASD. 2 – To identify factors associated with language impairment in children with ASD. Design/Methods Our study sample included 6,862 children aged 0-19 years, assessed for ASD (61% diagnosed with ASD) between 2010-2017 in British Columbia, Canada. ASD was diagnosed by a provincially qualified specialist and the assessment included the use of the Autism Diagnostic Observation Schedule (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R). We also looked for associations between language impairment and gender, age, intellectual disability (ID), family history of language disorders, and attention deficit hyperactivity disorder (ADHD), using chi-square analyses. Results The overall prevalence of language impairment in children diagnosed with ASD (n = 1820, 44%) was similar to those not diagnosed (n = 1199, 44%). There was more mixed receptive/expressive (80% vs 65%) and less expressive only (22% vs 29%) language impairment in children diagnosed with ASD than without. Looking only at the children diagnosed with ASD, there was no significant difference when evaluating gender (boys 44%, girls 41%; p = 0.094), but younger age was positively associated with language impairment (age <6y 53%, ≥6y 24%; p < 0.01). Increasing severity of ID was negatively associated with language impairment (mild: 44%, p = 0.911; moderate: 33%, p = 0.001; severe: 21%, p < 0.001). Family history of speech language disorder was positively associated with language impairment (no family history 12%, family history 20%; p < 0.01). Presence of comorbid ADHD was negatively associated with language impairment (no ADHD 47%, ADHD 28%; p < 0.01). Conclusion In children who have been referred for an ASD assessment, the prevalence of language impairment is similar in those with and without ASD. Children with ASD are more likely to be diagnosed with mixed language impairment than expressive only language impairment, although this difference may in part be due to challenges in fully assessing a child with ASD’s receptive language.

49 Implementation of a Sensory Toolkit in the Emergency Department for Children with Autism Spectrum Disorder

Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive patterns of behaviour, interests, or activities. Children with ASD frequently visit the emergency department (ED), and present more for primary care-related issues and other non-emergent reasons than children without ASD. Visiting the ED can be challenging and stressful for children with ASD, their caregivers, and the healthcare professionals caring for them. Sensory Toolkits are a collection of sensory items that can help to distract and calm children, including during times of stress. We hypothesized that a Sensory Toolkit will improve the experience of children with ASD and their families in our ED. Objectives The primary objective of this study was to evaluate the effect of a Sensory Toolkit on the experience of children with ASD and their families visiting a tertiary-care hospital ED. Design/Methods After ethical approval was obtained, a pre-implementation survey was conducted on parents of children with ASD about prior experiences in the ED and their interest in a Sensory Toolkit. A Sensory Toolkit specific to children with ASD was developed through literature review and in consultation with families of children with ASD. The Sensory Toolkit, which included a light wand, squeeze ball, push-pop bubble toy, and other items, was launched in a tertiary-care hospital ED in June 2021 with 50 Toolkits. A post-implementation survey was conducted to explore parents’ experiences of their child using the Sensory Toolkit in the ED and to obtain feedback to help improve the Toolkit. Results In the pre-implementation survey, 80% (32/40) of parents felt that a Sensory Toolkit would improve the experience of children with ASD in the ED. Post-implementation, 100% (12/12; response rate ~25% from 50 Toolkits) of parents felt that the Sensory Toolkit was helpful for their child. Parents reported that the Sensory Toolkit was “AMAZING” and “A really great idea, thank you!”. Feedback provided regarding improvements that could be made to the Sensory Toolkit was highly patient-specific and often contradictory. One parent suggested more items to chew on while another parent suggested elimination of the chewable items and one parent loved the light up toy while another suggested to remove it. Conclusion The Sensory Toolkit contributes positively to the experience of children with ASD and their families in a tertiary-care hospital ED. This study will help inform improvement of the Sensory Toolkit in the ED, including consideration of more specialized Sensory Toolkits to meet individual patient needs. Given the success in the ED, the Sensory Toolkit could be expanded into other areas of the tertiary-care hospital and beyond.

Comparison of the Effects of Movement-Based Interventions Delivered Face-to-face Versus Via Telehealth on Restricted and Repetitive Behaviors of Children With Autism Spectrum Disorder

Background Autism spectrum disorder (ASD) is the most common pediatric neurodevelopmental disorder with a prevalence of 1 in every 44 children. Children with ASD exhibit social communication and behavioral impairments including poor verbal and nonverbal communication and heightened frequencies of repetitive and maladaptive behaviors (RBs). Objective Our randomized controlled trial compares face-to-face (F2F) versus telehealth-based intervention delivery for three types of interventions: two whole-body gross motor interventions and a conventional seated play (SP) intervention on RBs in children with ASD. Methods A total of 45 children with a confirmed diagnosis of ASD (aged 5-14 years) were recruited, matched on age bands and level of functioning, and randomly assigned to 1 of the 3 intervention groups, creative movement (CM), general movement (GM), or SP. Sessions were 1 to 1.5 hours long and were conducted with the child twice a week over 8 weeks by an expert clinician, adult confederate, and the caregiver. We coded videos of early and late training sessions for 3 types of RBs: sensory, stereotyped, and negative. Frequencies per standard time were calculated for RBs across early and late sessions. Results Data from a subset of 39 children suggest that there was a significant reduction in total RBs from an early to a late session in the CM group (early: mean 34.8, SE 5.0; late: mean 24.7, SE 3.9; P=.01) but not in the GM (early: mean 34.8, SE 5.0; late: mean 24.7, SE 3.9; P=.01) and SP groups (early: mean 14.6, SE 3.1; late: mean 15.2, SE 4.0; P=.79). The reduction in total RBs in the CM group did not differ significantly between children seen F2F (mean 14.2, SE 4.4) versus via telehealth (mean 5.3, SE 3.8; P=.20). The CM group specifically reduced frequencies of sensory (early: mean 10.7, SE 1.8; late: mean 6.2, SE 1.9; P=.03) and negative (early: mean 10.7, SE 2.6; late: mean 7.4, SE 2.3; P=.01) behaviors. Similar to the trends reported above, the reductions were not significantly different for children seen F2F and via telehealth (sensory F2F: mean 5.1, SE 1.8; sensory telehealth: mean 4.7, SE 3.7; P=.92; negative F2F: mean 2.6, SE 1.3; negative telehealth mean 3.7, SE 2.1; P=.66). Conclusions CM activities involving music and movement are novel contexts and lead to higher frequencies of RBs at baseline compared to conventional SP activities in children with ASD. However, training children reduced the frequencies of RBs, especially negative and sensory behaviors. No improvements were found in the GM or SP groups. Although our sample size was limited, preliminary data suggests similar trends for improvement in children seen F2F versus via telehealth. Telehealth-based training seems to be a viable mode of intervention delivery for families with difficulties accessing in-person care. Conflicts of Interest None declared.

Effects of Novel, Whole-body Movement–Based Interventions on Locomotor Skills in Children With Autism Spectrum Disorder: Randomized Controlled Trial Comparing Face-to-face and Telehealth Modes of Intervention Delivery

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder limiting a child’s motor performance to a level half their chronological age. Due to COVID-19, there has been growing research on the use of telehealth-based interventions in the care of children with ASD. Objective Based on previous research from our lab, this study assessed the effects of 2 novel, whole-body movement interventions (creative movement and general movement) compared to a standard-of-care, seated play intervention using a randomized controlled trial design. Interventions were delivered either face-to-face (F2F) or via telehealth (TH) across all groups. Methods In total, 45 children with ASD (aged 5-14 years) participated in a 10-week study. Children were matched on age and level of functioning and then randomly assigned to the Play (creative movement), Move (general movement), or Standard-of-care control (seated play) group (n=15 per group) to receive 8 weeks of intervention F2F or via TH. The interventions were provided twice a week for 8 weeks, with each session lasting for around 1 to 1.5 hours. The locomotor subtest of the Test of Gross Motor Development was administered at pretest and posttest to assess the form and accuracy of locomotor skills (running, galloping, hopping, leaping, horizontal jump, sliding, and skipping). Results Improvements were seen in overall standard scores in the Play (pretest: mean 6.53, SE 0.97; posttest: mean 8.60, SE 0.97; P<.05) and Move groups (pretest: mean 6.07, SE 0.96; posttest: mean 8.07, SE 0.92; P<.05) but not in the Create group (pretest: mean 6.13, SE 0.88; posttest: mean 6.80, SE 0.87; P.05). Specifically, 75% of children seen via TH and 57.1% of children seen F2F improved in the Play group, and 89% of children seen via TH and 50% of children seen F2F improved in the Move group. Conclusions Our pilot data suggest that TH is a viable option for movement intervention delivery and can be used to promote locomotor skills in children with ASD. Broadly, movement-based interventions must be included in the plan of care for children with ASD, given their significant challenges with movement performance.

A convergent structure-function substrate of cognitive imbalances in autism.

Autism spectrum disorder (ASD) is a common neurodevelopmental diagnosis showing substantial phenotypic heterogeneity. A leading example can be found in verbal and nonverbal cognitive skills, which vary from elevated to impaired compared with neurotypical individuals. Moreover, deficits in verbal profiles often coexist with normal or superior performance in the nonverbal domain. To study brain substrates underlying cognitive imbalance in ASD, we capitalized categorical and dimensional IQ profiling as well as multimodal neuroimaging. IQ analyses revealed a marked verbal to nonverbal IQ imbalance in ASD across 2 datasets (Dataset-1: 155 ASD, 151 controls; Dataset-2: 270 ASD, 490 controls). Neuroimaging analysis in Dataset-1 revealed a structure-function substrate of cognitive imbalance, characterized by atypical cortical thickening and altered functional integration of language networks alongside sensory and higher cognitive areas. Although verbal and nonverbal intelligence have been considered as specifiers unrelated to autism diagnosis, our results indicate that intelligence disparities are accentuated in ASD and reflected by a consistent structure-function substrate affecting multiple brain networks. Our findings motivate the incorporation of cognitive imbalances in future autism research, which may help to parse the phenotypic heterogeneity and inform intervention-oriented subtyping in ASD.

Program evaluation of a pilot mobile developmental outreach clinic for autism spectrum disorder in Ontario

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing prevalence worldwide. Early identification of ASD through developmental screening is critical for early intervention and improved behavioural outcomes in children. However due to long wait times, delays in diagnosis continue to occur, particularly among minority populations who are faced with existing barriers in access to care. A novel Mobile Developmental Outreach Clinic (M-DOC) was implemented to deliver culturally sensitive screening and assessment practices to increase access to developmental health services, reduce wait times in diagnoses, and aid in equitable access to intervention programs among vulnerable populations in Ontario.MethodsThis study applied two evaluation frameworks (process and outcome evaluation) to determine whether the delivery model was implemented as intended, and if the program achieved its targeted goals. A mixed-methods design was undertaken to address the study objectives.ResultsBetween September 2018–February 2020, M-DOC reached 227 families with developmental health concerns for their child, while successfully targeting the intended population and achieving its goals. The mean age of the child-in-need at intake was 31.6 months (SD 9.9), and 70% of the sample were male. The program’s success was attributed to the use of cultural liaisons to break cultural and linguistic barriers, the creation of multiple points of access into the diagnosis pathway, and delivery of educational workshops in local communities to raise awareness and knowledge of autism spectrum disorder.ConclusionsThe findings underscore the need for community-based intervention programs that focus on cultural barriers to accessing health services. The model of delivery of the M-DOC programs highlights the opportunity for other programs to adopt a similar mobile outreach clinic approach as a means to increase access to services, particularly in targeting hard-to-reach and vulnerable populations.

Personality as a mediator of autistic traits and internalizing symptoms in two community samples

BackgroundAutism spectrum disorder (ASD) is characterized by deficits in social functioning and is comorbid with internalizing disorders and symptoms. While personality is associated with these symptoms and social functioning in non-ASD samples, its role mediating the relationship between ASD traits and internalizing symptoms is not clear.MethodsWe studied the mediating effect of personality on the correlations between ASD traits and internalizing symptoms (i.e., depression, anxiety, stress) in two samples. Additionally, we explored the moderating effect of gender. Analyses were applied to a small (Study 1; N = 101) undergraduate sample. A broader sample recruited via an online crowdsourcing platform (Study 2; N = 371) was used to validate the results.ResultsStudy 1’s mediation analyses revealed that neuroticism was the only significant mediator. Study 2 replicated these results by finding extraversion to be an additional mediator for anxiety and extraversion, openness, and agreeableness as additional mediators for stress. Moderation analyses revealed that gender was never a significant moderator.ConclusionsThese results support the effects of personality on the relationship between autism traits and internalizing symptoms. Future research should explore these effects in clinical samples to better understand the role of personality in symptomatology and the need to address it as part of intervention.

The impact of schizotypy on quality of life among adults with autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) and schizotypal personality disorder can be difficult to distinguish. Deficits in social relationships and social interaction, present in both conditions, are known to impair quality of life. The aim of the present study was to investigate if schizotypal symptoms affect quality of life among adults diagnosed with autism spectrum disorder and to study the association between schizotypy and autistic traits among them.MethodsParticipants diagnosed with autism spectrum disorder (n = 110) completed questionnaires exploring schizotypy (Schizotypal Personality Questionnaire – Brief Revised (SPQ-BR)), autistic traits (The Ritvo Autism, Asperger Diagnostic Scale-Revised Screen 14 items), anxiety and depression (The Hospital Anxiety and Depression scale) and quality of life (Brunnsviken Brief Quality of Life Scale and the European quality of life index version 5D).ResultsSchizotypy was found to be associated with anxiety, depressive and autistic symptoms, and poor quality of life. Although schizotypy was a predictor for impaired quality of life, this relationship was mediated by symptoms of anxiety and depression, plausibly inherent to autism. Autistic traits were positively associated with all higher order constructs of the SPQ-BR, i.e. positive and negative schizotypy, disorganization and social anxiety, as well as with poor quality of life.ConclusionsThere is considerable overlap between schizotypy and autism that needs to be considered in research. Prominent schizotypal traits in people with ASD may constitute an endophenotype coinciding with a particularly poor quality of life.Trial registrationClinicalTrials.gov identifier: NCT03570372: Internet-based Treatment for Adults with Autism Spectrum Disorder (MILAS).

Tools for early screening of autism spectrum disorders in primary health care \u2013 a scoping review

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder that manifests itself in early childhood. Early diagnosis of these disorders allows for the initiation of early therapy, which is crucial for the child's further functioning in society.ObjectivesThis review aims to gather and present the existing ASD screening tools that can be used in primary care and adapted to different countries conditions linguistically and culturally.Eligibility criteriaWe searched for English-language publications on ASD screening tools for children aged 0–3 years suitable for use in primary care (i.e. free, requiring no additional training or qualifications).Sources of evidenceFour databases were explored to find English studies on ASD screening tools intended for the rapid assessment of children aged 0–3.Charting methodsThe information sought (specific features of the questionnaires relevant to primary health care workers, psychometric and diagnostic values of a given cultural adaptation of screening tools, and the linguistic and cultural changes made) were extracted and collected to create profiles of these tools.ResultsWe found 81 studies which met inclusion criteria and underwent full data extraction. Three additional data sources were included. These allowed to create 75 profiles of adaptations for 26 different screening tools and collect data on their psychometric values and characteristic features.ConclusionsThe results of our study indicate the availability of several diagnostic tools for early ASD screening in primary care setting concordant culturally and linguistically with a given population. They could be an effective method of accelerating the diagnostic process and starting personalized therapy faster. However, most tools have significant limitations – some are only available for research purposes, while others do not have scientific evidence to prove their effectiveness.

Integrin \u03b23 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice

BackgroundAutism spectrum disorder (ASD) is characterized by repetitive behaviors, deficits in communication, and overall impaired social interaction. Of all the integrin subunit mutations, mutations in integrin β3 (Itgb3) may be the most closely associated with ASD. Integrin β3 is required for normal structural plasticity of dendrites and synapses specifically in excitatory cortical and hippocampal circuitry. However, the behavioral consequences of Itgb3 function in the forebrain have not been assessed. We tested the hypothesis that behaviors that are typically abnormal in ASD—such as self-grooming and sociability behaviors—are disrupted with conditional Itgb3 loss of function in forebrain circuitry in male and female mice.MethodsWe generated male and female conditional knockouts (cKO) and conditional heterozygotes (cHET) of Itgb3 in excitatory neurons and glia that were derived from Emx1-expressing forebrain cells during development. We used several different assays to determine whether male and female cKO and cHET mice have repetitive self-grooming behaviors, anxiety-like behaviors, abnormal locomotion, compulsive-like behaviors, or abnormal social behaviors, when compared to male and female wildtype (WT) mice.ResultsOur findings indicate that only self-grooming and sociability are altered in cKO, but not cHET or WT mice, suggesting that Itgb3 is specifically required in forebrain Emx1-expressing cells for normal repetitive self-grooming and social behaviors. Furthermore, in cKO (but not cHET or WT), we observed an interaction effect for sex and self-grooming environment and an interaction effect for sex and sociability test chamber.LimitationsWhile this study demonstrated a role for forebrain Itgb3 in specific repetitive and social behaviors, it was unable to determine whether forebrain Itgb3 is required for a preference for social novelty, whether cHET are haploinsufficient with respect to repetitive self-grooming and social behaviors, or the nature of the interaction effect for sex and environment/chamber in affected behaviors of cKO.ConclusionsTogether, these findings strengthen the idea that Itgb3 has a specific role in shaping forebrain circuitry that is relevant to endophenotypes of autism spectrum disorder.

Autism Spectrum Disorder Managed with Individualised Homoeopathic Medicine—Analysis of 20 Cases

Abstract Background Autism spectrum disorder (ASD) is an umbrella term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours. There is a dramatic increase in prevalence of ASD in the past few decades. Autism is a potentially lifelong impairing disorder usually managed with complementary therapies, symptomatic behavioural, sensory integration therapies and medical treatments. As there are currently no specific medicines that can address core disabilities of ASD, there is a desperate need to explore new interventions in ASD. Objectives The aim of this study is to assess the effectiveness of homoeopathic medicines in the usual care setting, i.e. regular OPD, for the management of ASD using Autism Treatment Evaluation Checklist (ATEC). Materials and Methods The present study is a case series analysis of 20 cases diagnosed as ASD and evaluated with ATEC in the outpatient unit of Department of Psychiatry, National Homoeopathy Research Institute in Mental Health. Individualised homoeopathic medicines were prescribed based on classical homoeopathic principles. Wilcoxon signed-rank test was used to compare ATEC scores at baseline to end of 12 months. Results The median baseline ATEC score of 110.0 (116.0–94.5) reduced to 33.5 (61.75–25.0) at p < 0.001, with an effect size of 0.88. There was statistically significant difference in all domains of speech language communication, sociability, sensory/cognitive awareness and health/physical/behaviour when compared from baseline to end of 12 months. Calcarea carbonica, Calcarea phosphorica, Carcinosinum, Mercurius solubilis, Natrum muriaticum, Silicea, Theridion, Tuberculinum, Zincum metallicum etc. were commonly indicated homoeopathic medicines. Conclusion Individualised Homoeopathic medicines are effective in the management of ASD. Well planned, methodically rigorous research is warranted to corroborate the evidence.

Pediatric Tuina in children with autism spectrum disorder: a study protocol for a randomized controlled trial

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by repetitive stereotypical behavior and communication deficits. Currently, it lacks a specific clinical treatment method. Pediatric Tuina is a recent therapy in traditional Chinese medicine (TCM) and has been used to treat children with ASD. Nonetheless, it remains uncommon given the lack of large-scale evidence-based medical studies. This study aims to compare the efficacy of Tuina and conventional treatment in children with ASD.MethodsEligible children will be randomly assigned to either the pediatric Tuina plus conventional treatment group or to the conventional treatment alone group based on a random table at a ratio of 1:1. The effectiveness of the Tuina intervention for ASD will be evaluated by a third-party organization. The pre- and post-intervention scores on the Childhood Autism Rating Scale comprised the primary outcome, whereas pre- and post-intervention scores on the Autism Treatment Evaluation Checklist were the secondary outcomes to assess improvement in symptoms. Baseline values of the participants will be determined at the time of registration. Outcomes will be evaluated after the 30th treatment session. The follow-up period will last for 6 months after treatment.DiscussionThis study will evaluate the effectiveness and safety of Tuina in the treatment of ASD. The results of this study could provide reliable evidence to improve the management of patients with ASD.Trial registrationChinese Clinical Trial Registry (CHICTR), ChiCTR2000040452. Registered on 28 November 2020.

Health care providers\u2019 awareness on medical management of children with autism spectrum disorder: cross-sectional study in Russia

BackgroundAutism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD, and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD.MethodsThis online survey research study evaluated the awareness and experience of students/residents (n = 247) and physicians (n = 100) in the medical management of children with ASD. It also gathered the views and experiences of caregivers to children with ASD (n = 158), all based in Russia.ResultsWe have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on results from online surveys completed by students/residents, non-psychiatric physicians, and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified. Possible problem solving solutions within medical practice were proposed.ConclusionsThe results from this study should be considered when implementing measures to improve healthcare practices, and when developing models for effective medical management, due to start not only in Russia but also in a number of other countries.

Internalization of stigma among parents of children with autism spectrum disorder in Nigeria: a mixed method study

BackgroundAutism Spectrum disorder (ASD) has uniquely stigmatizing aspects because children with ASD have no physical markers of their condition. Parents are usually blamed and judgment from others is often internalized (felt stigma).AimThis study was conducted to determine knowledge about ASD, negative experiences (enacted stigma), internalization of stigma (felt or self stigma) and its correlates among parents of children with ASD in Lagos, Nigeria.MethodsThis was a cross-sectional study of 230 parents in Lagos, Nigeria employing mixed-method data collection methods. Quantitative data were collected using a structured interviewer-administered questionnaire and analyzed with Epi- Info™ version 7.0 statistical package. Data were summarized with proportions, mean and standard deviation. Chi square and Spearman’s correlation tests were done, and the level of significance was pre-determined at 5% (p < 0.05). In-depth interviews were also conducted among six parents to further explore the topic. The interviews were analyzed narratively.ResultsThe proportion of mothers and fathers were 175 (76.1%) and 55 (23.9%) respectively. The mean age of respondents was 42 ± 8.5 years. Overall knowledge of ASD was very poor as only 3(1.3%) had good knowledge. Overall, 122(53%) usually had negative experience of parenting a child with ASD (enacted stigma), mothers (17.1%) more than fathers (9.1%). Majority 192(83.5%) internalized stigma. There was a low–moderate correlation between ‘enacted’ stigma and ‘internalized’ stigma (ρ- 0.400, p < 0.001). From in-depth interviews, many parents revealed that their child’s condition had negative effects on the family. Many also recounted negative experience of stigma.ConclusionOverall, parents of children with ASD had poor knowledge of the condition. Majority internalized stigma and this increases with negative treatment from others. Parents should be properly educated about ASD. Community-based education to increase awareness about ASD in addition to encouraging people to show empathy and reduce stigmatizing behaviour towards parents of children with ASD are recommended.

Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism.

BackgroundAutism spectrum disorders (ASD) are a set of neurodevelopmental disorders marked by a lack of social interaction, restrictive interests, and repetitive behaviors. There is a paucity of pharmacological treatments to reduce core ASD symptoms. Various lines of evidence indicate that reduced brain muscarinic cholinergic receptor activity may contribute to an ASD phenotype.MethodsThe present experiments examined whether the partial M1 muscarinic receptor agonist, 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A), alleviates behavioral flexibility deficits and/or stereotyped motor behaviors in the BTBR mouse model of autism. Behavioral flexibility was tested using a reversal learning test. Stereotyped motor behaviors were measured by eliciting digging behavior after removal of nesting material in a home cage and by measuring repetitive grooming.ResultsCDD-0102A (0.2 and 0.6 mg/kg but not 1.2 mg/kg) injected prior to reversal learning attenuated a deficit in BTBR mice but did not affect performance in B6 mice. Acute CDD-0102A treatment (1.2 and 3 mg/kg) reduced self-grooming in BTBR mice and reduced digging behavior in B6 and BTBR mice. The M1 muscarinic receptor antagonist VU0255035 (3 mg/kg) blocked the effect of CDD-0102A on grooming behavior. Chronic treatment with CDD-0102A (1.2 mg/kg) attenuated self-grooming and digging behavior in BTBR mice. Direct CDD-0102A infusions (1 µg) into the dorsal striatum reduced elevated digging behavior in BTBR mice. In contrast, CDD-0102A injections in the frontal cortex were not effective.ConclusionsThe results suggest that treatment with a partial M1 muscarinic receptor agonist may reduce repetitive behaviors and restricted interests in autism in part by stimulating striatal M1 muscarinic receptors.

Looking for consistency in an uncertain world: test-retest reliability of neurophysiological and behavioral readouts in autism

BackgroundAutism spectrum disorders (ASD) are associated with altered sensory processing and perception. Scalp recordings of electrical brain activity time-locked to sensory events (event-related potentials; ERPs) provide precise information on the time-course of related altered neural activity, and can be used to model the cortical loci of the underlying neural networks. Establishing the test-retest reliability of these sensory brain responses in ASD is critical to their use as biomarkers of neural dysfunction in this population.MethodsEEG and behavioral data were acquired from 33 children diagnosed with ASD aged 6–9.4 years old, while they performed a child-friendly task at two different time-points, separated by an average of 5.2 months. In two blocked conditions, participants responded to the occurrence of an auditory target that was either preceded or not by repeating visual stimuli. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability of measures of sensory (auditory and visual) ERPs and performance, for the two experimental conditions. To assess the degree of reliability of the variability of responses within individuals, this analysis was performed on the variance of the measurements, in addition to their means. This yielded a total of 24 measures for which ICCs were calculated.ResultsThe data yielded significant good ICC values for 10 of the 24 measurements. These spanned across behavioral and ERPs data, experimental conditions, and mean as well as variance measures. Measures of the visual evoked responses accounted for a disproportionately large number of the significant ICCs; follow-up analyses suggested that the contribution of a greater number of trials to the visual compared to the auditory ERP partially accounted for this.ConclusionsThis analysis reveals that sensory ERPs and related behavior can be highly reliable across multiple measurement time-points in ASD. The data further suggest that the inter-trial and inter-participant variability reported in the ASD literature likely represents replicable individual participant neural processing differences. The stability of these neuronal readouts supports their use as biomarkers in clinical and translational studies on ASD. Given the minimum interval between test/retest sessions across our cohort, we also conclude that for the tested age-range of ~ 6 to 9.4 years, these reliability measures are valid for at least a 3-month interval. Limitations related to EEG task demands and study length in the context of a clinical trial are considered.

Neuroprotective effects of Clitoria ternatea L. against propionic acid-induced behavior and memory impairment in autistic rat model

BackgroundAutism spectrum disorder is primarily characterized by complex behavioral and altered memory as a consequence of neuronal development abnormalities. The treatment of autism is highly challenging because of the lack of knowledge about its exact etiopathology. In the Ayurvedic system of medicine, there are group of plants named ‘Medhya drugs' because of their ability to improve brain- and neuron-related activities like learning and memory. Clitoria ternatea L. is one of the listed ‘Medhya drugs’ which have been proved for its memory enhancement effects; in the present study, the ethanolic root extract of Clitoria ternatea L. was evaluated for its neuroprotective ability against propionic acid-induced memory and behavior impairments in an autistic rat model. The variation in behavior and memory were investigated by utilizing different procedures like rat elevated plus maze and novel object recognition test. In vitro assays for the estimations of glutamate and serotonin were also performed in isolated rat brain tissue homogenate.ResultsThe object recognition and elevated plus maze test were showed the promising effects of Clitoria ternatea L. ethanolic root extract against the propionic acid-induced autism. In this study, the propionic acid infused rats (Group II) fail to recognize and explore the novel object compared to Group I (infused with phosphate-buffered saline) animals; extract treatment at two different doses (250 mg/kg and 500 mg/kg) (Groups III & IV, respectively) prevented these damage significantly (p < 0.001) so that extract-treated groups showed significant improvement in novel object recognition in a dose-dependent manner. Similarly, the effect of extract treatment on learning and memory of rats was investigated using transfer latency as a parameter for acquisition and retention of memory process on elevated plus maze; this further proved the memory enhancement ability of Clitoria ternatea L. Extract treatment also significantly reduced the concentration of different neurotransmitters like serotonin and glutamate in rat brain homogenate (Groups III &IV) in a dose-dependent manner as compared with the Group II.ConclusionThe ethanolic root extract of Clitoria ternatea L. proved to be effective against propionic acid-induced memory and behavior impairments in an autistic rat model.

GAT-LI: a graph attention network based learning and interpreting method for functional brain network classification

BackgroundAutism spectrum disorders (ASD) imply a spectrum of symptoms rather than a single phenotype. ASD could affect brain connectivity at different degree based on the severity of the symptom. Given their excellent learning capability, graph neural networks (GNN) methods have recently been used to uncover functional connectivity patterns and biological mechanisms in neuropsychiatric disorders, such as ASD. However, there remain challenges to develop an accurate GNN learning model and understand how specific decisions of these graph models are made in brain network analysis.ResultsIn this paper, we propose a graph attention network based learning and interpreting method, namely GAT-LI, which learns to classify functional brain networks of ASD individuals versus healthy controls (HC), and interprets the learned graph model with feature importance. Specifically, GAT-LI includes a graph learning stage and an interpreting stage. First, in the graph learning stage, a new graph attention network model, namely GAT2, uses graph attention layers to learn the node representation, and a novel attention pooling layer to obtain the graph representation for functional brain network classification. We experimentally compared GAT2 model’s performance on the ABIDE I database from 1035 subjects against the classification performances of other well-known models, and the results showed that the GAT2 model achieved the best classification performance. We experimentally compared the influence of different construction methods of brain networks in GAT2 model. We also used a larger synthetic graph dataset with 4000 samples to validate the utility and power of GAT2 model. Second, in the interpreting stage, we used GNNExplainer to interpret learned GAT2 model with feature importance. We experimentally compared GNNExplainer with two well-known interpretation methods including Saliency Map and DeepLIFT to interpret the learned model, and the results showed GNNExplainer achieved the best interpretation performance. We further used the interpretation method to identify the features that contributed most in classifying ASD versus HC.ConclusionWe propose a two-stage learning and interpreting method GAT-LI to classify functional brain networks and interpret the feature importance in the graph model. The method should also be useful in the classification and interpretation tasks for graph data from other biomedical scenarios.