Mild Autism Spectrum Disorder Research Articles

Expression of key molecules of the classical inflammation activation pathway in blood leukocytes of autistic children

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders, whose causes are currently not fully understood. Research suggests that inflammation and changes in immune functions may play an important role in the development of autism. Increased levels of proinflammatory cytokines in the brains of autistic children lead to negative regulation of synaptic plasticity, as well as impaired proliferation and differentiation of neurons through activation of the nuclear factor kappa B (NF-κB) signaling pathway. The purpose of the work is to analyze the levels of mRNA: TLR2, TLR4, MyD88, IκBα, NF-κB p50, NF-κB p65 in peripheral blood leukocytes of children in comparison with the severity of autism spectrum disorders. The study included 126 children aged from 3 to 13 years (the ratio of boys to girls was 4:1): 45 children with typical neurodevelopment, and 81 children with a clinically confirmed diagnosis of autism. According to the Childhood Autism Rating Scale, 51 children had mild to moderate ASD (CARS score: 29-36), and 30 children had severe autism (CARS score: 36-60). The expression of inflammatory signal transduction pathway molecules was determined in peripheral blood leukocytes using real-time polymerase chain reaction with SYBRGreen. To compare the samples, one-way ANOVA and Tukey’s test were used. It was found that in leukocytes of children with severe ASD, the expression of the adapter protein MyD88 and the p65 subunit of the nuclear transcription factor NF-κB was significantly reduced, and the expression of the NF-κB inhibitor, IκBα, was significantly increased, compared to the control group. In leukocytes of children with mild ASD, a decrease in NF-κB p65 expression was found at a trend level. When comparing groups of children with different severity of autism symptoms (mild/severe), no significant differences were found in the levels of mRNA of key signaling molecules of the classical inflammation activation pathway in blood leukocytes. Thus, in the blood leukocytes of children with severe ASD, suppression of the expression of key molecules of the classical inflammation activation pathway (NF-κB) is observed, which leads to a decrease in the expression of pro-inflammatory cytokines: IL-1β, IL-18 and IL-2, against the background of increased expression of key cytokine of Th1 cells – IFNγ.

CONTINUOUS SCORING OF AUTISM SPECTRUM DISORDER PATIENTS BY ANALYZING THEIR EEG SIGNALS

Clinical manifestations and standard psychological tests have been widely used to diagnose autism spectrum disorder (ASD) patients and evaluate their severity level. The gold-standard criterion to diagnose ASD patients is the childhood autism rating scale (CARS), which is a qualitative questionnaire that is filled out through a systematic interview while no physiological test/record is performed to determine this score. To make the diagnosis process quantitative, electroencephalography (EEG) signals have been repeatedly analyzed to differentiate healthy subjects from ASD patients. However, the precise relationship between the abnormal behavior of EEG signals and different ASD severity levels is not well investigated. Here, we use CARS to qualitatively determine the severity level of 14 autistic children, who voluntarily enrolled in our study. We recorded their EEG signals from 19 scalp channels when they were awake in the idle state and elicited three informative features including approximation entropy, multiscale entropy and sample entropy in successive time frames. Among the three measures of entropy, the last one exhibits the highest sensitivity, where its correlation coefficient (CC) exceeds 0.7, on the electrode positions T6 (CC [Formula: see text] 0.74), P4 (CC [Formula: see text] 0.76) and Cz (CC [Formula: see text] 0.75). Results of sample entropy in channels Cz-versus-Pz and P4-versus-FP2 show that a simple K-nearest neighbor classifier can provide 93% classification accuracy among patients with mild, moderate and severe ASD levels. Comparing the proposed method to the conventional ones, we also extracted power spectral density features from the channels but they failed to identify the ASD severity level with an acceptable accuracy.

Validation of the Sinhala version of the Autism Treatment Evaluation Checklist (ATEC)

Background: Autism Spectrum Disorder is a neuro developmental disorder which has a trend in its increasing prevalence globally. Measuring the outcome of intervention will have a great value for parents and clinicians. At present, there are no tools validated in the Sri Lankan setting to assess treatment outcomes in Autism Spectrum Disorder. Autism Treatment Evaluation Checklist (ATEC) is a self-administered questionnaire in Sinhala for parents/caregivers that is a feasible method of evaluating outcome in a busy clinic.Aims: This study was conducted to translate and culturally adapt the ATEC to the Sinhala language and to establish the validity and reliability of the translation to the local setting.Methods: Permission was sought from the developers of the ATEC questionnaire and ethical approval was obtained for the study. Study was conducted in two stages. In the first stage, ATEC was translated using the translation-back translation method. An expert panel produced a pre-final questionnaire which was pre-tested prior to formulating the final Sinhala version of ATEC. The second stage of the study was conducted to establish validity and reliability of Sinhala ATEC questionnaire in the Sri Lankan popu-lation. Content validity was assured in each step of the translation by the expert committee. Construct validity of the Sinhala ATEC questionnaire was assessed by comparing the sample of 119 parent/caregiver filled final version of the Sinhala ATEC score against the Consultant Child and Adolescent Psychiatrist assessment of the same children conducted independently and recorded according to DSM-5 (level 1, 2 or 3). Test-retest reliability was determined by the same parent/caregiver filling the Sinhala ATEC one week later, in a sample of 14 children. Intra-rater reliability was taken by com-paring 18 pairs of parents/caregivers Sinhala ATEC scores for the same child.Results: Sinhala ATEC showed high validity and reliability. Its concurrent validity has a strong positive Pearson correlation of 0.856 with the Consultant Psychiatrist assessment. Correlation was higher in total score and as well as in subscale II- Sociability score of the Sinhala ATEC. Internal consistency was revealed by Cronbach’s alpha 0.778. Cut off points to distinguish mild autism spectrum disorder from the rest taken as “48 or less” with sensitivity 82%, specificity 94% and area under the curve 0.968. Cut off to separate severe autism spectrum disorder from the rest were taken as “76 or more” with sensitivity 84%, specificity 90%and area under the curve 0.971. Reliability tests, intra class correlation was 0.98 and 0.96 for test-retest and intra rater reliability showed high reliability of Sinhala ATEC. For developing burnout in this study population.Conclusions: Translated version of Sinhala ATEC is suitable for the use in the Sri Lankan population as it shows high validity and reliability. However, further studies are recommended in other areas of the country to assess its usefulness across diverse subcultures and clinical settings.

Beyond the Spectrum: Subtype-Specific Molecular Insights into Autism Spectrum Disorder Via Multimodal Data Integration.

Some toddlers with autism spectrum disorder (ASD) have mild social symptoms and developmental improvement in skills, but for others, symptoms and abilities are moderately or even severely affected. Those with profound autism have the most severe social, language, and cognitive symptoms and are at the greatest risk of having a poor developmental outcome. The little that is known about the underlying biology of this important profound autism subtype, points clearly to embryonic dysregulation of proliferation, differentiation and neurogenesis. Because it is essential to gain foundational knowledge of the molecular biology associated with profound, moderate, and mild autism clinical subtypes, we used well-validated, data-driven patient subtyping methods to integrate clinical and molecular data at 1 to 3 years of age in a cohort of 363 ASD and controls representative of the general pediatric population in San Diego County. Clinical data were diagnostic, language, cognitive and adaptive ability scores. Molecular measures were 50 MSigDB Hallmark gene pathway activity scores derived from RNAseq gene expression. Subtyping identified four ASD, typical and mixed diagnostic clusters. 93% of subjects in one cluster were profound autism and 93% in a different cluster were control toddlers; a third cluster was 76% moderate ability ASD; and the last cluster was a mix of mild ASD and control toddlers. Among the four clusters, the profound autism subtype had the most severe social symptoms, language, cognitive, adaptive, social attention eye tracking, social fMRI activation, and age-related decline in abilities, while mild autism toddlers mixed within typical and delayed clusters had mild social symptoms, and neurotypical language, cognitive and adaptive scores that improved with age compared with profound and moderate autism toddlers in other clusters. In profound autism, 7 subtype-specific dysregulated gene pathways were found; they control embryonic proliferation, differentiation, neurogenesis, and DNA repair. To find subtype-common dysregulated pathways, we compared all ASD vs TD and found 17 ASD subtype-common dysregulated pathways. These common pathways showed a severity gradient with the greatest dysregulation in profound and least in mild. Collectively, results raise the new hypothesis that the continuum of ASD heterogeneity is moderated by subtype-common pathways and the distinctive nature of profound autism is driven by the differentially added profound subtype-specific embryonic pathways.

Efficacy of social skills group intervention among children with mild autism spectrum disorder.

Efficacy of social skills group intervention among children with mild autism spectrum disorder.

The Role of Adverse Childhood Experience in the Relationship Between Autism Severity and Early Intervention and Special Education Plan.

The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the impact of adverse childhood experiences (ACEs) on this association. This study used the 2020-2021 National Survey of Children's Health (NSCH) and included 2,537 children aged 3-17 years old who currently have ASD. Multivariable logistic regression, controlling for demographic and family characteristics and health status, was used to explore the association between autism severity and having an early intervention plan. The analysis was stratified by the number of ACEs to explore their role in the association. Children with moderate or severe ASD were more likely to have a special education or early intervention plan than those with mild ASD in the crude and adjusted models. This association continued to be true for children who experienced 1 ACE (aOR: 2.28, 95%CI: 1.09-4.77) but not true for those who experienced no ACEs (aOR: 1.16, 95%CI: 0.70-1.94) and 2 or more ACEs (aOR: 1.84, 95%CI: 0.92-3.69). Results demonstrate that children with moderate or severe autism were more likely to receive early intervention or special education. This association changed depending on the number of ACEs experiences.

Family-Centric Applied Behavior Analysis Promotes Sustained Treatment Utilization and Attainment of Patient Goals.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication difficulties and restricted repetitive behaviors or interests. Applied behavior analysis (ABA) has been shown to significantly improve outcomes for individuals on the autism spectrum. However, challenges regarding access, cost, and provider shortages remain obstacles to treatment delivery. To this end, parents were trained as parent behavior technicians (pBTs), improving access to ABA, and empowering parents to provide ABA treatment in their own homes. We hypothesized that patients diagnosed with severe ASD would achieve the largest gains in overall success rates toward skill acquisition in comparison to patients diagnosed with mild or moderate ASD. Our secondary hypothesis was that patients with comprehensive treatment plans (>25-40 hours/week) would show greater gains in skill acquisition than those with focused treatment plans (less than or equal to 25 hours/week). Methods: This longitudinal, retrospective chart review evaluated data from 243 patients aged two to 18 years who received at least three months of ABA within our pBT treatment delivery model. Patients were stratified by utilization of prescribed ABA treatment, age, ASD severity (per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and treatment plan type (comprehensive vs. focused). Patient outcomes were assessed by examining success rates in acquiring skills, both overall and in specific focus areas (communication, emotional regulation, executive functioning, and social skills). Patients receiving treatment within the pBT model demonstrated significant progress in skill acquisition both overall and within specific focus areas, regardless of cohort stratification. Patients with severe ASD showed greater overall skill acquisition gains than those with mild or moderate ASD. In addition, patients with comprehensive treatment plans showed significantly greater gains than those with focused treatment plans. The pBT model achieved both sustained levels of high treatment utilization and progress toward patient goals. Patients showed significant gains in success rates of skill acquisition both overall and in specific focus areas, regardless of their level of treatment utilization. This study reveals that our pBT model of ABA treatment delivery leads to consistent improvements in communication, emotional regulation, executive functioning, and social skills across patients on the autism spectrum, particularly for those with more severe symptoms and those following comprehensive treatment plans.

EEG findings and clinical severity and quality of life in non-epileptic patients with autism spectrum disorders

ABSTRACT Electroencephalogram (EEG) abnormalities could be seen in up to 60% of non-epileptic children with autism spectrum disorder (ASD). They have been used as biomarkers of ASD severity. The objective of our study is to identify EEG abnormalities in children with different degrees of ASD severity based on the Autism Treatment Evaluation Checklist (ATEC). We also want to assess the quality of life for children with ASD. All of the children underwent at least one hour of sleep-deprived EEG. Forty-five children were enrolled, of whom 42 were male. EEG abnormalities were found in 10 (22.2%) children, predominantly in the bilateral frontal areas. There were no differences in EEG findings among the mild, moderate, and severe ASD groups. The severity of ASD was associated with female sex (p-value = 0.013), ASD with attention deficit hyperactivity disorder (ADHD) (p-value = 0.032), ASD children taking medications (p-value = 0.048), and a lower Pediatric Quality of Life Inventory (PedsQL) (p-value <0.001). Social and emotional domains were the most problematic for health-related quality of life in ASD children, according to parent reports of PedsQL. Further studies with a larger sample size will help to clarify the potential associations between EEG abnormalities and the severity of ASD, as well as the impact on quality of life.

EXPLORING MINDMEND: AN INNOVATIVE MENTAL HEALTH SUPPORT APP FOR AUTISTIC ADOLESCENTS AND THEIR CAREGIVERS

Teenagers with mild autism spectrum disorders (ASD) and those who care for them face difficulties. Conventional mental health therapies frequently ignore culturally specific factors that are crucial to the patient's overall wellness. The paper aims to introduce and evaluate "MindMend" a smartphone software specifically designed for teenagers with mild autism spectrum disorders (ASD) and their caregivers. It focuses on examining the effectiveness of MindMend in reducing caregiver stress and alleviating autism symptoms. Additionally, it emphasises the significance of providing comprehensive support that considers the cultural and religious nuances of the target population. The software includes modules for social skills training, emotion regulation, and cognitive-behavioural therapy. Users may participate in a helpful online community, track their progress, and set goals. Early research demonstrates encouraging outcomes in reducing caregiver stress and autism symptoms. MindMend seeks to be a flexible instrument that enhances mental health while honouring subtleties related to culture and religion. The methodology integrates software development, evidence-based therapeutic approaches, and outcome evaluation. It aims to create a specialised mental health solution for teenagers with mild autism and their caregivers. The approach strongly emphasises addressing their unique challenges and providing comprehensive support. The development of MindMend involves creating an innovative smartphone application that offers specialised content. The paper assesses how well MindMend helps reduce stress for caregivers and alleviate autism symptoms in teenagers with mild ASD. The evaluation likely includes quantitative and qualitative methods to measure the digital system's impact on users' well-being.

Evaluation of the Impact of Screen Time and Parental Play on Children with an Autism Spectrum Disorder in Comparison with Normal Children

Background: There is a decremental trend seen in parental play in recent times, and there is a mounting trend in screen exposure in children. This changing trend in parental play and screen time exposure may affect child social and communication domains.Objective: To assess the impact of screen time and parental play in children with autism spectrum disorder.Methodology: This is a comparative cross sectional study with a sample of 60 children. Thirty children of age group 2-6 years diagnosed with Autism Spectrum Disorder as per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) attending child guidance Clinic, Government Hospital for Mental care were included in the study.The Parental Play Questionnaire assessed parental play in children. The Digital Screen Exposure Questionnaire(DSEQ) evaluated child screen time exposure. The severity of ASD was assessed by using the CARS scale.Results: Out of thirty samples with Autism spectrum disorder (ASD), 60% of children had moderate ASD, while 20% accounted for mild and severe ASD. Nearly 53.3% of ASD children had a frequency of watching smartphones more than 5 times a week with an average duration of more than 2 hours a day. In contrast, in normal children, only 6.7% have such frequency and an average time of watching smartphones less than 1 hour, significant with a p-value of &lt;0.001. Among the ASD group, 80% of children had active physical parent-child play frequency of less than twice a week. In normal children, about 60% had a frequency of parent-child play several times daily.(p-value &lt;0.001). About 66.7% of ASD children never had to pretend play, and 30% had pretend play once a week.Conclusion: The result showed significantly higher screen time exposure and lack of parental play in childrenwith ASD than in normal children. The need of this digital era is mounting concern about reducing screen time exposure and increasing parental play in childhood.

The effect of painting-based art therapy on teacher-child relationship, aggression and social interactions of children with autism spectrum disorder

The purpose of this applied research was to determine the effectiveness of painting-based art therapy on the teacher-child relationship, aggression and social interactions of children with mild autism spectrum disorder. The current research was conducted using a semi-experimental method of pre-test-post-test type with a control group. The statistical population of the research included all the children with autism disorder of the second April Autism Center in Tehran, 30 of whom were selected by the available sampling method and were randomly assigned to two experimental and control groups. To collect information, Nielson's Aggression Questionnaire (2000), Pianta's Teacher-Child Interaction Questionnaire (1992), and the Autism Scale Questionnaire in the Social Interactions Subscale (1993) were used, and Martin's art therapy educational package (2009) was used for therapeutic intervention. became Collected data was analyzed using SPSS-27 software and analysis of variance test. The findings showed that art therapy based on painting has a significant effect on the teacher-child relationship, aggression and social interactions of children with autism spectrum disorder (p&lt;0.5). The child-teacher has reduced children's aggression.

Comparison of the Effectiveness of Schema-Based Parenting and Mindful Parenting on Sleep Problems, Aggression, and Improvement of Social Interactions in Children with Mild Autism Spectrum Disorder

Objective: The aim of the present study is to compare the effectiveness of schema-based parenting and mindful parenting on sleep problems, aggression, and improvement of social interactions in children with mild autism spectrum disorder. Methods and Materials: The present study is applied in terms of its aim and quasi-experimental in terms of method, using a pretest-posttest design with a control group and a one-month follow-up period. The statistical population includes all children aged 7-12 years with mild autism spectrum disorder who were studying and receiving education in one autism center under the supervision of the Ministry of Education (Tabassum) and five autism centers under the supervision of the Welfare Organization (Ava, Armaghan Noor, Kavosh, Navid-e-Zendegi, and Takapo) in Mashhad. The groupings were conducted through random assignment. Out of these, 40 children (20 boys and 20 girls) and 40 mothers were selected as the research sample using purposive sampling. They were then randomly assigned to three groups: two experimental groups (each with 13 members) and one control group (with 14 members). Data collection was conducted using the Autism Social Skills Profile by Belini and Hopf (2007), the CARS questionnaire by Schopler (1988), the Aggression Questionnaire, and the Children's Sleep Habits Questionnaire by Owens, Spirito, and colleagues (2000). After collecting the questionnaires, the data were analyzed using SPSS-20 software. Findings: The results indicated differences in the effectiveness of schema-based parenting and mindful parenting on aggression in children with mild autism spectrum disorder. Additionally, there were differences in the effectiveness of schema-based parenting and mindful parenting on the improvement of social interactions in children with mild autism spectrum disorder. Furthermore, differences were observed in the effectiveness of schema-based parenting and mindful parenting on sleep problems in children with mild autism spectrum disorder. Conclusion: The study demonstrated that both schema-based and mindful parenting interventions significantly reduce aggression and sleep problems while enhancing social interactions in children with mild autism spectrum disorder. These findings suggest the effectiveness of incorporating these approaches in parenting programs to improve behavioral and emotional outcomes in children.

Divergent electroencephalogram resting-state functional network alterations in subgroups of autism spectrum disorder: a symptom-based clustering analysis.

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

The role of adverse childhood experiences in obesity among adolescents with autism spectrum disorder: National survey of Children’s health 2018-2019

BackgroundAdolescents with autism spectrum disorder (ASD) are at an increased risk of overweight/obesity and adverse childhood experiences (ACEs). ObjectiveThis study examined whether ACEs increased the odds of overweight/obesity in adolescents with ASD. MethodsThis cross-sectional study used National Survey of Children's Health (NSCH) 2018-2019 data (N = 31,533 children ages 10–17 years, including n = 480 children with mild ASD and n = 423 children with moderate/severe ASD with normal or overweight/obese BMI). Parent-reported body mass index (BMI) was coded as overweight/obesity vs. normal weight. The independent variable was the count of nine ACEs. Binary logistic regression was conducted, controlling for social ecological factors. ResultsThe odds of overweight/obesity in adolescents with ASD with 1–2 ACEs (OR 1.3, CI 1.1-1.4) and 3+ ACEs (OR 1.6, CI 1.3-2.0) were higher than those with 0 ACEs; odds increased with higher counts of ACEs. Household income level was the most significant sociodemographic influence on odds of obesity in adolescents with ASD (0–99 % Federal Poverty Level: OR 1.9, CI 1.6-2.3). Adolescents with moderate/severe ASD (OR 1.7, CI 1.2-2.5) and mild ASD (OR 1.6, CI 1.0-2.4) had higher odds of overweight/obesity after accounting for ACEs, race/ethnicity, sex, household income, and physical activity. ConclusionFindings indicated ACEs are associated with ASD, which calls for integration of ACEs information within trauma-informed care practices for obesity prevention and intervention for adolescents with ASD. Persistent disparities of overweight/obesity exist by race/ethnicity, sex, and household income within this population, which indicates the need for tailoring trauma-informed approaches to the unique needs of this population.

A personalized classification of behavioral severity of autism spectrum disorder using a comprehensive machine learning framework

Autism Spectrum Disorder (ASD) is characterized as a neurodevelopmental disorder with a heterogeneous nature, influenced by genetics and exhibiting diverse clinical presentations. In this study, we dissect Autism Spectrum Disorder (ASD) into its behavioral components, mirroring the diagnostic process used in clinical settings. Morphological features are extracted from magnetic resonance imaging (MRI) scans, found in the publicly available dataset ABIDE II, identifying the most discriminative features that differentiate ASD within various behavioral domains. Then, each subject is categorized as having severe, moderate, or mild ASD, or typical neurodevelopment (TD), based on the behavioral domains of the Social Responsiveness Scale (SRS). Through this study, multiple artificial intelligence (AI) models are utilized for feature selection and classifying each ASD severity and behavioural group. A multivariate feature selection algorithm, investigating four different classifiers with linear and non-linear hypotheses, is applied iteratively while shuffling the training-validation subjects to find the set of cortical regions with statistically significant association with ASD. A set of six classifiers are optimized and trained on the selected set of features using 5-fold cross-validation for the purpose of severity classification for each behavioural group. Our AI-based model achieved an average accuracy of 96%, computed as the mean accuracy across the top-performing AI models for feature selection and severity classification across the different behavioral groups. The proposed AI model has the ability to accurately differentiate between the functionalities of specific brain regions, such as the left and right caudal middle frontal regions. We propose an AI-based model that dissects ASD into behavioral components. For each behavioral component, the AI-based model is capable of identifying the brain regions which are associated with ASD as well as utilizing those regions for diagnosis. The proposed system can increase the speed and accuracy of the diagnostic process and result in improved outcomes for individuals with ASD, highlighting the potential of AI in this area.

FRI479 Resistance To Thyroid Hormone Due To Thyroid Hormone Receptor Alpha (THRA) Gene Mutation

Abstract Disclosure: J.O. Abdelkarim: None. S. Parveen: None. M.G. Jakoby: None. J. Fleischer: None. Introduction: Resistance to thyroid hormone (RTH) is a heritable disorder characterized by diminished response to triiodothyronine (T3). Most cases of RTH are due to mutations in the thyroid hormone receptor beta (THRB) gene (“RTH-beta”). Mutations in thyroid hormone receptor alpha (THRA) gene appear to be a rare cause of RTH (“RTH-alpha”), with the first case reported in 2012. We present a case of RTH-alpha in a patient confirmed to have a pathogenic THRA mutation. Clinical Case: A 38-year-old Caucasian male was referred to genetic clinic due to mild developmental delay, dyscalculia and mild autism spectrum disorder. He was born at term by uncomplicated spontaneous vaginal delivery. Parents first noticed developmental delays at age 5 y, though no evaluation occurred during childhood. As an adult, the patient completed seminary studies and was employed as a Catholic priest. An intellectual disability gene panel revealed a pathogenic variant of the THRA gene (c.1151G&amp;gt;A p.R384H). Both parents tested negative for the mutation. Examination was notable for obesity (183 cm, 186 kg, BMI 55.5), macrocephaly, hypertelorism, pectus excavatum and small hands with short digits. No thyroid anatomic thyroid abnormalities were appreciated on neck examination or ultrasonography. TSH was 1.860 mIU/L (0.358-3.740), free T4 0.71 ng/dL (0.76-1.46), and free T3 3.2 pg/mL (2.2-4.0). The patient had no symptoms of hypothyroidism, and supplemental thyroid hormone was deferred. Discussion: There are 29 reported THRA gene mutations and 32 cases of RTH-alpha reported in the peer reviewed literature. Common clinical features include mild-to-moderate intellectual impairment, low basal metabolic rate (BMR), mild skeletal dysplasia, normocytic anemia, bradycardia, consistent with high expression of THRA in brain, heart, gastrointestinal tract, skeletal muscle, and bone. TSH is normal to slightly increased, free T4 is low to low normal, and free T3 is normal to modestly elevated. This is the third reported case of the c.1151G&amp;gt;A missense mutation resulting in an arginine to histidine substitution at codon 384. Thyroid function tests conform to the pattern described for other cases of RTH-alpha. Like the other two patients with the R384H mutation, developmental delays occurred, though intellectual manifestations mitigated with time and the patient completed seminary studies without difficulty. Mitigation of phenotype with age has been reported in RTH-alpha mice with the R384C missense mutation. Short stature did not occur in this patient or the other R384H cases. Unlike other patients, this patient did not experience anemia or constipation. Macrocephaly is a common feature of the three R384H cases, but the patient’s other skeletal manifestations (e.g. pectus excavatum) were not reported. This case demonstrates the difficulty of recognizing THR-alpha and extends our understanding of the R384H phenotype. Presentation: Friday, June 16, 2023

Effect of Kinesthetic-based Perceptual Integrative Games on Visual Perception and Academic Performance in Children with Autism Spectrum Disorder: A Quasi-Experimental Study

Abstract Background: Children learn everything through play and games. Visual perceptual skills are prerequisites for other areas of functioning, such as academic skills, activities of daily living, play, and leisure activities. Hence, visual perception can be improved using kinesthetic movement-based perceptual integrative games, as the children will be more interested in games rather than doing activities. Objective: The study aimed to identify the effect of kinesthetic-based perceptual integrative games on visual perception and academic performance in children with autism spectrum disorder (ASD). Study Design: Quasi-experimental study design was used. Methods: Fifty children diagnosed with mild and moderate ASD were selected based on convenient sampling. The experimental group (n = 25) received the kinesthetic-based perceptual integrative games for 36 sessions, 45 min per session, while the control group (n = 25) received conventional occupational therapy for the same period. Beery–Buktenica Developmental Test of Visual-Motor Integration (Berry VMI) scale and Academic Performance Rating Scale (APRS) were used. Results: The result revealed that the kinesthetic-based perceptual integrative games significantly improved visual perception (P = 0.042, 95% confidence level (CL) range 13.326–0.846) and academic performance (P = 0.001, 95% CL range of − 8.3718–−2.1882) compared to conventional occupational therapy but there was no correlation between the APRS and Berry VMI (P = 0.114). Conclusion: The kinesthetic-based perceptual integrative games intervention improved the visual perceptual skills and academic performance of children with ASD in this study. Hence, it can be used as a new therapeutic modality in treating children with ASD and other forms of disorders who have deficits in visual perception and academic skills.

Penerapan Prompts dan Reinforcement untuk Meningkatkan Frekuensi Kontak Mata pada Anak dengan Autisme

Children with autism spectrum disorder (ASD) have deficits in the ability to interact and communicate socially. The deficit in communication skills is also seen in the lack of eye contact displayed by ASD children. Eye contact plays a vital role in child development, such as responding to interactions, following instructions, and acquiring vocabulary and educational understanding. This intervention aims to increase the frequency of eye contact in a 4-year-old boy (N = 1) with mild ASD and language impairment. Researchers used prompts and reinforcement techniques, considered adequate for improving social skills in children with neurodevelopmental disorders. Researchers use designs A (Baseline) and B (Intervention). The results showed an increase in the frequency of eye contact with the subject from 0-2 times to 10 times in one session consisting of 10 times calling the child's name. Furthermore, this intervention also found an increase in children's eye contact when carried out by parents at home.

Leukocyte cytokine expression is associated with severity of autism in children

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with unknown etiology, high clinical heterogeneity and marked aberrations of the immune system. Evidence for an association between immune dysfunction and behavioral traits highlights the need for a study of the immune cell functional activity in order to search for pathogenesis mechanisms and potential targets for therapy at ASD. The purpose: to determine the expression levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, IFNγ and TNFα in peripheral blood leukocytes of children with mild and severe ASD. The study included 81 children with ASD (77.8% boys) and 45 children with typical neurodevelopment (TDC, 71.1% boys). According to the Childhood Autism Rating Scale, 51 children (63.0%) had mild autistic symptoms (CARS score 32.0±1,5) and 30 children had severe ASD symptoms (CARS score 39.0±3,4). Cytokines expression in leukocytes was determined by quantitative PCR with SYBRGreen. The data were transformed using Box–Cox transformation. The differences between groups were assessed by one-way ANOVA and Dunn’s test for multiple comparisons. In leukocytes of children with ASD, regardless of the severity, the expression of IL-1β, IL-18 and IL-2, was significantly reduced compared to TDC. Moreover, in children with mild ASD, low expression of TNFα, compared with TDC was found. In children with severe ASD, the expression of the main cytokine of Th1 – IFNγ, was significantly increased, without an increased expression of an important cytokine of Treg – IL-10. Activation of the Th1 adaptive immune response without compensation by cytokines of Treg, the number of which is reduced in ASD, can lead to increased inflammation, even in the central nervous system, and correlates with the severity of ASD clinical symptoms. Despite extensive immunological evidence suggesting immune system dysregulation, further research is required to clarify the relationship between immune system cell function and ASD pathology.

Signes cliniques précoces chez les enfants porteurs d’un TSA léger : description et effet de genre

BackgroundIn our Autism Spectrum Disorders Reference Center, we meet young people with mild autism spectrum disorder (ASD) with normal intellectual and language skills. The objective of this article was to characterize this population by analyzing the specific profile of these young people: first signs of concern, age of diagnosis in relation to more severe disorders, previous diagnoses, and reason for the assessment. In addition, we wanted to pay particular attention to the profiles of girls with mild ASD. MethodWe carried out a retrospective study based on the analysis of the clinical records of patients with a diagnosis of autism spectrum disorder of mild intensity according to the DSM-5, having benefited from a diagnostic assessment in our service. From the patient clinical files, we compared several elements: reason for the request, requesting persons, possible previous diagnoses, common early clinical signs. We have for each element distinguished girls and boys. ResultsWe studied a population of 33 young people with mild ASD. The assessment is most often requested by parents in the context of social interaction disorders. The average age of diagnosis is higher than in children with moderate or severe ASD, and young people have sometimes received other past diagnoses. We were able to highlight certain early signs in terms of language, sleep, food, sensory sensitivities, emotional regulation and socialization, signs that are, however, not very specific. No significant difference but rather tendencies were highlighted between girls and boys, probably related to the small size of the sample. DiscussionThe retrospective nature of this study, the sample size and the absence of a control group are limitations. However, a certain camouflage, early non-specific signs as well as sometimes less suitable diagnostic tools can explain a later diagnosis in young carriers of mild ASD, some of whom have also received another diagnosis in the past. An attitude of denial of the difficulties on the part of the parents is sometimes also mentioned. As far as girls are concerned, we found them in a higher proportion than expected, given the literature which describes a sex ratio quite different from ours. ConclusionIf the early and late clinical signs concerning mild ASD are better and better known from a theoretical point of view, the diagnosis does not seem to be facilitated for all that. Also, raising the awareness of parents and first-line caregivers is required to detect children with mild ASD early in order to refer them to specialists in this disorder. Given the number of girls in our sample, it seems that they likely benefited from effective screening. A future study could relate to a comparison of our population with a control group, in order to refine the specificity of any early symptoms.