Autism Spectrum Disorder Symptom Severity Research Articles

Younger age is associated with better outcomes in autism severity, language, and adaptive skills after one school year in autism special education classes

A well-accepted hypothesis in the field of autism spectrum disorder (ASD) is that early intervention is crucial for better outcomes. However, research has noted significant variability in early intervention outcomes. This study examined the role of age in relation to outcomes in comprehensive developmental domains following one year of school in community special education classes for ASD. We compared two groups: a younger group (n = 35) aged 34–59 months and an older group (n = 38) aged 60–91 months. The groups did not differ in cognitive ability, autism severity or adaptive behavioral skills at the start of the school year. After one year, the entire study population showed significant progress in all developmental domains. However, changes in effect size were much more robust in the younger ASD group. Only younger children showed a significant decrease in the severity of communication, awareness and restricted interests and repetitive behavior subdomains and a significant increase in motor adaptive skills. Younger children also showed more remarkable improvement in the naming and expressive subdomains. Respectively, older age predicted more severe ASD symptoms at the end of the educational year.Corresponding to brain plasticity theories, our findings point to an association between age and outcomes. The findings should serve as a benchmark for policymakers regarding early intervention in young children with autism.

Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits

BackgroundDietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children with ASD are poorly understood. This study firstly compared the dietary intake and GI symptoms between children with ASD and typically developing children (TDC), and then quantified the relative contributions of autism-linked traits to dietary intake, and relative contributions of autism-linked traits and dietary intake to GI symptoms within the ASD group.MethodsA sample of 121 children with ASD and 121 age-matched TDC were eligible for this study. The dietary intake indicators included food groups intakes, food variety, and diet quality. The autism-linked traits included ASD symptom severity, restricted repetitive behaviors (RRBs), sensory profiles, mealtime behaviors, and their subtypes. Linear mixed-effects models and mixed-effects logistic regression models were used to estimate the relative contributions.ResultsChildren with ASD had poorer diets with fewer vegetables/fruits, less variety of food, a higher degree of inadequate/unbalanced dietary intake, and more severe constipation/total GI symptoms than age-matched TDC. Within the ASD group, compulsive behavior (a subtype of RRBs) and taste/smell sensitivity were the only traits associated with lower vegetables and fruit consumption, respectively. Self-injurious behavior (a subtype of RRBs) was the only contributing trait to less variety of food. Limited variety (a subtype of mealtime behavior problems) and ASD symptom severity were the primary and secondary contributors to inadequate dietary intake, respectively. ASD symptom severity and limited variety were the primary and secondary contributors to unbalanced dietary intake, respectively. Notably, unbalanced dietary intake was a significant independent factor associated with constipation/total GI symptoms, and autism-linked traits manifested no contributions.ConclusionsASD symptom severity and unbalanced diets were the most important contributors to unbalanced dietary intake and GI symptoms, respectively. Our findings highlight that ASD symptom severity and unbalanced diets could provide the largest benefits for the dietary and GI problems of ASD if they were targeted for early detection and optimal treatment.

Changes in Behaviours Following an Integrative Exercise Intervention in Children with Autism Spectrum Disorder: The Influence of Symptom Severity

ABSTRACT The current study investigated the effects of an integrative exercise intervention on the behaviours in children with autism spectrum disorder (ASD), and if they were influenced by ASD symptom severity. Sixty-six children (7.56 ± 2.03 yrs.) with ASD were enrolled and categorised as having mild (n = 22), moderate (n = 18) or severe (n = 26) symptoms of ASD by teachers using the Gilliam Autism Rating Scale 2nd edition. Participants completed a school-based, eight-week, integrative exercise intervention, consisting of three, one-hour sessions per week. Teachers rated the symptoms of ASD in each participant pre- and post-intervention using the Aberrant Behaviour Checklist. There were significant improvements in behaviours post-intervention for all children (p < 0.05; r = 0.20–0.33); however, sub-group analysis indicated that participants with severe ASD experienced greater improvements in irritability, social withdrawal, stereotypic behaviour, and inappropriate speech (p < 0.05). The findings highlight the benefits of school-based integrative exercise interventions for improving behaviours in children with ASD.

Affiliate Stigma Among Caregivers of Children with Autism Spectrum Disorder: The Role of Coping Strategies and Perceived Social Support

Caregivers of children with autism spectrum disorder (ASD) may experience stigma due to ASD-related symptoms. However, factors such as coping strategies and perceived social support might impact the affiliate stigma they experience. To date, no research has explored the association between ASD symptom severity and affiliate stigma, considering the role of coping strategies and perceived social support in different cultural contexts. This study aimed to test a hypothesized model in which coping strategies and perceived social support mediate the association between children’s ASD symptom severity and caregivers’ affiliate stigma. A cross-sectional study was conducted among 392 caregivers of children with ASD in Saudi Arabia. Data were collected using structured interviews with eligible caregivers at a developmental and behavioral disorder clinic, five daycare centers, and three schools. The hypothesized model was tested using structural equation modeling. The study found that caregivers of children with ASD reported experiencing affiliate stigma. Additionally, as the severity of children’s ASD symptoms increased, caregivers’ perceptions of affiliate stigma also increased. However, both maladaptive coping strategies and perceived social support mediated this relationship. The findings emphasize the importance of addressing the psychosocial needs of caregivers of children with ASD, particularly by decreasing the use of maladaptive coping strategies and providing social support to minimize their experience of affiliate stigma.

Using visual attention estimation on videos for automated prediction of autism spectrum disorder and symptom severity in preschool children.

Atypical visual attention in individuals with autism spectrum disorders (ASD) has been utilised as a unique diagnosis criterion in previous research. This paper presents a novel approach to the automatic and quantitative screening of ASD as well as symptom severity prediction in preschool children. We develop a novel computational pipeline that extracts learned features from a dynamic visual stimulus to classify ASD children and predict the level of ASD-related symptoms. Experimental results demonstrate promising performance that is superior to using handcrafted features and machine learning algorithms, in terms of evaluation metrics used in diagnostic tests. Using a leave-one-out cross-validation approach, we obtained an accuracy of 94.59%, a sensitivity of 100%, a specificity of 76.47% and an area under the receiver operating characteristic curve (AUC) of 96% for ASD classification. In addition, we obtained an accuracy of 94.74%, a sensitivity of 87.50%, a specificity of 100% and an AUC of 99% for ASD symptom severity prediction.

The utilization of psychopharmacological treatments for individuals with autism spectrum disorder (ASD) in a middle-income European country

BackgroundStudies examining the utilization of psychopharmacological treatments (psychotropic medications) for autism spectrum disorder (ASD) have primarily been carried out in affluent nations. Nonetheless, there is an evident dearth of data originating from low- and middle-income countries. Our study sought to comprehensively evaluate the usage of psychopharmacological treatments and the effectiveness of those treatments as perceived by the parents of individuals with autism spectrum disorder (ASD) in Macedonia, a middle-income country in South-Eastern Europe. MethodsWe conducted a survey involving 103 parents of individuals with ASD and analyzed the questionnaire responses using descriptive statistics and non-parametric tests. ResultsOur research uncovered that 62% of individuals diagnosed with ASD were prescribed psychopharmacological treatments, yet only 48% actually utilized them. Among the medications prescribed, antipsychotics (55%) and antiepileptics (44%) were the most common, with risperidone and valproate being the preferred options. Psychopharmacological treatments were found to be more commonly used among individuals aged 15 years and above, with children under 8 years closely following suit at a rate of 56%. Furthermore, we discovered a noteworthy association between the severity of ASD symptoms and the utilization of these interventions. Intriguingly, the majority of parents (73%) regarded the effectiveness of psychopharmacological treatments as only partially effective. ConclusionOur study emphasizes the prevalent utilization of psychotropic medication, especially among young individuals, and underscores the necessity for enhanced dissemination of information to parents regarding prescribed medications. By integrating our research findings, medical professionals and policymakers can enhance the strategies and initiatives used to improve the quality of care and support for individuals on the autism spectrum.

Utility of the Language Use Inventory in Young Children at Elevated Likelihood of Autism.

The aims of this study were (a) to evaluate the convergent validity of the Language Use Inventory (LUI) with measures of autism spectrum disorder (ASD) symptoms, language, and social skills and (b) to assess discriminant validity of the LUI with measures of nonlanguage skills, including daily living skills and motor development. This study sample included participants from a longitudinal study (n = 239) of infant siblings with elevated familial likelihood of ASD and lower familial likelihood. Assessment measures completed at 36 months included the LUI, the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), the Mullen Scales of Early Learning, and the Vineland Adaptive Behavior Scales-Second Edition. Bivariate Pearson correlations were estimated between ADOS-2 comparison scores and four language and social skills measures. Additional correlations were estimated between LUI total scores and standard scores from nonlanguage measures. A series of Fisher's Z transformations were applied to evaluate whether bivariate correlations were significantly different. All four language and social skill measures were moderately to strongly associated with each other and ASD symptom severity scores. The correlation between ADOS-2 comparison scores and LUI total scores was significantly stronger than ADOS-2 correlations with all other measures. Our findings provide support for the LUI as a feasible, pragmatic language-targeted instrument for inclusion in early developmental evaluations prompted by language concerns. Administration of the LUI may accelerate earlier referral for a comprehensive assessment of ASD symptoms. Given the high correlation with ADOS-2 scores, an LUI total score in a clinical range of concern may encourage a clinician to refer families for a full diagnostic evaluation of ASD.

Decreased wrist rotation imitation abilities in children with autism spectrum disorder.

While meaningless gross motor imitation (GMI) is a common challenge for children diagnosed with autism spectrum disorder (ASD), this topic has not attracted much attention and few appropriate test paradigms have been developed. The current study proposed a wrist rotation imitation (WRI) task (a meaningless GMI assignment), and established a WRI ability evaluation system using low-cost wearable inertial sensors, which acquired the simultaneous data of acceleration and angular acceleration during the WRI task. Three metrics (i.e., total rotation time, rotation amplitude, and symmetry) were extracted from those data of acceleration and angular acceleration, and then were adopted to construct classifiers based on five machine learning (ML) algorithms, including k-nearest neighbors, linear discriminant analysis, naive Bayes, support vector machines, and random forests. To illustrate our technique, this study recruited 49 ASD children (aged 3.5-6.5 years) and 59 age-matched typically developing (TD) children. Findings showed that compared with TD children, those with ASD may exhibit shorter total rotation time, lower rotation amplitude, and weaker symmetry. This implies that children with ASD might exhibit decreased WRI abilities. The classifier with the naive Bayes algorithm outperformed than other four algorithms, and achieved a maximal classification accuracy of 88% and a maximal AUC value of 0.91. Two metrics (i.e., rotation amplitude and symmetry) had high correlations with the gross and fine motor skills [evaluated by Gesell Developmental Schedules-Third Edition and Psychoeducational Profile-3 (PEP-3)]. While, the three metrics had no significant correlation with the visual-motor imitation abilities (evaluated by the subdomain of PEP-3) and the ASD symptom severity [evaluated by the Childhood Autism Rating Scale (CARS)] . The strengths of this study are associated with the low-cost measurement system, correlation between the WRI metrics and clinical measures, decreased WRI abilities in ASD, and high classification accuracy.

Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) affects up to 1 in 36 children in the United States. It is a heterogeneous neurodevelopmental disorder with life-long consequences. Patients with ASD and folate pathway abnormalities have demonstrated improved symptoms after treatment with leucovorin (folinic acid), a reduced form of folate. However, biomarkers for treatment response have not been well investigated and clinical trials are lacking. In this retrospective analysis, a cohort of prospectively collected data from 110 consecutive ASD clinic patients [mean (SD) age: 10.5 (6.2) years; 74% male] was examined. These patients all underwent testing for folate receptor alpha autoantibodies (FRAAs) and soluble folate binding proteins (sFBPs) biomarkers and were treated with leucovorin, if appropriate. Analyses examined whether these biomarkers could predict response to leucovorin treatment as well as the severity of ASD characteristics at baseline. The social responsiveness scale (SRS), a measure of core ASD symptoms, and the aberrant behavior checklist (ABC), a measure of disruptive behavior, were collected at each clinic visit. Those positive for sFBPs had more severe ASD symptoms, and higher binding FRAA titers were associated with greater ABC irritability. Treatment with leucovorin improved most SRS subscales with higher binding FRAA titers associated with greater response. Leucovorin treatment also improved ABC irritability. These results confirm and expand on previous studies, underscore the need for biomarkers to guide treatment of folate pathways in ASD, and suggest that leucovorin may be effective for children with ASD.

Serum Zonulin, Claudin-5, junction Adhesion Molecule-A, Occludin and Tricellulin levels in children with autism spectrum disorder

Introduction The aim of this study is to determine whether there is a difference in serum Zonulin, Occludin, Claudin-5, Junctional Adhesion Molecule-A (JAM-A), Tricellulin levels between individuals diagnosed with Autism Spectrum Disorder (ASD) and healthy controls. Method A total of 40 children with ASD and 40 controls aged 2-12 years were enrolled in this study. Serum levels of biochemical variables were determined using commercial enzyme-linked immunosorbent assay kits. Childhood Autism Rating Scale, Autism Behavior Checklist and Aberrant Behavior Checklist were applied to determine the severity of autistic symptoms. Results Serum Zonulin, Occludin, Claudin-5, Tricellulin and JAM-A levels did not differ between the study and control groups. There was no relationship between the severity of ASD symptoms and biochemical parameters. Discussion Although the findings of the study suggest that the permeability of the Blood Brain Barrier (BBB) is not effective in the etiology of ASD, there is a need for new studies addressing the limitations of our study in a larger and heterogeneous sample in order to generalize the findings.

Once upon a Time Oral Microbiota: A Cinderella or a Protagonist in Autism Spectrum Disorder?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder evolving over the lifetime of individuals. The oral and gut microbial ecosystems are closely connected to each other and the brain and are potentially involved in neurodevelopmental diseases. This narrative review aims to identify all the available evidence emerging from observational studies focused on the role of the oral microbiome in ASD. A literature search was conducted using PubMed and the Cochrane Library for relevant studies published over the last ten years. Overall, in autistic children, the oral microbiota is marked by the abundance of several microbial species belonging to the Proteobacteria phylum and by the depletion of species belonging to the Bacteroidetes phylum. In mouse models, the oral microbiota is marked by the abundance of the Bacteroidetes phylum. Oral dysbiosis in ASD induces changes in the human metabolome, with the overexpression of metabolites closely related to the pathogenesis of ASD, such as acetate, propionate, and indoles, together with the underexpression of butyrate, confirming the central role of tryptophan metabolism. The analysis of the literature evidences the close relationship between oral dysbiosis and autistic core symptoms; the rebuilding of the oral and gut ecosystems by probiotics may significantly contribute to mitigating the severity of ASD symptoms.

Family Functioning and Strengths in Families of Children With Autism Spectrum Disorder in Saudi Arabia

The purpose of this study was to investigate the relationship between family functioning and strengths in the context of parents of children with autism spectrum disorder (ASD) in Saudi Arabia. A total of 300 parents of a child with ASD completed a self-report questionnaire, the Family Adaptability and Cohesion Evaluation Scales (FACES IV), Family Communication Scale (FCS), Family Satisfaction Scale (FSS), and Family Strengths Scale, to measure different balanced and unbalanced aspects of family cohesion and flexibility, family communication skills, extent of satisfaction with family functioning, and the accord and pride facets of family strength. The data were analyzed using independent sample t-test, F-test, and ANOVA. The severity of child's ASD symptoms and age of the child when diagnosed with ASD had a significant effect on a family's cohesion and flexibility, communication, and accord. The parents’ years of marriage and annual income also had a significant effect on cohesion, flexibility, communication, and family strengths. Contributions of the study, limitations, and implications for future research and practice are provided.

Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder

Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography–mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

The Effects of Prebiotics and Probiotics Following Antibiotic Exposure in a Mouse Model of Autism Spectrum Disorder: A Research Protocol

The human microbiota consists of 10-100 trillion symbiotic microbial cells critical for one’s digestive system, immune system and for managing neurological symptoms experienced in neurodevelopmental conditions. With early exposure to antibiotics, an individual’s microbiome composition is negatively affected by reducing the diversity of microbial species found in the microbiome and can lead to an imbalance in the Gut-Brain-Axis (GBA). While the direct relationship between the GBA and neurodevelopmental functioning is still unclear, evidence suggests that individuals with a disruptive microbiome and an imbalanced GBA have an increased risk of developing neurodevelopmental disorders, specifically autism spectrum disorder (ASD). To improve microbiome diversity, exposure to a high prebiotic and probiotic diet in the early stages of life can reintroduce beneficial bacteria back into the microbiome and improve microbial diversity. Pre- and pro-biotics can improve microbiome diversity and restore balance to the GBA. With the introduction of a prebiotic and probiotic diet and a balanced GBA, there is a possibility to reduce the severity of ASD symptoms. By reducing the severity of ASD symptoms, the quality of life of those with severe ASD can potentially be improved allowing them to maintain functional independence. This research protocol intends to utilize an automated video tracking system and three-chambered social approach to evaluate the behavioural symptoms in BTBR strain mice which exhibit symptoms before and after administration of pre- and probiotics following antibiotic exposure.

The Zinc-Copper Connection In Autism Spectrum Disorder: Pioneering Work Of Dr. Geir Bjørklund

Abstract This interview delves into the relationship between zinc (Zn) and copper (Cu) in autism spectrum disorder (ASD), featuring insights from Dr. Geir Bjørklund, MD, a Norwegian researcher. Collaborative studies conducted across diverse countries, including China, Slovenia, Romania, Russia, Brazil, and Egypt, consistently reveal altered Zn and Cu levels in individuals with ASD. These findings suggest a potential correlation between elevated Cu levels and increased severity of ASD symptoms. Dr. Bjørklund emphasizes the multifaceted dynamics of metallothioneins (MTs), essential proteins for metal binding and detoxification, and their potential association with Zn deficiency in ASD individuals. The interview illuminates the balance between Zn and Cu within the GABAergic system, implicating these trace elements in synaptic modulation and broader neurobiological functions. Future research directions proposed by Dr. Bjørklund encompass exploring multiple biological mediums for accurate trace element assessment, investigating interactions between different trace elements, and exploring factors influencing trace element levels in various tissues. The significance of Zn supplementation in treating ASD, the implications of MT dysfunction, and the importance of dual monitoring of Cu and Zn during therapy are thoroughly discussed. The conclusion expresses gratitude for Dr. Bjørklund’s invaluable contributions to comprehending the role of Zn and Cu in ASD, highlighting the global relevance of his research and the need for a comprehensive approach to understanding trace element dynamics in this complex neurodevelopmental disorder.

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.

Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity.

This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6-40 years, (2) full-scale IQ < 84, and (3) language ≥3-word phrases. ASD symptom severity was determined by Autism Diagnostic Observation Schedule-2 (ADOS-2). Other measures identified non-verbal IQ, adaptive skills, and aberrant behaviors. Molecular measures included blood FMR1 and CYFIP1 mRNA levels, FMRP and MMP9 levels. Analysis of variance (ANOVA) and Spearman's correlations were used to compare ASD severity groups. Data from 54 individuals was included with no/mild (N= 7), moderate (N= 18), and severe (N= 29) ASD. Individuals with high ASD severity had lower adaptive behavior scores (47.48 ± 17.49) than the no/mild group (69.00 ± 20.45, p= 0.0366); they also had more challenging behaviors, lethargy, and stereotypic behaviors. CYFIP1 mRNA expression levels positively correlated with the ADOS-2 comparison score(r2 =0.33, p= 0.0349), with no significant correlations with other molecular markers. In conclusion, autism symptom severity is associated with more adverse cognitive and adaptive skills and specific behaviors in FXS, whereas CYFIP1 mRNA expression levels may be a potential biomarker for severity of ASD in FXS.

Nonlinear features of gaze behavior during joint attention in children with autism spectrum disorder.

Since children with autism spectrum disorder (ASD) might exhibit a variety of aberrant response to joint attention (RJA) behaviors, there is growing interest in identifying robust, reliable and valid eye-tracking metrics for determining differences in RJA behaviors between typically developing (TD) children and those with ASD. Previous eye-tracking studies have not been deeply investigated nonlinear features of gaze time-series during RJA. As a main motivation, this study aimed to extract three nonlinear features (i.e., complexity, long-range correlation, and local instability) of gaze time-series during RJA in children with ASD, which can be measured by fractal dimension (FD), Hurst exponent (H), and largest Lyapunov exponent (LLE), respectively. To illustrate our idea, this study adopted a publicly accessible database, including eye-tracking data collected during RJA from 19 children with ASD (7.74 ± 2.73) and 30 TD children (8.02 ± 2.89), and conducted a battery of nonparametric analysis of covariance (ANCOVA), where gender was used as covariable. Findings showed that gaze time-series during RJA in autistic children may generally have greater FD but lower H than that in TD controls. This implies that children with ASD possess more complex and unpredictable gaze behaviors during RJA than TD children. Furthermore, nonlinear metrics outperformed traditional eye-tracking metrics in obtaining higher identification performance with an accuracy of 82% and an AUC value of 0.81, distinguishing the differences between successful and failed RJA trails, and predicting the severity of ASD symptoms. Findings might bring some new insights into the understanding of the impairments in RJA behaviors for children with ASD.

Diagnostic Accuracy of Primary Care Clinicians Across a Statewide System of Autism Evaluation.

To evaluate the diagnostic accuracy of the Early Autism Evaluation (EAE) Hub system, a statewide network that provides specialized training and collaborative support to community primary care providers in the diagnosis of young children at risk for autism spectrum disorder (ASD). EAE Hub clinicians referred children, aged 14 to 48 months, to this prospective diagnostic study for blinded follow-up expert evaluation including assessment of developmental level, adaptive behavior, and ASD symptom severity. The primary outcome was agreement on categorical ASD diagnosis between EAE Hub clinician (index diagnosis) and ASD expert (reference standard). Among 126 children (mean age: 2.6 years; 77% male; 14% Latinx; 66% non-Latinx white), 82% (n = 103) had consistent ASD outcomes between the index and reference evaluation. Sensitivity was 81.5%, specificity was 82.4%, positive predictive value was 92.6%, and negative predictive value was 62.2%. There was no difference in accuracy by EAE Hub clinician or site. Across measures of development, there were significant differences between true positive and false negative (FN) cases (all Ps < .001; Cohen's d = 1.1-1.4), with true positive cases evidencing greater impairment. Community-based primary care clinicians who receive specialty training can make accurate ASD diagnoses in most cases. Diagnostic disagreements were predominately FN cases in which EAE Hub clinicians had difficulty differentiating ASD and global developmental delay. FN cases were associated with a differential diagnostic and phenotypic profile. This research has significant implications for the development of future population health solutions that address ASD diagnostic delays.

Goal-directed action anticipation and prediction error processing in children with autism spectrum disorders: An eye-movement study

BackgroundDifferences in predictive ability have been proposed as a possible explanation for the core symptoms of autism spectrum disorder (ASD). This study aimed to investigate potential differences in prior knowledge acquisition and application for goal-directed anticipation in children with ASD. MethodThe study included 22 children with ASD and 19 typically developing (TD) children between the ages of 5–10 years. Two eye-tracking phases were used to examine the formation of goal-directed action anticipations and the processing of action prediction errors. In the action anticipation formation phase, participants were asked to observe goal-directed actions repeatedly to examine prior knowledge acquisition about agent-goal association. In the action anticipation violation phase, the goals of actions were changed to examine the application of previously acquired knowledge. ResultsChildren with ASD required more trials to form goal-directed anticipations than TD children. Furthermore, prior knowledge acquisition was characterized by variability and instability in children with ASD. During the action anticipation violation phase, children with ASD exhibited lower preference for the action goal determined by prior knowledge in uncertain situations. This atypical processing of prior knowledge was significantly correlated with the severity of ASD symptoms. ConclusionsOur findings support the Bayesian perception theory and predictive coding theory, suggesting that children with ASD may experience difficulties in both the acquisition and application of prior knowledge in anticipation. These findings have implications for developing interventions to improve goal-directed anticipation and reduce social and communication difficulties in individuals with ASD.