Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Classifying autism in a clinical population based on motion synchrony: a proof-of-concept study using real-life diagnostic interviews.

Predictive modeling strategies are increasingly studied as a means to overcome clinical bottlenecks in the diagnostic classification of autism spectrum disorder. However, while some findings are promising in the light of diagnostic marker research, many of these approaches lack the scalability for adequate and effective translation to everyday clinical practice. In this study, our aim was to explore the use of objective computer vision video analysis of real-world autism diagnostic interviews in a clinical sample of children and young individuals in the transition to adulthood to predict diagnosis. Specifically, we trained a support vector machine learning model on interpersonal synchrony data recorded in Autism Diagnostic Observation Schedule (ADOS-2) interviews of patient-clinician dyads. Our model was able to classify dyads involving an autistic patient (n = 56) with a balanced accuracy of 63.4% against dyads including a patient with other psychiatric diagnoses (n = 38). Further analyses revealed no significant associations between our classification metrics with clinical ratings. We argue that, given the above-chance performance of our classifier in a highly heterogeneous sample both in age and diagnosis, with few adjustments this highly scalable approach presents a viable route for future diagnostic marker research in autism.

Descriptive Analysis of Social Interaction and Communication Skills of Autistic Children According to Sibling Status and Characteristics.

OBJECTIVE: Sibling relationships in early childhood can have a positive impact on children's social interaction and communication skills. Similarly, autistic children can benefit from interactions with their siblings, who can serve as readily available partners for social interaction. However, there is a lack of research on the effects of siblings based on specific characteristics of the sibling. Therefore, the aim of this study is to compare social interactions and communication skills of autistic children based on sibling status and characteristics. METHODS: We conducted a retrospective data review involving 895 autistic children and their siblings at Seoul National University Bundang Hospital. Variety of diagnostic assessments or questionnaires were administered. Based on the characteristics of the data, Quade's test for nonparametric analysis of covariance was used to compare autism-related symptoms and levels of functioning of the autistic child according to 1) sibling status, 2) birth order, 3) sex, and 4) diagnosis of the sibling. Pearson correlation was used to explore associations between the sibling age gap and different clinical scores. RESULTS: Having siblings was associated with fewer difficulties in restricted and repetitive behaviors. Based on the comparison of the Autism Diagnostic Interview-Revised scores, autistic children with multiple siblings demonstrated better nonverbal behaviors. Autistic children with autistic siblings experienced greater difficulties in social interactions and communications, such as peer relationships, sharing enjoyment, and engaging in social imitative play. CONCLUSION: The study revealed differences in social interactions and communication skills of autistic children based on sibling status, birth order, affected sibling, age gap, and sex.

Time to level up: A systematic review of interventions aiming to reduce stigma toward autistic people.

LAY ABSTRACT: How non-autistic people think about autistic people impacts autistic people negatively. Many studies developed trainings to reduce autism stigma. The existing trainings vary a lot in terms of study design, content, and reported effectiveness. This means that a review studying how the studies have been conducted is needed. We also looked at the quality of these studies. We collected and studied 26 studies that tried to reduce stigma toward autistic people. The studies often targeted White K-12 students and college students. Most trainings were implemented once. Trainings frequently used video or computer. Especially, recent studies tended to use online platforms. The study quality was poor for most studies. Some studies made inaccurate claims about the intervention effectiveness. Studies did not sufficiently address study limitations. Future trainings should aim to figure out why and how interventions work. How intervention changes people's behavior and thoughts should be studied. Researchers should study whether the training can change the societal stigma. Also, researchers should use a better study design.

Clinical characteristics of comorbid tic disorders in autism spectrum disorder: exploratory analysis.

BACKGROUND: The frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear. METHODS: We included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4-18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive-Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26. RESULTS: Tic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70). CONCLUSIONS: The IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD. Trial registration This study retrospectively registered participants.

Improving adaptive behaviors for autistic adults without intellectual disability through executive function training.

Executive functioning (EF) is a cognitive process used to perform various daily activities throughout one's lifespan. Autistic adults without intellectual disabilities (ID) also experience difficulties with EF, which is closely associated with adaptive behaviors. For this reason, it is important to improve adaptive behaviors through enhanced use of EF for autistic adults to transition into adulthood successfully. This study aims to conduct a randomized controlled trial to evaluate the effectiveness of a newly developed and modified intervention program. Thirty autistic adults without ID were randomly assigned to the treatment or waitlist group. The participants and caregivers completed various assessments and self-report questionnaires to measure everyday EF and adaptive behaviors. We performed linear mixed-effect modeling to compare the two groups. Data collected at pre-, middle, post-, and follow-up based on participants who completed the program were used to explore changes across time. While there were significant differences in the EF utility-scale (F=5.46, p = .027) between the treatment and waitlist groups, no group x time interactions were detected in other measures. Everyday EF and adaptive behaviors improved when comparing measurements at different time points (p < .001). Our program is Korea's first evidence-based intervention to improve everyday EF and adaptive behaviors for autistic adults without ID.

Loss of Acquired Skills: Regression in Young Children With Autism Spectrum Disorders.

Objectives: Regression, while not a core symptom of autism spectrum disorder (ASD), has been suggested to be a distinct subtype by previous studies. Therefore, this study aimed to explore the prevalence and clinical differences between those with and without regression in children with ASD. Methods: This study includes data from toddlers and young children aged 2-7 years acquired from other projects at Seoul National University Bundang Hospital. The presence and characteristics of regression were explored using question items #11-28 from the Autism Diagnostic Interview-Revised. Chi-square and independent t-tests were used to compare various clinical measurements such as autistic symptoms, adaptative behavior, intelligence, and perinatal factors. Results: Data from 1438 young children (1020 with ASD) were analyzed. The overall prevalence rate of regression, which was mainly related to language-related skills, was 10.2% in the ASD group, with an onset age of 24 months. Regarding clinical characteristics, patients with ASD and regression experienced ASD symptoms, especially restricted and repetitive interests and behaviors, with greater severity than those without regression. Furthermore, there were significant associations between regression and hypertension/placenta previa. Conclusion: In-depth surveillance and proactive interventions targeted at young children with ASD and regression should focus on autistic symptoms and other areas of functioning.

A systematic review and meta-analysis of associations between primarily non-autistic people's characteristics and attitudes toward autistic people.

This systematic review includes a narrative synthesis and meta-analysis of research on the associations between primarily non-autistic people's characteristics and their attitudes toward autistic people. Of 47 studies included in the narrative synthesis, White undergraduate students were surveyed most frequently. Demographic characteristics were the factors most frequently tested for associations with attitudes, followed by contact-related factors (i.e., quantity and quality), knowledge about autism, trait and personality factors, and other factors that did not fit into a single category. Internal consistency was not reported for some instruments assessing raters' characteristics; some instruments had alpha levels lower than 0.70, and many characteristics of raters were measured using one-item measures. Moreover, theoretical motivations for investigating the raters' characteristics were rarely provided. A total of 36 studies were included in the meta-analysis, which showed that attitudes toward autistic people were significantly associated with participants' gender, knowledge about autism, and quality and quantity of their previous contact with autistic people, but not with their age or autistic traits. These findings indicate a need for more studies that focus on context-related characteristics (e.g., institutional variables such as support/commitment to inclusion), use reliable instruments to measure non-autistic people's characteristics, and situate their investigation in a theoretical framework.

Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population.

BACKGROUND: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS-2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. METHOD: Data from 2,158 participants were included (mean age = 79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n = 289; Module 1, n = 642; Module 2 n = 574; Module 3 n = 411; Module 4, n = 242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's α values were also calculated. RESULTS: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4-100.0%; specificity, 80.4-96.8%; area under the ROC curve, .90-.97; PPV, 77.8-99.3%; NPV, 80.6-100.0%; and k values, .83-.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from .20 to .90. Cronbach's α values ranged from .82 to .91 across all developmental cells. LIMITATION: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. CONCLUSION: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed.

Patterns of Restricted and Repetitive Behaviors in Toddlers and Young Children with Autism Spectrum Disorder.

Objectives: Restricted and repetitive behaviors (RRBs) are a core symptom in the diagnosis of autism spectrum disorder (ASD). The complexity of behavioral patterns has called for the creation of phenotypically homogeneous subgroups among individuals with ASD. The purpose of this study was 1) to investigate the different types of RRBs and 2) to explore whether subgroups created by RRBs would show unique levels of functioning in toddlers and young children with ASD. Methods: A total of 313 children with ASD, aged 12-42 months were included in the analysis. The Autism Diagnostic Interview-Revised was used to obtain information on the different types of RRBs by grouping 15 items into six categories. The Vineland Adaptive Behaviors Scale, a parent-reported questionnaire, was used to measure adaptive functioning. A portion of the children were analyzed separately for verbal-related RRBs based on their expressive language level. Two-step cluster analysis using RRB groups as features was used to create subgroups. Analysis of covariance while covarying for age and language was performed to explore the clinical characteristics of each cluster group. Results: Sensory-related RRBs were the most prevalent, followed by circumscribed interests, interest in objects, resistance to change, and repetitive body movements. A subset of the children was analyzed separately to explore verbal-related RRBs. Four cluster groups were created based on reported RRBs, with multiple RRBs demonstrating significant delays in adaptive functioning. Conclusion: Heterogeneity of RRBs emerges at a young age. The different patterns of RRBs can be used as valuable information to determine developmental trajectories with better implications for treatment approaches.

Machine learning with neuroimaging data to identify autism spectrum disorder: a systematic review and meta-analysis.

PURPOSE: Autism Spectrum Disorder (ASD) is diagnosed through observation or interview assessments, which is time-consuming, subjective, and with questionable validity and reliability. Thus, we aimed to evaluate the role of machine learning (ML) with neuroimaging data to provide a reliable classification of ASD. METHODS: A systematic search of PubMed, Scopus, and Embase was conducted to identify relevant publications. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess the studies' quality. A bivariate random-effects model meta-analysis was employed to evaluate the pooled sensitivity, the pooled specificity, and the diagnostic performance through the hierarchical summary receiver operating characteristic (HSROC) curve of ML with neuroimaging data in classifying ASD. Meta-regression was also performed. RESULTS: Forty-four studies (5697 ASD and 6013 typically developing individuals [TD] in total) were included in the quantitative analysis. The pooled sensitivity for differentiating ASD from TD individuals was 86.25 95% confidence interval [CI] (81.24, 90.08), while the pooled specificity was 83.31 95% CI (78.12, 87.48) with a combined area under the HSROC (AUC) of 0.889. Higgins I2 (> 90%) and Cochran's Q (p < 0.0001) suggest a high degree of heterogeneity. In the bivariate model meta-regression, a higher pooled specificity was observed in studies not using a brain atlas (90.91 95% CI [80.67, 96.00], p = 0.032). In addition, a greater pooled sensitivity was seen in studies recruiting both males and females (89.04 95% CI [83.84, 92.72], p = 0.021), and combining imaging modalities (94.12 95% [85.43, 97.76], p = 0.036). CONCLUSION: ML with neuroimaging data is an exciting prospect in detecting individuals with ASD but further studies are required to improve its reliability for usage in clinical practice.

An Intervention Program Targeting Daily Adaptive Skills Through Executive Function Training for Adults with Autism Spectrum Disorder: A Pilot Study.

OBJECTIVE: Adults with autism spectrum disorders (ASD) experience significant difficulties with executive functioning (EF) and related adaptive skills, yet the lack of interventions in South Korea targeting these areas has resulted in a heightened need to develop an evidence- based program. Therefore, we developed a novel intervention aiming to enhance everyday EF and daily adaptive skills in adults with high-functioning ASD and conducted a pilot study to evaluate the validity and feasibility of the program. METHODS: A behavioral intervention of 10-weekly sessions was developed based on literature searches and focus group interviews. Seven adults with high-functioning ASD (mean age=20.29) participated in a single-group pilot trial. We used self and parent-report questionnaires as well as skills measured by assessment instruments to analyze differences before and after the intervention. RESULTS: Significant improvements were shown in everyday EF, including time management, organization, self-restraint, and regulation of emotions. Additionally, results demonstrated an enhancement in adaptive functioning, especially in the subdomains of daily living skills. Analyses of parental outcomes only revealed a significant decrease in the scores of emotion regulation. CONCLUSION: The current study provides good evidence for the validity and feasibility of an intervention to improve everyday EF and adaptive skills in adults with ASD.

Short caregiver interview and play observation for early screening of autism spectrum disorder: Behavior development screening for toddlers (BeDevel).

This study validates behavior development screening for toddlers (BeDevel), which utilizes a combination of short caregiver interviews (BeDevel-I) and semistructured play observations (BeDevel-P). The data of 431 toddlers (male 66.2%; mean age (SD) = 29.11 (8.59) months; ASD, n = 201; developmental delay, n = 46; typically developing, n = 184), aged 18 ~ 42 months, were included in the validation of BeDevel. The best clinical estimate diagnosis, screening rate, validity, sensitivity, and reliability of BeDevel were determined based on data cross-sectionally collected using BeDevel and existing diagnostic/screening instruments: autism diagnostic observation schedule (ADOS), autism diagnostic interview (ADI-R), Vineland adaptive behavior scales-II (VABS-II), social response scales (SRS), sequenced language scale for infants (SELSI), Korean childhood autism rating scale (K-CARS), and Korean social communication questionnaire (K-SCQ). The k values of BeDevel-I and BeDevel-P were 0.055 ~ 0.732 and 0.291 ~ 0.752, respectively. Items related to social referencing in BeDevel-P had a particularly high diagnostic validity (k = 0.483 ~ 0.684). Reliabilities of BeDevel-I and BeDevel-P were sufficient (Cronbach's alpha = 0.86 ~ 0.88 and 0.92 ~ 0.95, respectively). BeDevel-I and BeDevel-P showed high sensitivity (BeDevel-I: 85.00 ~ 89.29%; BeDevel-P: 85.00 ~ 91.75%), specificity (BeDevel-I: 77.55 ~ 89.55%; BeDevel-P: 85.09 ~ 97.01%), PPV (BeDevel-I: 70.83 ~ 88.54%; BeDevel-P: 81.52 ~ 94.68%), and NPV (BeDevel-I: 76.00 ~ 95.24%; BeDevel-P: 84.62 ~ 95.45%). The agreement between the composite BeDevel score and ADOS, ADI-R, K-CARS, and K-SCQ was >67.6% (range = 67.6 ~ 90.8%). Combining a short caregiver interview and direct play observation is a valid and reliable screening process. More studies on social referencing as an important early marker are needed. BeDevel can be utilized as a secondary screening instrument before diagnostic confirmation in clinical and community settings. LAY SUMMARY: BeDevel, which consists of a short caregiver interview and direct play observation, is a valid and reliable screening instrument for autism spectrum disorder (ASD). We suggest that BeDevel can be utilized as a secondary instrument before administering diagnostic assessments in clinical and community settings. More studies examining social referencing as a potential behavioral marker of ASD are needed.

State and Trait Anxiety of Adolescents with Autism Spectrum Disorders.

OBJECTIVE: This study examined how state and trait anxiety of adolescents with autism spectrum disorders (ASD) are associated with their demographic characteristics, repetitive and restricted behaviors (RRBs), and internalizing and externalizing problem behaviors. METHODS: A total of 96 participants with ASD (mean age=14.30 years; 91 males) completed a battery of tests including the State/Trait Anxiety Inventory (STAI), the Autism Diagnostic Interview-Revised, the Social Responsiveness Scale (SRS), and a cognitive test measuring intelligence quotient (IQ). Participants' parents completed the Child Behavior Checklist (CBCL). Pearson's correlations among age, IQ, two subscales of the STAI (i.e., STAIS and STAIT, measuring self-reported state and trait anxiety, respectively), and the Anxiety subscale of CBCL (i.e., CBCL-Anxiety, measuring parent-reported trait anxiety) were computed. Subsequently, Pearson's correlations were computed among the three anxiety measures, RRBs, and problem behaviors, while controlling for participants' age and IQ. RESULTS: The STAIS and CBCL-Anxiety were both significantly correlated with higher age, sensory sensitivity, depressive symptoms, somatic complaints, and aggressive behaviors. All three anxiety variables were significantly and positively correlated with total SRS RRB scores. Additionally, the STAIS and STAIT were significantly associated with more severe Compulsion/Adherence behaviors, and the CBCL-Anxiety was also significantly associated with more severe Rule-breaking Behaviors. CONCLUSION: Self-reported state anxiety showed association patterns similar to those of parent-reported trait anxiety. Future studies investigating the precise operationalization of different anxiety instruments are needed to accurately measure the anxiety of adolescents with ASD.

Validating the Autism Diagnostic Interview-Revised in the Korean Population.

OBJECTIVE: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). METHODS: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen's kappa. RESULTS: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06-99.27%), specificity (84.75-99.55%), PPV (92.33-99.72%), and NPV (79.43-98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. CONCLUSION: Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.

How Do Children with Autism Spectrum Disorder Encode and Reproduce Visuospatial Stimuli?: Investigation into Visuospatial Processing Abilities and Styles.

OBJECTIVE: The purpose of this study was to examine the visuospatial processing abilities of children with autism spectrum disorder (ASD) using the Rey Osterrieth Complex Figure (ROCF). METHODS: One-hundred thirty-four children with ASD [mean age (MA)=113.56 months], 150 siblings of children with ASD (MA= 111.67 months), and 55 typically developing (TD) children (MA=109.02 months) were included in this study. During their one-time visit, participants completed the ROCF, various autism diagnostic assessments, and the Korean-Leiter International Performance ScaleRevised. Repeated-measures Analysis of Covariance (ANCOVA) and post-hoc Tukey-Kramer comparisons were computed to compare the ROCF scores. Partial correlations and multiple regressions were computed to examine the association between ROCF scores and the severity of autistic symptoms, as measured by the Autism Diagnostic Interview-Revised (ADI-R) among children with ASD. RESULTS: There were significant main effects of the analysis group in Structural and Incidental Accuracy, Error, and Style. More siblings than TD children drew in a part-oriented way, but the performance of the sibling group was comparable or superior to that of the TD group in all parameters. Social Interaction scores of children with ASD were significantly associated with Organization scores in Copy condition. Whether or not a child drew in the Part-Oriented style significantly predicted his/her repetitive and restricted behavior scores. CONCLUSION: The findings add to the evidence for altered visuospatial processing patterns of ASD as a potential inherent and genetic trait and suggest that this particular cognitive style should not be considered as a deficit. Educational and theoretical implications are discussed.

The Use of Artificial Intelligence in Screening and Diagnosis of Autism Spectrum Disorder: A Literature Review.

OBJECTIVES: The detection of autism spectrum disorder (ASD) is based on behavioral observations. To build a more objective datadriven method for screening and diagnosing ASD, many studies have attempted to incorporate artificial intelligence (AI) technologies. Therefore, the purpose of this literature review is to summarize the studies that used AI in the assessment process and examine whether other behavioral data could potentially be used to distinguish ASD characteristics. METHODS: Based on our search and exclusion criteria, we reviewed 13 studies. RESULTS: To improve the accuracy of outcomes, AI algorithms have been used to identify items in assessment instruments that are most predictive of ASD. Creating a smaller subset and therefore reducing the lengthy evaluation process, studies have tested the efficiency of identifying individuals with ASD from those without. Other studies have examined the feasibility of using other behavioral observational features as potential supportive data. CONCLUSION: While previous studies have shown high accuracy, sensitivity, and specificity in classifying ASD and non-ASD individuals, there remain many challenges regarding feasibility in the real-world that need to be resolved before AI methods can be fully integrated into the healthcare system as clinical decision support systems.