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.

Examining the Use of Oral Aripiprazole in Patients With Autism Spectrum Disorder: A Study of Retrospective Chart Review at a University Medical Center.

Objectives: The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at a university medical center in Korea. Methods: We retrospectively reviewed the medical records of 164 outpatient children and adolescents diagnosed with ASD by child and adolescent psychiatrists. Patient demographic characteristics, clinical features, age and dose of aripiprazole treatment, associated adverse events, and concomitant medications, etc. were evaluated. Results: Aripiprazole treatment was initiated at a mean age of 7.64 years, at a mean initial dose of 1.15 mg. Methylphenidate was often co-administered with aripiprazole. The most commonly reported adverse effects were increased appetite and weight gain, which in some cases led to discontinuation of medication. Conclusion: A follow-up study is warranted to evaluate the efficacy and safety of aripiprazole treatment in Korean children and adolescents diagnosed with ASD, and it is crucial to consider their clinical characteristics and response to treatment in the evaluation.

Disparity in the dental care of children and adolescents with autism spectrum disorder in Korea: a national population-based cross-sectional study.

Individuals with autism spectrum disorders (ASD) have difficulty accessing dental care. We aim to verify whether individuals with ASD are properly managed by checking the frequency of dental visits, cost and severity of dental treatment compared with those without ASD. This cross-sectional study used the Korean Health Insurance Database to analyze the frequency, cost and severity of dental treatment in 209,780 people under the age of 19 with or without ASD in 2020. The average frequency of dental visits for individuals without ASD was 2.98 times, which was significantly higher (p < 0.001) than the 2.89 times for those with ASD. However, the average dental cost for individuals with ASD was USD 132.63, which was significantly higher (p < 0.001) than USD 116.57 for those without ASD. Additionally, the average number of times that individuals without ASD received severe dental treatment was 1.23 times, significantly higher than the 1.15 times for those with ASD. Further, per 10,000 people, we found that trauma treatment was recorded for an average of 21.90 individuals with ASD, significantly higher than the 7.75 recorded for those without ASD (p < 0.001). Individuals with ASD encounter significant disparities in accessing dental care, as evidenced by their relatively infrequent dental visits. This discrepancy can be attributed to various barriers including the financial burden compared with those without ASD.

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.

Promoting Self-Efficacy of Individuals With Autism in Practicing Social Skills in the Workplace Using Virtual Reality and Physiological Sensors: Mixed Methods Study.

BACKGROUND: Individuals with autism often experience heightened anxiety in workplace environments because of challenges in communication and sensory overload. As these experiences can result in negative self-image, promoting their self-efficacy in the workplace is crucial. Virtual reality (VR) systems have emerged as promising tools for enhancing the self-efficacy of individuals with autism in navigating social scenarios, aiding in the identification of anxiety-inducing situations, and preparing for real-world interactions. However, there is limited research exploring the potential of VR to enhance self-efficacy by facilitating an understanding of emotional and physiological states during social skills practice. OBJECTIVE: This study aims to develop and evaluate a VR system that enabled users to experience simulated work-related social scenarios and reflect on their behavioral and physiological data through data visualizations. We intended to investigate how these data, combined with the simulations, can support individuals with autism in building their self-efficacy in social skills. METHODS: We developed WorkplaceVR, a comprehensive VR system designed for engagement in simulated work-related social scenarios, supplemented with data-driven reflections of users' behavioral and physiological responses. A within-subject deployment study was subsequently conducted with 14 young adults with autism to examine WorkplaceVR's feasibility. A mixed methods approach was used, compassing pre- and postsystem use assessments of participants' self-efficacy perceptions. RESULTS: The study results revealed WorkplaceVR's effectiveness in enhancing social skills and self-efficacy among individuals with autism. First, participants exhibited a statistically significant increase in perceived self-efficacy following their engagement with the VR system (P=.02). Second, thematic analysis of the interview data confirmed that the VR system and reflections on the data fostered increased self-awareness among participants about social situations that trigger their anxiety, as well as the behaviors they exhibit during anxious moments. This increased self-awareness prompted the participants to recollect their related experiences in the real world and articulate anxiety management strategies. Furthermore, the insights uncovered motivated participants to engage in self-advocacy, as they wanted to share the insights with others. CONCLUSIONS: This study highlights the potential of VR simulations enriched with physiological and behavioral sensing as a valuable tool for augmenting self-efficacy in workplace social interactions for individuals with autism. Data reflection facilitated by physiological sensors helped participants with autism become more self-aware of their emotions and behaviors, advocate for their characteristics, and develop positive self-beliefs.

Diagnosis and Assessment of Autism Spectrum Disorder in South Korea.

Autism spectrum disorder (ASD) is diagnosed by the clinical decision of a trained professional based on the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition or International Classification of Diseases 11th Revision diagnostic criteria. To obtain information for diagnostic formulation, professionals should explore detailed developmental history, and can use structured or semi-structured assessment tools to observe interaction between the child and parents or strangers. Diagnostic assessment should include a profile of the strength and weaknesses of the individual and should be conducted using an optimal approach by a multidisciplinary team with appropriate techniques and experience. Assessment of language, cognitive, neuropsychological, and adaptive functioning should be conducted in ASD individuals prior to establishing an individualized treatment plan. Genetic testing, brain magnetic resonance imaging or electroencephalogram testing can be considered for identification of underlying causes.

A Survey on the Journal of the Korean Academy of Child and Adolescent Psychiatry: Implications for Growth and Development.

Objectives: This study aimed to assess the status of the Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) and propose measures for its growth and development. Methods: The study was conducted using a questionnaire survey targeting members of the Korean Academy of Child and Adolescent Psychiatry. The six key elements analyzed were Access to the journal, Convenience following conversion to English, Recognition as an international journal and institutional achievements, Author perspectives on manuscript submission,Transition to an online-only journal, and Content and identity of the journal. Results: The survey revealed that email notification was highly effective for Journal Accessibility, with the website and search engines also frequently being used by members. Conversion to English in 2018 initially impacted readability and submission rates, but these concerns have decreased over time. However, the Recognition of JKACAP as an international academic journal was still not on par with SCIE journals, highlighting the need for further efforts towards SCIE inclusion. Despite these challenges and limited research opportunities, there was an active intention among members to submit manuscripts. Respondents showed a notable preference for the Transition to an online-only journal. Regarding content and identity of the JKACAP, members predominantly favored review articles and perceived the journal as a research and communication platform for Korean child and adolescent psychiatrists. Conclusion: The results indicate the need for JKACAP to enhance its digital accessibility, provide more support for domestic and international authors, and actively seek SCIE indexing. Addressing the varied content preferences of its members, improving the submission process, and transitioning to an online-only format could further its growth and solidify its position as an internationally recognized academic journal in the field of child and adolescent psychiatry.

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.

Mood and Emotional Changes After PEERS® Program in Parents of Young Adults With Autism Spectrum Disorder.

Objectives: This study examined the changes in anxiety and depressive symptoms in the parents of Korean adults with autism spectrum disorder (ASD) after participating in the Korean version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA-K). Methods: Forty-six parents were enrolled (mean age 54.7 years; 22 fathers and 24 mothers), of whom 27 participated in the PEERS®- YA-K as social coaches. Participants completed self-report scales, including the Test of Young Adult Social Skills Knowledge (TYASSK), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Symptom Check-List-90-R (SCL-90-R). The scales were administered three times: before and after the 16-week program and 4 months after the program ended. Differences between participant variables at pretreatment, post-treatment, and follow-up were analyzed using paired-sample t-tests. Results: Participants showed a significant improvement in their social skills knowledge (TYASSK) (p<0.01). There was a significant improvement in the BAI and BDI scores of parents with severe depressive and anxiety symptoms at the baseline (p<0.05). Paternal paranoia and maternal hostility results also significantly improved on the SCL-90-R. Conclusion: This study suggests that PEERS®-YA-K can reduce parental anxiety and depressive symptoms. To the best of our knowledge, this is the first to compare the degree of depression and anxiety after PEERS®-YA-K in parents of adults with ASD.

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.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

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.