1. Capiotto F, Romano Cappi G, Mirlisenna I, Mazza A, Cicinelli G, Lauritano C, Keller R, Dal Monte O. Autonomic and hedonic response to affective touch in autism spectrum disorder. Autism Res. 2024.

Interpersonal touch plays a crucial role in shaping relationships and encouraging social connections. Failure in processing tactile input or abnormal tactile sensitivity may hamper social behaviors and have severe consequences in individuals’ relational lives. Autism Spectrum Disorder (ASD) is characterized by both sensory disruptions and social impairments, making affective touch an ideal meeting point for understanding these features in ASD individuals. By integrating behavioral and physiological measures, we investigated the effects of affective touch on adult individuals with ASD from both an implicit and explicit perspective. Specifically, at an implicit level, we investigated whether and how receiving an affective touch influenced participants’ skin conductance tonic and phasic components. At the explicit level, we delved into the affective and unpleasant features of affective touch. Overall, we observed lower skin conductance level in ASD compared to TD subjects. Interestingly, the typically developing (TD) group showed an increased autonomic response for affective touch compared to a control touch, while ASD subjects’ autonomic response did not differ between the two conditions. Furthermore, ASD participants provided higher ratings for both the affective and unpleasant components of the touch, compared to TD subjects. Our results reveal a noteworthy discrepancy in ASD population between the subjective experience, characterized by amplified hedonic but also unpleasant responses, and the physiological response, marked by a lack of autonomic activation related to affective touch. This insightful dissociation seems crucial for a deeper understanding of the distinctive challenges characterizing people with ASD and may have implications for diagnosis and therapeutic approaches.

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2. Denusik L, Glista D, Servais M, Friesen J, Oram J, Cunningham BJ. « We were the best people to do the job »: Caregivers’ reported outcomes of a virtual caregiver-delivered program for autistic preschoolers. Autism Dev Lang Impair. 2024; 9: 23969415241244767.

BACKGROUND AND AIMS: Caregiver-delivered programs are a recommended best practice to support young autistic children. While research has extensively explored children’s outcomes quantitatively, minimal qualitative research has been conducted to understand caregivers’ perspectives of program outcomes for themselves and their children. Hearing directly from caregivers is an important step in ensuring these programs are meeting the needs of those who use them. This study explored caregivers’ perceived outcomes following one virtual caregiver-delivered program, The Hanen Centre’s More Than Words(®) (MTW) program. METHODS: This study was a secondary analysis of data from individual interviews conducted with 21 caregivers who had recently participated in a virtual MTW program. A hybrid codebook thematic analysis approach was taken to analyze the interview data. Program outcomes were coded and analyzed within the International Classification Functioning, Disability, and Health (ICF) framework. Additionally, caregivers completed an online survey and rated Likert Scale items about perceived program outcomes, which were analyzed descriptively. RESULTS: Five themes were identified: (1) caregivers learned new strategies to facilitate their child’s development, (2) caregivers developed a new mindset, (3) children gained functional communication skills, (4) caregiver-child relationships improved, and (5) caregivers gained a social and professional support network. These themes fell within four of five ICF framework components (activities, participation, personal factors, and environmental factors). No themes were identified under Body Structures and Functions. Survey results indicated most caregivers reported learning new communication strategies (n = 20, 95%), and identifying new teaching opportunities with their child (n = 21, 100%). CONCLUSIONS: Some reported outcomes, related to Activities and Participation, were consistent with previous reports in the literature on the MTW program. In line with previous research, caregivers learned strategies to support their child’s communication development. Contrary to previous quantitative studies, caregivers in this study rarely commented on gains in vocabulary and instead focused on gains in skills that positively impacted their child’s ability to engage in meaningful social interaction. Novel outcomes were identified within the Participation, Personal Factors, and Environmental Factors components of the ICF framework. IMPLICATIONS: Caregivers in this study identified important outcomes for themselves and their child that have not been the focus of prior research, suggesting it is important to integrate their perspectives in the development and evaluation of caregiver-delivered programs. Clinicians should include goals that address outcomes identified as important by caregivers, including those that address children’s Participation, and those that target caregivers’ Personal and Environmental Factors. Developers of caregiver-delivered programs could integrate identified goals to ensure they are meeting families’ needs.

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3. Duan S, Yue F, Yang X, Liu R, He J. [Preimplantation genetic testing for a Chinese pedigree affected with Rett syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024; 41(5): 526-32.

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT). METHODS: A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies. RESULTS: PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c.925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term. CONCLUSION: NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

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4. He W, Zhang W, Jin Y, Zhou Q, Zhang H, Xia Q. Physician Versus Large Language Model Chatbot Responses to Web-Based Questions From Autistic Patients in Chinese: Cross-Sectional Comparative Analysis. J Med Internet Res. 2024; 26: e54706.

BACKGROUND: There is a dearth of feasibility assessments regarding using large language models (LLMs) for responding to inquiries from autistic patients within a Chinese-language context. Despite Chinese being one of the most widely spoken languages globally, the predominant research focus on applying these models in the medical field has been on English-speaking populations. OBJECTIVE: This study aims to assess the effectiveness of LLM chatbots, specifically ChatGPT-4 (OpenAI) and ERNIE Bot (version 2.2.3; Baidu, Inc), one of the most advanced LLMs in China, in addressing inquiries from autistic individuals in a Chinese setting. METHODS: For this study, we gathered data from DXY-a widely acknowledged, web-based, medical consultation platform in China with a user base of over 100 million individuals. A total of 100 patient consultation samples were rigorously selected from January 2018 to August 2023, amounting to 239 questions extracted from publicly available autism-related documents on the platform. To maintain objectivity, both the original questions and responses were anonymized and randomized. An evaluation team of 3 chief physicians assessed the responses across 4 dimensions: relevance, accuracy, usefulness, and empathy. The team completed 717 evaluations. The team initially identified the best response and then used a Likert scale with 5 response categories to gauge the responses, each representing a distinct level of quality. Finally, we compared the responses collected from different sources. RESULTS: Among the 717 evaluations conducted, 46.86% (95% CI 43.21%-50.51%) of assessors displayed varying preferences for responses from physicians, with 34.87% (95% CI 31.38%-38.36%) of assessors favoring ChatGPT and 18.27% (95% CI 15.44%-21.10%) of assessors favoring ERNIE Bot. The average relevance scores for physicians, ChatGPT, and ERNIE Bot were 3.75 (95% CI 3.69-3.82), 3.69 (95% CI 3.63-3.74), and 3.41 (95% CI 3.35-3.46), respectively. Physicians (3.66, 95% CI 3.60-3.73) and ChatGPT (3.73, 95% CI 3.69-3.77) demonstrated higher accuracy ratings compared to ERNIE Bot (3.52, 95% CI 3.47-3.57). In terms of usefulness scores, physicians (3.54, 95% CI 3.47-3.62) received higher ratings than ChatGPT (3.40, 95% CI 3.34-3.47) and ERNIE Bot (3.05, 95% CI 2.99-3.12). Finally, concerning the empathy dimension, ChatGPT (3.64, 95% CI 3.57-3.71) outperformed physicians (3.13, 95% CI 3.04-3.21) and ERNIE Bot (3.11, 95% CI 3.04-3.18). CONCLUSIONS: In this cross-sectional study, physicians’ responses exhibited superiority in the present Chinese-language context. Nonetheless, LLMs can provide valuable medical guidance to autistic patients and may even surpass physicians in demonstrating empathy. However, it is crucial to acknowledge that further optimization and research are imperative prerequisites before the effective integration of LLMs in clinical settings across diverse linguistic environments can be realized. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300074655; https://www.chictr.org.cn/bin/project/edit?pid=199432.

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5. K CR, Tiemroth AS, Thurmon AN, Meadows SM, Galazo MJ. Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability. Front Psychiatry. 2024; 15: 1375492.

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers. Importantly, de novo mutations are emerging as important contributors to NDDs and neuropsychiatric disorders. Recently, de novo mutations in transcriptional co-factor Zmiz1 or its regulatory regions have been identified in unrelated patients with syndromic ID and ASD. However, the role of Zmiz1 in brain development is unknown. Here, using publicly available databases and a Zmiz1 mutant mouse model, we reveal that Zmiz1 is highly expressed during embryonic brain development in mice and humans, and though broadly expressed across the brain, Zmiz1 is enriched in areas prominently impacted in ID and ASD such as cortex, hippocampus, and cerebellum. We investigated the relationship between Zmiz1 structure and pathogenicity of protein variants, the epigenetic marks associated with Zmiz1 regulation, and protein interactions and signaling pathways regulated by Zmiz1. Our analysis reveals that Zmiz1 regulates multiple developmental processes, including neurogenesis, neuron connectivity, and synaptic signaling. This work paves the way for future studies on the functions of Zmiz1 and highlights the importance of combining analysis of mouse models and human data.

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6. Kata A, McPhee PG, Chen YJ, Zwaigenbaum L, Singal D, Roncadin C, Bennett T, Carter M, Di Rezze B, Drmic I, Duku E, Fournier S, Frei J, Gentles SJ, Georgiades K, Hanlon-Dearman A, Hoult L, Kelley E, Koller J, de Camargo OK, Lai J, Mahoney B, Mesterman R, Ng O, Robertson S, Rosenbaum P, Salt M, Zubairi MS, Georgiades S. The Pediatric Autism Research Cohort (PARC) Study: protocol for a patient-oriented prospective study examining trajectories of functioning in children with autism. BMJ Open. 2024; 14(4): e083045.

INTRODUCTION: The developmentally variable nature of autism poses challenges in providing timely services tailored to a child’s needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child’s day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning. METHODS AND ANALYSIS: We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child's progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school. ETHICS AND DISSEMINATION: Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals.

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7. Lin P, Feng X, Hao S, Jia C, Pan H, Zhang C, Hui L, Zhang Q. [Clinical and molecular genetic analysis of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024; 41(5): 612-6.

OBJECTIVE: To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT). METHODS: A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject. Clinical data of the infant was collected. Genomic DNA was extracted from peripheral blood samples from the infant and his parents, and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 4-day-old male infant, had presented with poor response, poor intake, feeding difficulties, and deceased at 8 months after birth. WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region, which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA, CORO1A, KIFF22, PRRT2 and TBX6. His father has carried the same deletion, but was phenotypically normal. The deletion was predicted to be pathogenic. The child was also found to harbor a maternally derived c.763C>T (p.R255X) hemizygous variant of the MECP2 gene, which was also predicted to be pathogenic (PVS1+PS4+PM2_Supporting). CONCLUSION: The 16p11.2 deletion and the MECP2: c.763C>T (p.R255X) variant probably underlay the pathogenesis in this infant.

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8. Margari A, De Agazio G, Marzulli L, Piarulli FM, Mandarelli G, Catanesi R, Carabellese FF, Cortese S. Autism spectrum disorder (ASD) and sexual offending: a systematic review. Neurosci Biobehav Rev. 2024: 105687.

The relationship between autism spectrum disorder (ASD) and sexual offending (SO) is an overlooked issue, both in clinical practice and in research. Based on a pre-specified protocol (PROSPERO: CRD42024501598), we systematically searched Pubmed and Scopus, between January 1(st), 1994 and January 12(th), 2024, for articles related to SO in ASD. Study quality was assessed with study design-specific tools (Study Quality Assessment Tools, NHLBI, NIH). We found 19 relevant publications (five cross-sectional studies, two case-control studies, and 12 case reports). Seven of the studies were deemed of « good » quality, the rest as « fair ». Included studies addressed three key aspects: 1) psychopathological characteristics of individuals with ASD that increase the risk of committing SO; 2) intervention strategies for individuals with ASD and SO; 3) involvement of individuals with ASD and SO in the justice system. Overall, while there is an increasing interest in this topic, more rigorous study designs, including randomised controlled trials, are needed to inform clinical practice and healthcare and social policies.

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9. Robinson K, Jamison J. Teaching Physician Assistant Students to Care for People With Intellectual and Developmental Disabilities. J Physician Assist Educ. 2024.

The purposes of this educational activity were to instill in students a greater empathy for patients with intellectual developmental disabilities, give students a better understanding of how to obtain a medical history for patients with communication limitations, teach students practical tips for obtaining a medical history and physical examination to increase competence in their future practice, and to build a relationship with a local organization that serves people with intellectual disabilities. An experiential learning activity was added to the curriculum of two courses for first-year PA students to accomplish these goals. The course instructors engaged in several planning meetings with a local residential facility for people with intellectual disabilities, including choosing patients that the students would assess. The students made 3 visits to the facility. The visits included interactive lectures by a physical therapist, occupational therapist, nurse practitioner, medical doctor, and dentist. Two of the facility involved patient visits at designated homes on campus. The students then wrote comprehensive visit notes with patient identifying information removed and submitted them for grading. Students expressed feeling better prepared to assess people with intellectual disabilities and having an increased appreciation for obtaining quality medical histories. The partner facility also reported they received positive feedback from staff participants and indicated they would like to continue this partnership.

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10. Schwarz M, Geryk J, Havlovicová M, Mihulová M, Turnovec M, Ryba L, Martinková J, Macek M, Jr., Palmer R, Kočandrlová K, Velemínská J, Moslerová V. Body mass index is an overlooked confounding factor in existing clustering studies of 3D facial scans of children with autism spectrum disorder. Sci Rep. 2024; 14(1): 9873.

Cluster analyzes of facial models of autistic patients aim to clarify whether it is possible to diagnose autism on the basis of facial features and further to stratify the autism spectrum disorder. We performed a cluster analysis of sets of 3D scans of ASD patients (116) and controls (157) using Euclidean and geodesic distances in order to recapitulate the published results on the Czech population. In the presented work, we show that the major factor determining the clustering structure and consequently also the correlation of resulting clusters with autism severity degree is body mass index corrected for age (BMIFA). After removing the BMIFA effect from the data in two independent ways, both the cluster structure and autism severity correlations disappeared. Despite the fact that the influence of body mass index (BMI) on facial dimensions was studied many times, this is the first time to our knowledge when BMI was incorporated into the faces clustering study and it thereby casts doubt on previous results. We also performed correlation analysis which showed that the only correction used in the existing clustering studies-dividing the facial distance by the average value within the face-is not eliminating correlation between facial distances and BMIFA within the facial cohort.

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11. Tamon H, Fujino J, Itahashi T, Frahm L, Parlatini V, Aoki YY, Castellanos FX, Eickhoff SB, Cortese S. Shared and Specific Neural Correlates of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Meta-Analysis of 243 Task-Based Functional MRI Studies. Am J Psychiatry. 2024: appiajp20230270.

OBJECTIVE: To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. METHODS: A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis. RESULTS: After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively. CONCLUSIONS: Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.

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12. Tirupathi SP, Afnan L. Effect of Sensory Adapted Dental Environment (SADE) on physiological and behavioral parameters related to stress and anxiety in children with Autism Spectrum Disorder (ASD) undergoing dental treatment: A systematic review and meta-analysis. Spec Care Dentist. 2024.

BACKGROUND: Children with autism exhibit a higher general and dental anxiety, due to altered sensory sensibilities. AIM: This current systematic review aims to evaluate the effectiveness of Sensory adapted dental environment (SADE) over regular dental environment (RDE) on behavioral, physiological stress and overt anxiety in children with autism spectrum disorders (ASDs). MATERIALS AND METHODS: Prospero registered (CRD42024508336). PubMed, Cochrane, Scopus databases are searched from years January 1, 1980-January 1, 2024 using pre-defined search strategy. RESULTS: A total of 269 titles, were obtained from the included databases after application of filters, exclusion of duplicates and reviews and irrelevant articles led to the final inclusion of 12 articles for full text screening from which, three studies sustained the targeted PICO search. CONCLUSION: Skin conductance level (parameter indicating physiological stress) is lower in SADE environment in children with ASD, other behavior stress related parameters there is no significant difference between SADE and RDE environments.

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13. Zhang Y, Chen Z, Wang J, Wei G, Niu J, Wang Y, Wang H. [Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024; 41(5): 591-5.

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay. METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c.2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+PM2_Supporting+PP1+PP3). CONCLUSION: The c.2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.

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