1. Albright J, Shinall JA, Tomczuk L, Stewart RE, Mandell DS, Stahmer AC, Beidas RS, Pellecchia M. A multi-constituent qualitative examination of facilitators and barriers to caregiver coaching for autistic children in publicly funded early intervention. Autism;2024 (Aug 22):13623613241272993.

Caregiver coaching is an evidence-based practice for young autistic children, but it is not widely used in community-based early intervention services. Previous research has explored why caregiver coaching is not widespread in early intervention, but only from the perspective of early intervention providers. Caregivers, providers, and administrators are all involved in the decision of whether to use caregiver coaching in early intervention. Therefore, it is important to include all perspectives in research regarding this practice. In this study we interviewed 20 caregivers of autistic children, 36 early intervention providers, and 6 administrators from early intervention agencies and asked questions about their perspectives regarding the use of caregiver coaching in early intervention. We did this to figure out what factors help and hinder the use of caregiver coaching in this setting and to see how caregivers, providers, and administrators agreed or disagreed on these factors. All participants agreed that caregivers’ attitudes and expectations can influence whether caregiver coaching is used. In addition, all participants agreed that when caregivers and providers collaborate and have a strong working relationship, it can facilitate the use of caregiver coaching in early intervention. Other factors, such as caregiver stress and provider flexibility were also discussed. Based on these findings, we suggest strategies that can be used to possibly increase the use of caregiver coaching in early intervention for autistic children and their families.

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2. Ansoborlo M, Gaudichon V, Hazard M, Zopppe H, Defresne D, Guinoiseau K, Salpetrier C, Grammatico-Guillon L, Bonnet-Brilhault F. Coordination and Referral Platforms for Children Aged 7 and Under with Suspected Neurodevelopmental Outcome: What Data for Research on Care and Developmental Trajectories?. Stud Health Technol Inform;2024 (Aug 22);316:1955-1959.

At the core of the child’s medical, social, and educational pathway, coordination and referral platforms (CRPs) for neurodevelopmental disorders (NDDs) have been gradually deployed in France since 2018 and support the early detection of NDDs in children. The 112 nationwide CRPs do not benefit from a common electronic health record system. Our aim was to propose an HER model for CRP to enable real-life data reuse, optimize care pathway management and conduct pre-screening for research. CRP data were collected (n=34) into an application enriched by a NLP tool extracting standardized scales for NDDs assessments from medical and paramedical professionals. NLP tool evaluation presented a precision of 86.4% and recall of 90.5%. CRP support was provided to 195 children included between 1 September 2022 and 31 August 2023, aged 4 years, with a sex ratio of 2.8, with delays reported in language (75%) and concerned by global developmental delays (16%). Children’s ND phenotype and care pathway description could be automated by a harmonized and structured EHR. While many clinical situations are at an impasse, real-life data-driven evidence is particularly relevant in the context of NDDs, where early intervention plays such a key role in children’s development and prognosis. A harmonized and enriched CRP database could benefit both individual and public health levels with pathway monitoring, intervention proposals and research pre-screenings.

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3. Berg Egge HS, Gabarron E. TikTok and YouTube Shorts by Autistic Individuals for Increasing Autism Awareness. Stud Health Technol Inform;2024 (Aug 22);316:1891-1895.

INTRODUCTION: Autistic individuals, parents, organizations, and healthcare systems worldwide are actively sharing content aimed at increasing awareness about autism. This study aims at analyzing the type of contents presented in TikTok and YouTube Shorts videos under the hashtag #actuallyautistic and their potential to increase autism awareness. METHODS: A sample of 60 videos were downloaded and analyzed (n=30 from TikTok and n=30 from YouTube Shorts). Video contents were analyzed using both thematic analysis and the AFINN sentiment analysis tool. The understandability and actionability of the videos were assessed with The Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT A/V). RESULTS: The contents of these videos covered five main themes: Stigmatization; Sensory difficulties; Masking; Stimming; and Communication difficulties. No statistically significant differences were found on sentiment expressed on videos from both channels. TikTok videos received significantly more views, comments, and likes than videos on YouTube Shorts. The PEMAT A/V tool showed that there is a high level of understandability, but little reference to actionability. DISCUSSION: Autistic people videos content spread valid and reliable information in hopes of normalizing difficulties and provide hope and comfort to others in similar situations. CONCLUSIONS: Social media videos posted by autistic individuals provide accurate portrayals about autism but lack information on actionability. These shared personal stories can help increase public literacy about autism, dispel autism stigmas and emphasize individuality.

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4. Brown CE, Bernardin CJ, Beauchamp MT, Kanne SM, Nowell KP. More similar than different: Characterizing special interests in autistic boys and girls based on caregiver report. Autism Res;2024 (Aug 22)

Almost all autistic youths have special interests (SIs), which are focused, intense areas of passion and interest in a particular topic. Emerging research suggests that there are gender differences in SIs among autistic youth; however, commonly used measures that assess for the presence of SIs may not fully capture the granular nature of those differences between autistic boys and girls. Characterizing these differences is important for autism identification in girls, as SIs in autistic girls may often be overlooked by caregivers, teachers, and clinicians due to their more « typical » and more socially oriented content areas compared to autistic boys. This study therefore aimed to more fully characterize gender differences in SIs using a newly developed caregiver-report measure of SIs (the Special Interests Survey; SIS). Caregivers of 1921 autistic youth completed the SIS. Analyses revealed many similarities between boys and girls; there were no gender differences in mean age SI onset, caregivers’ perceptions of uniqueness or interferences of endorsed SIs, or duration of previous SIs. There were gender differences in endorsement of less than half (39%) of the SI categories measured, and there were minor differences in the number of endorsed current and past SIs. Categories with significant gender differences fell along typical gender lines (e.g., more boys interested in math and construction, more girls interested in animals and arts/crafts). This study extends the growing literature on SIs and gender differences in autism and has important implications for supporting autistic youth and their families.

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5. Dimitriou D, Khan YS, Khan AW, Esposito G. Editorial: Advancing understanding and care for individuals with developmental disabilities in the Middle East. Res Dev Disabil;2024 (Aug 22);153:104816.

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6. Duan X, Shan X, Uddin LQ, Chen H. The future of disentangling the heterogeneity of autism with neuroimaging studies. Biol Psychiatry;2024 (Aug 22)

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition. Over the past decade, a considerable number of approaches have been developed to identify potential neuroimaging-based biomarkers of ASD and have uncovered specific neural mechanisms underlying behaviors associated with ASD. However, the substantial heterogeneity among those diagnosed with ASD hinders the development of biomarkers. Disentangling the heterogeneity of ASD is pivotal to improve quality of life for individuals with ASD by facilitating early diagnosis and individualized interventions for those who need support. In this Review, we discuss recent advances in neuroimaging that have facilitated the characterization of the heterogeneity of this condition from three frameworks: neurosubtyping, dimensional models, and normative models. In addition, we discuss the challenges, possible solutions, and clinical utility of these three frameworks. We argue that several factors need to be considered when parsing heterogeneity using neuroimaging, including co-occurring conditions, neurodevelopment, heredity and environment, and multi-site and multi-modality data. We close with a discussion of future directions for achieving a better understanding of the neural mechanisms underlying neurodevelopmental heterogeneity and the future of precision medicine in ASD.

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7. Folz J, Nikolić M, Kret ME. Individual differences in interoception and autistic traits share altered facial emotion perception, but not recognition per se. Sci Rep;2024 (Aug 21);14(1):19455.

While alterations in both physiological responses to others’ emotions as well as interoceptive abilities have been identified in autism, their relevance in altered emotion recognition is largely unknown. We here examined the role of interoceptive ability, facial mimicry, and autistic traits in facial emotion processing in non-autistic individuals. In an online Experiment 1, participants (N = 99) performed a facial emotion recognition task, including ratings of perceived emotional intensity and confidence in emotion recognition, and reported on trait interoceptive accuracy, interoceptive sensibility and autistic traits. In a follow-up lab Experiment 2 involving 100 participants, we replicated the online experiment and additionally investigated the relationship between facial mimicry (measured through electromyography), cardiac interoceptive accuracy (evaluated using a heartbeat discrimination task), and autistic traits in relation to emotion processing. Across experiments, neither interoception measures nor facial mimicry accounted for a reduced recognition of specific expressions with higher autistic traits. Higher trait interoceptive accuracy was rather associated with more confidence in correct recognition of some expressions, as well as with higher ratings of their perceived emotional intensity. Exploratory analyses indicated that those higher intensity ratings might result from a stronger integration of instant facial muscle activations, which seem to be less integrated in intensity ratings with higher autistic traits. Future studies should test whether facial muscle activity, and physiological signals in general, are correspondingly less predictive of perceiving emotionality in others in individuals on the autism spectrum, and whether training interoceptive abilities might facilitate the interpretation of emotional expressions.

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8. Fusar-Poli L, Avanzato C, Maccarone G, Di Martino E, Avincola G, Grasso S, Rapisarda G, Guarnieri F, Signorelli MS. The Association between Attention-Deficit-Hyperactivity Disorder and Autistic Traits with Psychotic-like Experiences in Sample of Youths Who Were Referred to a Psychiatric Outpatient Service. Brain Sci;2024 (Aug 22);14(8)

The aim of this study is to identify autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) traits in adolescents who experience psychotic-like experiences (PLEs), often ignored in clinical practice but widely prevalent in the general population. A total of 57 adolescents and young adults (aged between 16 and 24 years old) were recruited consecutively in the outpatient services. A total of 37 were females (64.9%), 18 were males (31.6%), and two participants (3.5%) were non-binary or gender non-conforming, with a mean age at referral of 18.26 ± 2.06. To investigate these symptoms, three sets of standardized questionnaires were used, as follows: the Autism Spectrum Quotient-short form (AQ-10), the Community Assessment of Psychic Experiences (CAPE-42), and the Adult ADHD Self-Report Scale (ASRS). We found significant associations between the ASRS and AQ-10 total scores and all CAPE scales. The model which explained the highest variance was CAPE Score’s Total Frequency score (p < 0.001). Our findings underline the importance of investigating the presence of subthreshold ASD and ADHD symptoms in clinical populations, particularly in the period of adolescence and young adulthood, to promptly identify the presence of PLEs and, thus, prevent the onset of a frank psychotic disorder, particularly in the presence of a comorbid psychopathological condition, leading to better diagnosis and treatment for individuals with two or more of these conditions.

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9. Gabarron E, Dorronzoro E, Rivera-Romero O, Denecke K. Understanding Emotional Dynamics in Autism Social Media Communities. Stud Health Technol Inform;2024 (Aug 22);316:1901-1905.

Searches for autism on social media have soared, making it a top topic. Social media posts convey not only plain text, but also sentiments and emotions that provide insight into the experiences of the autism community. While sentiment analysis categorizes overall sentiment, emotion analysis provides nuanced insights into specific emotional states. The objective of this study is to identify emotions in posts related to autism and compare the emotions specifically contained in posts that include the hashtag #ActuallyAutistic with those that do not. METHODS: We extracted a sample of X’ posts related to autism and used DistilBERT to assign one out of six emotions (sadness, joy, love, anger, fear, surprise) to each post. RESULTS: We have analyzed a total of 414,287 posts, 98,602 (23.8%) of those included the hashtag #ActuallyAutistic. The most common expressed emotion was joy, which was expressed in 52.5% of the posts, followed by sadness, identified in 28.6% of the posts. 12% of the posts expressed fear, 4.9% reflected anger, 1.1% showed love, and 0.9% expressed surprise. Posts tagged as #ActuallyAutistic showed less joy (27.1% vs. 60.4% in posts without this hashtag, p<0.001) and more sadness (52.7% vs. 21.1% in those without the hashtag, p<0.001). CONCLUSIONS: The use of the hashtag #ActuallyAutistic is associated with a different emotional tone, characterized by less joy and more sadness. These results suggest the need for greater support and acceptance towards the autistic community, both online and in society in general. Insights from our study can be valuable for policy makers, health, educational or other programmes aiming at enhancing well-being, inclusiveness, improve services, and create a more compassionate and understanding atmosphere for autistic people.

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10. Gulati S, Kamila G, Hameed B, Newton CR. Brushing away barriers: The healing touch of art as an intervention in children with autism. Autism;2024 (Aug 22):13623613241274845.

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11. Hsiao MN, Chien YL, Tai YM, Chen HM, Shih HH, Chen LW, Chen YY, Soong WT, Chiu YN, Tsai WC, Laugeson E, Tseng MH, Gau SS. A preliminary randomized controlled study of the PEERS® program for Taiwanese autistic adolescents: The effectiveness on reducing school bullying and enhancing social function. Autism Res;2024 (Aug);17(8):1705-1720.

Individuals with autism spectrum disorder (ASD) often experience lifelong social communication challenges and are more vulnerable to school bullying. Addressing their social difficulties and school bullying requires evidence-based interventions. PEERS® (Program for the Education and Enrichment of Relational Skills) was adapted and translated for Taiwanese adolescents. This randomized controlled study aimed to examine the effectiveness of the Taiwanese version of PEERS® in reducing school bullying and enhancing social function among autistic adolescents. Twenty-one autistic adolescents (mean age 14.29 ± 1.67 years; female n = 733.33%) were randomized to a treatment group (TG, n = 10) or a delayed treatment control group (DTG, n = 11). The outcome measures (school bullying, social challenges, social skills knowledge, and social skills performance) were assessed at baseline, post-treatment, and follow-up. The group and time interaction analyses revealed greater magnitudes of reduction in general school bullying (p < 0.001), victimization (p < 0.001), perpetration (p = 0.012), social challenges (p = 0.001), and peer conflicts (p < 0.001), and improvement in social knowledge (p < 0.001) in the TG group than the DTG group. The findings suggest that the PEERS® program tailored for Taiwanese adolescents is effective in reducing school bullying, decreasing social challenges, and enhancing social skills among autistic adolescents, with very large effect sizes (Cohen's d ranging from 1.19 to 2.88). Consequently, participation in the PEERS® program is recommended for adolescents with social difficulties to improve their social communication and interactions to offset school bullying and other social challenges related to adverse outcomes.

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12. Hull L, Mandy W, Belcher H, Petrides KV. Validation of the camouflaging autistic traits questionnaire short form (CATQ-SF). Compr Psychiatry;2024 (Aug 22);135:152525.

BACKGROUND: Camouflaging of autistic traits involves hiding or compensating for autistic characteristics, often due to stigma or a desire to fit in with others. This behaviour has been associated with mental health issues in autistic individuals. The 2 5-item Camouflaging Autistic Traits Questionnaire (CAT-Q) is the most commonly used self-report measure of camouflaging. In this study, a 9-item short form version was developed for use in clinical and research settings. AIMS: To construct and psychometrically validate a brief self-report measure of camouflaging. METHOD: The Camouflaging Autistic Traits Questionnaire – Short Form (CATQ-SF) was developed and its factor structure and psychometric properties were evaluated in two studies. Study 1 used a large, online sample of autistic and non-autistic adults (N = 832) to evaluate the factor structure, psychometric properties, and measurement invariance of the CATQ-SF. Study 2 used an independent sample of autistic and non-autistic adults (N = 80) to test Study 1’s findings. RESULTS: In Study 1, evidence for a three-factor structure was observed, with good internal consistency (combined autistic & non-autistic α = 0.84). In addition, the instrument demonstrated measurement invariance, and reliably predicted higher levels of autistic traits. In Study 2, the 3-factor structure was replicated, and good internal consistency was again observed (combined autistic and non-autistic α = 0.89). In both studies, psychometric properties were of similar or higher validity compared to the full-form CAT-Q. CONCLUSIONS: The CATQ-SF can be used by clinicians and researchers to measure camouflaging in autistic and non-autistic adults quickly and reliably.

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13. Ikeda A, Hakuno Y, Asada K, Ikeda T, Yamagata T, Hirai M. Developmental process of the understanding of linguistic register in children: A comparison of typically developing children, autistic children, and children with Williams syndrome. Autism Res;2024 (Aug 21)

Although the developmental process of linguistic register-the appropriate manner of speech as determined by the listener and social situation-has been gradually clarified in typically developing (TD) children, research on the mechanism and developmental process of register acquisition in atypically developing children are insufficient. This study compared the developmental process of understanding linguistic register among TD children, autistic children, and those with Williams syndrome (WS), and examined the contributions of social cognition and motivation to the acquisition of linguistic register. Two experiments were designed to assess the recognition of which linguistic register to use when communicating with different listeners and of the listener’s feelings according to the speakers’ use of register. The results revealed that the process of understanding register-listener associations was nearly identical among all groups of children and their understanding improved with age. Conversely, their understanding of the effect of register selection on the listener’s feelings varied. Importantly, as TD children mature, they become aware that adult listeners may feel negatively when spoken to in an inappropriate register, whereas autistic children and those with WS do not exhibit the same awareness. Thus, our results suggest that atypical social cognition and motivation do not disturb the understanding of register-listener associations. However, social cognition and motivation play important roles in understanding the effect of register selection on the listener’s feelings. These findings provide a significant contribution to clarifying the mechanism of linguistic register acquisition.

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14. Li Y, Gu J, Li R, Yi H, He J, Gao J. Sensory and motor cortices parcellations estimated via distance-weighted sparse representation with application to autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Aug 22);135:111125.

BACKGROUND: Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. METHODS: Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. RESULTS: We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). LIMITATIONS: The generalizability of the segmentation model requires further evaluation. CONCLUSIONS: This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD.

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15. Maleki Z, Heidarabadi S, Mohammadi A, Azami-Aghdash S, Rosenbaum P, Cross A, Soper AK. Disseminating the F-Words for Child Development to Parents of Children With Developmental Disabilities in Iran: A Qualitative Pilot Feasibility Study. Child Care Health Dev;2024 (Sep);50(5):e13321.

BACKGROUND: Attitudes toward childhood disability have historically focused on biomedical efforts on ‘fixing’. The introduction of WHO’s ICF framework for health and Canadian researchers’ ‘F-words’ (functioning, fitness, fun, friends, family and future) have significantly changed the field. To explore whether the F-words ideas influenced parents’ perspectives on their child’s abilities and rehabilitation goals, this qualitative pilot study introduced the F-words to Iranian parents with a child with a developmental disability. METHODS: This study was conducted in Tabriz, Iran, in 2023, using Iranian educational F-words materials built on ideas available on the CanChild F-words Knowledge Hub. Data were collected through semistructured interviews with five mothers of children <5 years old with a developmental disability before and after attending an 'F-words Awareness Session' and analysed using thematic analysis. RESULTS: In the preinterviews, six themes (and 20 subthemes) were identified: (i) routines (5); (ii) challenges (4); (iii) parental concerns (3); (iv) child's needs and priorities (3); (v) the role of parents in satisfying needs and challenges (2); and (vi) expectations of rehabilitation (3). In the postinterview, the same six themes and four additional subthemes emerged. CONCLUSION: Findings from the pilot study showed that the intervention had an impact on the attitudes and behaviours of participants. Specifically, teaching about the F-words reduced parents' emphasis on the concept of 'normality'. Families' positive response to the 'F-words Awareness Session' indicates their openness to incorporating this approach into their daily lives. These findings highlight the potential benefits of utilizing the F-words in rehabilitation in Iran. Studies like these can serve as a foundation for developing effective strategies for integrating the F-words into existing rehabilitation practices in Iran.

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16. McNally Keehn R, Paxton A, Delaney M, Ciccarelli M. Training and Sustaining: Training and Learning Collaborative Outcomes Across a Statewide Network for Early Autism Diagnosis. J Dev Behav Pediatr;2024 (Aug 22)

OBJECTIVE: The objective of this study was to describe the development of a primary care professional (PCP) autism diagnosis training model and to report on outcomes related to PCP training and sustained engagement in a longitudinal learning collaborative. METHODS: We developed Accelerating the Diagnosis of Autism with Primary care Training (ADAPT), a training program to prepare PCPs to develop independent competency in evaluation of autism in children aged 14 to 48 months. ADAPT includes didactic and case-based modules and practice-based coaching delivered by an expert diagnostic specialist; after training, PCPs participate in a longitudinal learning collaborative. Aligned with competency-based medical education standards, measures of autism evaluation knowledge and diagnostic competency are collected. RESULTS: From 2021 to 2023, 13 PCPs completed ADAPT didactic and practicum training to reach competency in independent autism evaluation. Clinicians demonstrated significant improvement in total autism knowledge after didactic training (p = 0.02). Scoring agreement on an autism observational assessment tool between clinicians and expert diagnosticians improved over case observations and practicum evaluations. Similarly, PCPs demonstrated improved evaluation competence, moving on average from Advanced Beginner to Competent Performer as rated by expert diagnosticians. After training, PCPs attended 57% of monthly learning collaborative sessions. CONCLUSION: Training PCPs to deliver autism evaluations for young children as part of tiered community-based models of care is a promising solution to address access and waitlist challenges. ADAPT is an intensive, standardized PCP training model that results in achievement of independent competency and sustained engagement in autism evaluation. Effectiveness-implementation studies are needed to ensure scalability and sustainability of training models.

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17. Neul JL, Benke TA, Marsh ED, Suter B, Fu C, Ryther RC, Skinner SA, Lieberman DN, Feyma T, Beisang A, Heydemann P, Peters SU, Ananth A, Percy AK. Clinical Features and Disease Progression in Older Individuals with Rett Syndrome. Genes (Basel);2024 (Aug 22);15(8)

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.

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18. Nowell S, Steinbrenner JR, Wallisch A, Salley B, McGovern J, McGauley S, Watson LR, Irvin D, Buzhardt J, Boyd B. Adapting the Early Communication Indicator as a Social Communication Outcome Measure for Young Autistic Children: A Pilot Study. Am J Speech Lang Pathol;2024 (Aug 22):1-8.

PURPOSE: We sought to conduct a pilot investigation of the reliability and administration fidelity of a new play-based measure of social communication for infants and toddlers with an autism diagnosis. METHOD: Our team adapted an existing measure, the Early Communication Indicator (ECI), for use with young autistic children in clinical and research contexts. In this brief report, we detail our adaptation process including administration and scoring of the final adapted measure based on data from a two-phase pilot study with young autistic children (N = 17). RESULTS: This adapted measure, the Early Communication Indicator-Autism (ECI-A), captured a range of scores for the ECI, Initiation of Joint Attention, and Directed Communication in pilot testing. Interrater reliability was moderate to strong across the scored behaviors. Finally, parents were able to administer the ECI-A with high fidelity with support from the research staff. CONCLUSIONS: This two-phase pilot study demonstrated promise for the ECI-A as a brief measure of social communication that can be administered by parents and reliably scored by trained staff with limited background in autism assessments. Validation of the ECI-A is presently underway. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26042077.

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19. Qi K, Liu Y, Wang Z, Xiong X, Cai K, Xu Y, Shi Y, Sun Z, Dong X, Chen A. Recreational ball games are effective in improving social communication impairments among preschoolers diagnosed with autism spectrum disorder: a multi-arm controlled study. BMC Sports Sci Med Rehabil;2024 (Aug 22);16(1):176.

BACKGROUND: This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD). METHODS: A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS: The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p < 0.05). Despite enhancing the overall scores on the SRS-2, these interventions displayed varying impacts across different sub-dimensions. BCTP primarily exhibited significant enhancements in social awareness and behavior pattern (p < 0.05), whereas MBTP significantly improved social cognition and social communication (p < 0.05). Both interventions showed slight improvements in social motivation. CONCLUSIONS: The utilization of recreational ball games has showed to be effective in decreasing the impairment levels of children with ASD, while the control group experienced a worsening of outcomes. This suggests that irrespective of the specific ball game strategy employed, both can be employed on a weekly basis to complement standard behavioral rehabilitation and enhance the ability to improve the quality of life for children diagnosed with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973;August 5, 2019).

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20. Sandhu A, Rawat K, Gautam V, Kumar A, Sharma A, Bhatia A, Grover S, Saini L, Saha L. Neuroprotective effect of PPAR gamma agonist in rat model of autism spectrum disorder: Role of Wnt/β-catenin pathway. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Aug 22);135:111126.

BACKGROUND: The clinical manifestation of autism spectrum disorder (ASD) is linked to the disruption of fundamental neurodevelopmental pathways. Emerging evidences claim to have an upregulation of canonical Wnt/β-catenin pathway while downregulation of PPARγ pathway in ASD. This study aims to investigate the therapeutic potential of pioglitazone, a PPARγ agonist, in rat model of ASD. The study further explores the possible role of PPARγ and Wnt/β-catenin pathway and their interaction in ASD by using their modulators. MATERIAL AND METHODS: Pregnant female Wistar rats received 600 mg/kg of valproic acid (VPA) to induce autistic symptoms in pups. Pioglitazone (10 mg/kg) was used to evaluate neurobehaviors, relative mRNA expression of inflammatory (IL-1β, IL-6, IL-10, TNF-α), apoptotic markers (Bcl-2, Bax, & Caspase-3) and histopathology (H&E, Nissl stain, Immunohistochemistry). Effect of pioglitazone was evaluated on Wnt pathway and 4 μg/kg dose of 6-BIO (Wnt modulator) was used to study the PPARγ pathway. RESULTS: ASD model was established in pups as indicated by core autistic symptoms, increased neuroinflammation, apoptosis and histopathological neurodegeneration in cerebellum, hippocampus and amygdala. Pioglitazone significantly attenuated these alterations in VPA-exposed rats. The expression study results indicated an increase in key transcription factor, β-catenin in VPA-rats suggesting an upregulation of canonical Wnt pathway in them. Pioglitazone significantly downregulated the Wnt signaling by suppressing the expression of Wnt signaling-associated proteins. The inhibiting effect of Wnt pathway on PPARγ activity was indicated by downregulation of PPARγ-associated protein in VPA-exposed rats and those administered with 6-BIO. CONCLUSION: In the present study, upregulation of canonical Wnt/β-catenin pathway was demonstrated in ASD rat model. Pioglitazone administration significantly ameliorated these symptoms potentially through its neuroprotective effect and its ability to downregulate the Wnt/β-catenin pathway. The antagonism between the PPARγ and Wnt pathway offers a promising therapeutic approach for addressing ASD.

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21. Shangguan S, Zhang X, Ge Y, Han Y, Xiao L, Zhang Y, Xie H, Chen X, Wang X. Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2. Mol Genet Genomics;2024 (Aug 22);299(1):81.

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.

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22. Shyu HJ, Ryan Chen YW, Yih Ng D, Bundy A, Tseng MH, Cordier R. Does the PedsQL reflect the real-time quality of life in autistic adolescents? A comparison with the experience sampling methodology. Disabil Health J;2024 (Aug 22):101690.

BACKGROUND: The PedsQL is widely used to retrospectively evaluate quality of life (QoL) in autistic adolescents. However, concerns have arisen regarding its ability to reflect real-time QoL, considering their challenges in recollecting past experiences. OBJECTIVE: We examined the overall and social QoLs of autistic adolescents compared to neurotypical peers using the PedsQL and the experience sampling method (ESM), an ecological momentary assessment of QoL in real-time. Additionally, we explored the relationship between these measures in each group. METHODS: A total of 175 participants, including 117 autistic and 58 neurotypical adolescents aged 10-16, completed the PedsQL and an ESM protocol with a mobile device to record their real-time experiences seven times a day for seven days. We performed multiple linear regression and multilevel analyses to compare QoLs between groups and the association between the two measures. RESULTS: Autistic adolescents scored significantly lower than neurotypical peers on PedsQL overall and social QoL but not on the real-time experiences collected with ESM. Among neurotypical adolescents, we found significant associations between the Social Functioning score of the PedsQL and various aspects of real-time social experiences recorded with ESM. For autistic adolescents, only the real-time experience of ‘loneliness’ during social engagement was associated with Social Functioning on the PedsQL. CONCLUSIONS: The retrospective PedsQL does not entirely capture the real-time QoL via ESM. However, relying solely on ESM may overlook situations where participants opt out or could not complete surveys. Thus, using both retrospective and real-time assessments to examine QoL among autistic adolescents is recommended.

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23. Souza AJ, Freitas Í S, Sharmin D, Cook JM, Guimarães FS, Gomes FV. An alpha 5-GABA(A) receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero. Autism Res;2024 (Aug);17(8):1534-1544.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABA(A) receptors (α5-GABA(A)Rs) SH-053-2’F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2’F-R-CH3 could attenuate these changes. SH-053-2’F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2’F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2’F-R-CH3. Despite sex differences, our findings indicate that α5-GABA(A)Rs positive allosteric modulators may effectively attenuate some core ASD symptoms.

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24. Sutherland R, Turnbull A, Toms A, Perry C, Watts A. Australian SLPs’ knowledge and actions regarding the early signs of autism: When does caution become gatekeeping?. Int J Speech Lang Pathol;2024 (Aug 21):1-13.

PURPOSE: Speech-language pathologists (SLPs) are often the first point of contact for families of children with autism. Despite this, little is known about SLPs’ understanding of autism and its early indicators. This study sought to investigate what Australian SLPs know about autism, the early indicators, and the actions they take when they identify these characteristics. METHOD: A 34 question cross-sectional online survey was distributed through professional networks, social media channels, and industry contacts to Australian SLPs. Quantitative and qualitative data were analysed. RESULT: The 70 participants worked in various contexts around the country. The majority of participants demonstrated sound knowledge of the main characteristics of autism, and some early indicators. Quantitative analysis identified a significant correlation between participant age and confidence talking to parents about possible autism. Overarching themes were identified: (a) caution may delay or prevent SLPs from taking action, (b) some factors may influence SLPs’ action, and (c) SLPs take action. CONCLUSION: Australian SLPs working with children have the knowledge and understanding of the main characteristics of autism and some early indicators. However, they demonstrate a cautious approach around the subject of autism, and this caution may cause delays for children requiring diagnostic services.

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25. Taylor JA, Smith ZZ, Anderson ME, Holbrook EM, Elkinbard IS, Reuter JD, Lowry CA, Barth DS. Prenatal broad-spectrum cannabidiol administration prevents an autism-like phenotype in male offspring from a maternal stress/terbutaline rat model. Brain Behav Immun Health;2024 (Oct);40:100828.

Recently, the diagnosis of autism spectrum disorder (ASD) has increased from 1 in 150 to every 1 in 36 children in the United States, warranting a need for novel prevention and therapeutic strategies. Broad-spectrum cannabidiol oil, free from delta-9-tetrahydrocannabinol, the psychoactive component of cannabis, may be one such therapeutic. It has a high safety profile and is frequently used as a complementary and integrative intervention by persons experiencing symptoms of anxiety, stress, and inflammation. Using a neurodevelopmental rat model of ASD (based on neuroinflammation induced by stress and terbutaline exposure during pre- and postnatal development), we sought to prevent the development of ASD-like behaviors in male offspring by administering broad-spectrum cannabidiol oil to dams throughout pregnancy (10 mg/kg, i.p., daily, embryonic days 3-16). To assess an ASD-like phenotype in the offspring, we used three behavioral measures relevant to three core ASD symptoms: 1) social communication (time spent vocalizing when alone); 2) repetitive behavior (marbles buried during a marble burying test); and 3) social interaction (time spent interacting with a novel conspecific during the three-chamber social interaction test). Broad-spectrum cannabidiol oil given during pregnancy decreased scores for all three ASD-related behavioral responses, resulting in an overall significant prevention of the ASD-like phenotype. These findings highlight the potential of broad-spectrum cannabidiol oil as a complementary and integrative approach for prevention of stressor-induced sequelae relevant to development of an ASD-like phenotype.

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26. Ünsel-Bolat G, Bolat H. Phenotypes of autism spectrum disorder and schizoaffective disorder associated with SETD1B gene but without intellectual disability and seizures. Int J Dev Neurosci;2024 (Aug 21)

The SETD1B gene, located on chromosome 12q24, is one of the chromatin-modifying genes involved in epigenetic regulation of gene transcription. The phenotype of pathogenic variants in the SETD1B gene includes intellectual disability, seizures, and language delay (IDDSELD, OMIM 619000). In this study, we present a family consisting of consanguineous parents who died of cancer and their offspring. This family includes two cases diagnosed with autism spectrum disorder (ASD); six cases diagnosed with schizophrenia, bipolar disorder, or schizoaffective disorder; there cases diagnosed with cancer; and five cases who died of unknown causes in early childhood. Three affected members of this family agreed to genetic testing. We used whole exome sequencing. We report a novel in-frame deletion variant of the SETD1B gene in a family with cases diagnosed with schizoaffective disorder and ASD without seizures and intellectual disability. It was found that the phenotypic features were inherited for at least three generations in the family we presented, and it was shown that the pathogenic variant of the SETD1B gene was transmitted from the affected parent to his affected children. In addition, the father was diagnosed with both schizoaffective disorder and leukemia. We proposed an association between rare variants of SETD1B and phenotypes of ASD and schizoaffective disorder without seizures and intellectual disability. The SETD1B gene is included in both the ASD genetic database of SFARI (https://gene.sfari.org/) and the cancer database of COSMIC (https://cancer.sanger.ac.uk/cosmic). However, there are very few reports of SETD1B gene variants as clinical entities. To our knowledge, the SETD1B gene variant has not been previously reported in an individual diagnosed with both a neuropsychiatric disorder and cancer.

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27. Xiong W, Li X, Huang X, Xu J, Qu Z, Su Y, Li Y, Han Y, Cui T, Zhang X. Impaired motor and social skill development in infancy predict high autistic traits in toddlerhood. Neuroscience;2024 (Aug 20);558:114-121.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder. Early diagnosis in the critical period is important for ASD children. Recent studies of neurodevelopmental behavioral features and joint attention in high-risk infants showed there are some special cues which can distinguish ASD from typical development infant. But the findings of high-risk population may not be applicable to the general population. It is necessary to « analogically » study the potential warning traits of ASD in infancy in the general population. We did a nested case-control study from June 2019 to November 2022 in Tianjin, China, including 76 general infants whom completed the neurodevelopmental evaluation, the Checklist for Autism in Toddlers-23 (CHAT-23) screening, and eye tracking task. Social behavior quotient in infancy was negatively correlated to CHAT-23 total scores in toddlerhood. Social behavior quotient in infancy was positively correlated to initiating joint attention in toddlerhood. Regression model showed that high fine motor scale and social behaviour scale quotient in infancy were associated with an decreased risk of the total score of CHAT-23 ≥ 2 in toddlerhood. The Receiver operating characteristic curve showed the social behaviour in infancy alone and the combination of fine motor and social behaviour in infancy contributed to auxiliary diagnosis of higher level of autistic traits in toddlerhood. These findings suggest that Impaired development of fine motor and social behavior in infancy are potential warning features of high autistic traits in general population.

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28. Yang D, Svoboda AM, George TG, Mansfield PK, Wheelock MD, Schroeder ML, Rafferty SM, Sherafati A, Tripathy K, Burns-Yocum T, Forsen E, Pruett JR, Marrus NM, Culver JP, Constantino JN, Eggebrecht AT. Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography. Mol Autism;2024 (Aug 22);15(1):35.

BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits. METHODS: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models. RESULTS: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits. LIMITATIONS: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism. CONCLUSIONS: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits.

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29. Zaharia A, Kojovic N, Rojanawisut T, Sander D, Schaer M, Samson AC. Examining the Link Between Social Affect and Visual Exploration of Cute Stimuli in Autistic Children. J Autism Dev Disord;2024 (Aug 22)

Baby schema refers to physical features perceived as cute, known to trigger attention, induce positive emotions, and prompt social interactions. Given the reduced visual attention to social stimuli observed in individuals on the autism spectrum, the current study examines whether the sensitivity to baby schema is also affected. We expected that the looking time towards cute-featured stimuli would vary with symptom severity levels and would be associated with social affect. Ninety-four children (31 typically developing; 63 diagnosed with autism spectrum disorder – ASD) aged 20-83 months (M = 49.63, SD = 13.59) completed an eye-tracking visual exploration task. Autistic participants were separated into two groups based on symptom severity: children with high autism severity symptoms (HS ASD; N = 23) and low-moderate autism symptoms (LMS ASD; N = 40). Animals and neutral objects were simultaneously presented on the screen along with either human babies (condition 1) or adults (condition 2). The results indicated that visual attention oriented to cute-featured stimuli varied with autism symptom severity: only LMS and TD groups spend more time looking at cute-featured stimuli (babies; animals) than neutral objects. Moreover, children with higher severity in the social affect domain spent less time on the stimuli depicting cute than non-cute stimuli. These findings suggest that autism symptom severity and social skills are linked to variations in visual attention to cute stimuli. Implications of baby schema sensitivity are discussed in relation to the development of social competencies and play, responsiveness to robot-based interventions, as well as appraised relevance in autistic children.

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30. Zahedi E, Sadr SS, Sanaeierad A, Hosseini M, Roghani M. Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation. Neuroscience;2024 (Aug 20);558:92-104.

This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.

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31. Zandam H, Moura I, Akobirshoev I, Mitra M. Non-COVID Respiratory Infections Emergency Room Visits Among Autistic in the United States. Am J Prev Med;2024 (Aug 22)

INTRODUCTION: This is a retrospective study to examine the risk of non-COVID-19 respiratory infection (RI) related emergency department (ED) visits and hospitalizations among autistic adults compared to non-autistic adults using the 2018 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample (HCUP-NEDS). METHODS: The data were analyzed in 2022 using the ICD-10-CM codes to extract about 46,996 autistic case records that were matched by age and sex with non-autistic records (140,997) in a 1:3 case-control ratio. Respiratory infections were also identified using the ICD-10-CM codes and classified by type. Logistic regression models were conducted for the likelihood of presenting with RI infections to the ED and subsequent hospitalization. All models were adjusted for covariates. RESULTS: Autistics were more likely to present with any type of respiratory infection at the emergency department (AOR = 1.83: CI= 1.69-2.42), lower respiratory infections (AOR=1.37: CI=1.09-1.50), and pneumonia (AOR=2.42: CI=1.98-2.47) compared to non-autistics. They are also more likely to be hospitalized from RIs during ED visits (AOR=3.87: CI=3.21-4.30), including upper and lower RIs, pneumonia, and bronchitis. CONCLUSIONS: Autistic individuals were more likely to experience emergency department visits and hospitalizations due to respiratory infections compared to non-autistic individuals. Amid growing evidence of the disproportionate impact of COVID-19 on the autistic population, our findings highlight a broader, pre-existing burden of respiratory infections among autistic adults in the US that extends beyond the recent pandemic.

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32. Zhou X, Siddiqui H, Rutherford MD. Face perception and social cognitive development in early autism: A prospective longitudinal study from 3 months to 7 years of age. Child Dev;2024 (Aug 22)

Autism spectrum condition (ASC) is characterized by atypical attention to eyes and faces, but the onset and impact of these atypicalities remain unclear. This prospective longitudinal study examined face perception in infants who develop ASC (N = 22, female = 5, 100% White) compared with typically developing infants (N = 131, female = 65, 55.6% White), tracking social-cognitive and ASC development through age seven. Reduced interest in direct gaze and eyes during infancy correlated with atypical development of adaptive behavior at age four and theory of mind at age seven. Principal component analyses revealed less integrated processing of facial features and eye-gaze information in ASC infants, potentially impacting their childhood social functioning. These findings highlight the intertwined nature of social-cognitive development and ASC.

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