1. Caplan B, Chlebowski C, Lind T, Rangel E, Brookman-Frazee L. Therapist-Reported Adaptations to an Autism Intervention: Family-Level Predictors and Associations with Fidelity. J Autism Dev Disord. 2024.

The purpose of this study was to: (1) confirm the factor structure of a therapist-report measure of adaptations to an autism evidence-based intervention (EBI), (2) identify predictors of adaptation types, and (3) examine associations of adaptation types with observed therapist fidelity. Participants included a subset of therapists (N = 70; 31.4% Hispanic), autistic children (N = 79; ages 5-13 years; 57.0% Hispanic), and their caregivers (N = 77; 54.5% Hispanic), who participated in the training condition of a community effectiveness trial of An Individualized Mental Health Intervention for Autism (AIM HI). Families reported demographics and completed assessments of child functioning and caregiver strain at baseline. Therapists submitted video recordings of psychotherapy sessions during EBI training, which were later coded for fidelity by independent raters. Therapists completed the Adaptations to Evidence-Based Practices Scale at the end of the 6-month training period. Multi-level confirmatory factor analysis yielded two adaptation types consistent with prior research: Augmenting and Reducing/Reordering adaptations. In multi-level models, higher Augmenting adaptations were associated with lower child cognitive functioning (B= -0.01, p < .05), higher child autism characteristics (B = 0.01, p < .05), and Non-Hispanic White caregiver ethnicity (B = - 0.17, p < .01). Higher Reducing/Reordering adaptations were associated with Non-Hispanic White caregiver race/ethnicity only (B = - 0.33, p < .01). There were no significant associations between therapist-reported adaptations and observed fidelity. This study further supports Augmenting and Reducing/Reordering as distinct subtypes of adaptations with unique predictors. Therapists likely adapt AIM HI to tailor the EBI to individual client needs and do so in ways that do not appear to interfere with fidelity. Trial Registration ClinicalTrials.gov identifier NCT02416323.

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2. Cheong PL, Wu YT, Lin CW, Huang FY, Pan YL, Kuo HI, Sun JL, Huang CY. Feasibility of a Home-Based Developmental Behavioral Intervention for Children With Autism Spectrum Disorder in Underserved Taiwanese Families. Pediatr Phys Ther. 2024.

PURPOSE: This study aims to investigate the feasibility of the home-based parent- mediated intervention Naturalistic developmental behavioral intervention (HB-NDBI) in underserved Taiwanese families of children with Autism spectrum disorder (ASD) and explore its effects on children’s developmental skills and parents’ parenting stress. METHOD: 24 underserved Taiwanese families of children with ASD (mean age = 46.5 months) received 12-week HB-NDBI programs. Social Responsiveness Scale, Second Edition (SRS-2), Mullen Scales of Early Learning (MSEL), Child Behavior Checklist (CBCL/1.5-5), and Parenting Stress Index (PSI) were administered before and after the HB-NDBI programs. RESULTS: Following the HB-NDBI programs, significant improvements in social cognition, social communication subscales, receptive language subscale, internalizing, externalizing, and total behavioral problems scales of children, and release of parenting stress were observed. CONCLUSION: This study demonstrated the feasibility of home-based parent-mediated intervention for underserved families in Taiwan. These promising results might facilitate the development of such interventions for underserved families.

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3. Cowen MH, Haskell D, Zoga K, Reddy KC, Chalasani SH, Hart MP. Conserved autism-associated genes tune social feeding behavior in C. elegans. Nat Commun. 2024; 15(1): 9301.

Animal foraging is an essential and evolutionarily conserved behavior that occurs in social and solitary contexts, but the underlying molecular pathways are not well defined. We discover that conserved autism-associated genes (NRXN1(nrx-1), NLGN3(nlg-1), GRIA1,2,3(glr-1), GRIA2(glr-2), and GLRA2,GABRA3(avr-15)) regulate aggregate feeding in C. elegans, a simple social behavior. NRX-1 functions in chemosensory neurons (ADL and ASH) independently of its postsynaptic partner NLG-1 to regulate social feeding. Glutamate from these neurons is also crucial for aggregate feeding, acting independently of NRX-1 and NLG-1. Compared to solitary counterparts, social animals show faster presynaptic release and more presynaptic release sites in ASH neurons, with only the latter requiring nrx-1. Disruption of these distinct signaling components additively converts behavior from social to solitary. Collectively, we find that aggregate feeding is tuned by conserved autism-associated genes through complementary synaptic mechanisms, revealing molecular principles driving social feeding.

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4. Ding Y, Zhang H, Qiu T. Deep learning approach to predict autism spectrum disorder: a systematic review and meta-analysis. BMC Psychiatry. 2024; 24(1): 739.

BACKGROUND: The use of the deep learning (DL) approach has been suggested or applied to identify childhood autism spectrum disorder (ASD). The capacity to predict ASD, however, differs across investigations. Our study’s objective was to conduct a meta-analysis to determine the DL for ASD in children’s classification accuracy. METHODS: Eligibility criteria were designed according to the purpose of the meta-analysis; PubMed, EMBASE, Cochrane Library, and Web of Science Database were searched for articles published up to April 16, 2023, on the accuracy of DL methods for ASD classification. Using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) to assess the quality of the included studies. Sensitivity, specificity, areas under the curve (AUC), summary receiver operating characteristic (SROC), and corresponding 95% confidence intervals (CIs) were compiled by using the bivariate random-effects models. RESULTS: A total of 11 predictive trials based on DL models were included, involving 9495 ASD patients from 6 different databases. According to bivariate random-effects models’ results, the overall sensitivity, specificity, and AUC of the DL technique for ASD were, 0.95 (95% CI = 0.88-0.98), 0.93 (95% CI = 0.85-0.97), and 0.98 (95%CI: 0.97-0.99), respectively. Subgroup analysis results found that different datasets did not cause heterogeneity (meta-regression P = 0.55). The Kaggle dataset’s sensitivity and specificity were 0.94 (95%CI: 0.82-1.00) and 0.91 (95%CI: 0.76-1.00), and with 0.97 (95%CI: 0.92-1.00) and 0.97 (95%CI: 0.92-1.00) for ABIDE dataset. CONCLUSIONS: DL techniques has satisfactory sensitivity, specificity, and AUC in ASD classification. However, the major heterogeneity of the included studies limited the effectiveness of this meta-analysis. Further trials need to be performed to demonstrate the clinical practicability of DL diagnosis.

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5. Fletcher L, Rabagliati H, Culbertson J. Autistic Traits, Communicative Efficiency, and Social Biases Shape Language Learning in Autistic and Allistic Learners. Cogn Sci. 2024; 48(11): e70007.

There is ample evidence that individual-level cognitive mechanisms active during language learning and use can contribute to the evolution of language. For example, experimental work suggests that learners will reduce case marking in a language where grammatical roles are reliably indicated by fixed word order, a correlation found robustly in the languages of the world. However, such research often assumes homogeneity among language learners and users, or at least does not dig into individual differences in behavior. Yet, it is increasingly clear that language users vary in a large number of ways: in culture, in demographics, and-critically for present purposes-in terms of cognitive diversity. Here, we explore how neurodiversity impacts behavior in an experimental task similar to the one summarized above, and how this behavior interacts with social pressures. We find both similarities and differences between autistic and nonautistic English-speaking individuals, suggesting that neurodiversity can impact language change in the lab. This, in turn, highlights the potential for future research on the role of neurodivergent populations in language evolution more generally.

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6. Gosselin Hills J, Bowen SK. Kendra’s journey: an intrinsic case study of a deaf autistic child. J Deaf Stud Deaf Educ. 2024.

This study used an intrinsic case study to investigate how interventions from applied behavior analysis impacted language development, academic progress, and the reduction of severe challenging behaviors for an 8-year-old child who is Deaf and autistic. 3 main themes were identified: language acquisition, behavioral change strategies, and academic performance. Additionally, 2 common threads wove in and out of each and connected all 3 themes: language access and qualified providers, including Deaf professionals. This study expands the literature about using behavioral strategies with children who are Deaf and autistic and discusses implications for clinical and educational practice.

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7. Holyfield C, Zimmerman TO, MacNeil S, Caldwell NS, Patel P, Griffen B, Lorah E, Dragut E, Vucetic S. Preliminary Investigation of Context-Aware AAC with Automated Just-in-Time Cloze Phrase Response Options for Social Participation from Children on the Autism Spectrum. Folia Phoniatr Logop. 2024: 1-21.

INTRODUCTION: Social participation for emerging symbolic communicators on the autism spectrum is often restricted. This is due in part to the time and effort required for both children and partners to use traditional augmentative and alternative communication (AAC) technologies during fast-paced social routines. Innovations in artificial intelligence provide the potential for context-aware AAC technology that can provide just-in-time (JIT) communication options based on linguistic input from partners to minimize the time and effort needed to use AAC technologies for social participation. METHODS: This preliminary study used an alternating treatment design to compare the effects of a context-aware AAC prototype with automated cloze phrase response options to traditional AAC for supporting three young children who were emerging symbolic communicators on the autism spectrum in participating within a social routine. RESULTS: Visual analysis and effect size estimates suggest the context-aware AAC condition resulted in increases in linguistic participation, vocal approximations, and visual attention for all three children. CONCLUSION: While this study was only an initial exploration and results are preliminary, context-aware AAC technologies have the potential to enhance participation and communication outcomes for young emerging symbolic communicators on the autism spectrum and more research is needed.

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8. Ihekweazu FD, Motil KJ. Gastrointestinal manifestations of Rett syndrome: An updated analysis using the Gastrointestinal Health Questionnaire. J Pediatr Gastroenterol Nutr. 2024.

OBJECTIVE: We conducted a nationwide survey using a validated Gastrointestinal Health Questionnaire (GHQ) for Rett syndrome (RTT) to provide an updated and accurate baseline assessment of the prevalence of common gastrointestinal (GI) issues in RTT, based on parental reporting. METHODS: Parents and caregivers of females with RTT or normally developing, unaffected, age-matched controls completed the GHQ survey. The prevalence of GI symptoms and personality and mood symptoms due to stomach or intestinal problems, as well as GI medication usage and surgical interventions, were assessed in females with RTT and unaffected controls. The relation between GI symptoms and medication usage, surgical status, age, and genetic mutation were analyzed. RESULTS: Parents of 118 females with RTT and 27 unaffected females completed the GHQ. GI symptoms were common in females with RTT, including constipation (81%), gas and bloating (70%), issues with eating, chewing and swallowing (73%), and irritability because of stomach or intestinal problems (53%). Females with RTT commonly used proton pump inhibitors (52%) and laxatives (64%). Medication usage was associated with significantly higher GHQ symptom scores. Parents of individuals with RTT reported a significantly higher prevalence of GI symptoms affecting their daughters in all symptom categories compared with unaffected females. CONCLUSIONS: GI problems are common in RTT and pose a significant medical burden to caregivers. The GHQ is a useful tool to assess GI issues in individuals with RTT. Improved recognition of these issues may allow for improved treatment and enhanced quality of life for girls and women affected by RTT.

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9. Iniutina O. Key principles of the KiDD (kids’ development diagnosis and determining the risk of autism for children from 1.5 to 6 years) methodology development and comparison of results with other methods. Glob Ment Health (Camb). 2024; 11: e88.

The author outlines the basic principles of creating the KiDD methodology (Kids’ Development Diagnosis and Determining the Risk of Autism) for children aged 1.5 to 6 years old in the form of a mobile application. Users of the KiDD (parents or specialists) instantly receive information about the general development of the child in comparison with the age at which certain skills emerge. This includes information about the developmental age in months for each developmental area (speech and communication, socialization and behavior, cognitive skills, physical development and self-care), the developmental age for each specific skill of the child (up to 100 skills in each age category from 1.5 to 6 years) and the likelihood of autism. Additionally, users receive an automatically generated Individual Development Plan, consisting of skills that follow those that the child already has. The author provides statistical data comparing the results obtained through the KiDD with the results of widely accepted tests for assessing a child’s developmental level and the likelihood of autism. The article presents comparative data of the results of 199 participants using the KiDD along with their respective diagnoses and results obtained through testing provided by psychologists and remote assessment provided by parents.

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10. Khan H, Rihal V, Kaur A, Singh TG. Proposed Hypothesis of TWEAK/Fn14 Receptor Modulation in Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2024.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a complex, multiple etiology that is marked by impaired social interaction, communication, and repetitive behaviour. There is presently no pharmaceutical treatment for the core symptoms of ASD, even though the prevalence of ASD is increasing worldwide. Treatment of autism spectrum disorder involves the interaction of numerous signalling pathways, such as the Wnt/beta-catenin pathway, probiotics and kynurenine pathway, PPAR pathway, PI3K-AKT-mTOR pathway, Hedgehog signaling pathway, etc. The scientific literature has revealed TWEAK/Fn14 to not be explored in the autism spectrum disorder. In vitro and in vivo, TWEAK can control a wide range of cellular responses. Recent research has revealed that TWEAK and Fn14 are expressed in the Central Nervous System (CNS) and upregulated in perivascular endothelial cells, astrocytes, neurons, and microglia in response to various stimuli, including cerebral ischemia. This upregulation is followed by cell death and an increase in Blood-brain Barrier (BBB) permeability. The study has revealed that Aurintricarboxylic Acid (ATA) acts as an agent that suppresses TWEAK/Fn14 signaling. Similarly, from the discussion, it has been emphasized that the proposed molecular TWEAK/Fn14 signalling pathway can be considered as a therapeutic approach in the management of autism spectrum disorder.

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11. Larnyo E, Nutakor JA, Addai-Dansoh S, Nkrumah ENK. Sentiment analysis of post-COVID-19 health information needs of autism spectrum disorder community: insights from social media discussions. Front Psychiatry. 2024; 15: 1441349.

OBJECTIVE: This study explores the health information needs of individuals with autism spectrum disorder (ASD) and their caregivers in the post-COVID-19 era by analyzing discussions from Reddit, a popular social media platform. METHODS: Utilizing a mixed-method approach that integrates qualitative content analysis with quantitative sentiment analysis, we analyzed user-generated content from the « r/autism » subreddit to identify recurring themes and sentiments. RESULTS: The qualitative analysis uncovered key themes, including symptoms, diagnostic challenges, caregiver experiences, treatment options, and stigma, reflecting the diverse concerns within the ASD community. The quantitative sentiment analysis revealed a predominance of positive sentiment across discussions, although significant instances of neutral and negative sentiments were also present, indicating varied experiences and perspectives among community members. Among the machine learning models used for sentiment classification, the Bi-directional Long Short-Term Memory (Bi-LSTM) model achieved the highest performance, demonstrating a validation accuracy of 95.74%. CONCLUSIONS: The findings highlight the need for improved digital platforms and community resources to address the specific health information needs of the ASD community, particularly in enhancing access to reliable information and fostering supportive environments. These insights can guide future interventions and policies aimed at improving the well-being of autistic persons and their caregivers.

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12. Lee J, Lim J, Kang S, Kim S, Jung SY, Kim S, Hong SB, Park YR. Mobile App-Assisted Parent Training Intervention for Behavioral Problems in Children With Autism Spectrum Disorder: Pilot Randomized Controlled Trial. JMIR Hum Factors. 2024; 11: e52295.

BACKGROUND: In children with autism spectrum disorder (ASD), problem behaviors play a dysfunctional role, causing as much difficulty with daily living and adjustment as the core symptoms. If such behaviors are not effectively addressed, they can result in physical, economic, and psychological issues not only for the individual but also for family members. OBJECTIVE: We aimed to develop and evaluate the feasibility of a mobile app-assisted parent training program for reducing problem behaviors in children with ASD. METHODS: This open-label, single-center, randomized controlled trial was conducted among parents of children with ASD aged 36-84 months. Participants were recruited from the Department of Psychiatry at Seoul National University Hospital. Participants were randomly assigned (1:1) by a blinded researcher. Randomization was performed using a stratified block randomization (with a block size of 4). Parents in the intervention group completed the mobile app-assisted parent training program at home over a 12-week period. They continued to receive their usual nondrug treatment in addition to the mobile app-assisted parent training program. The control group continued to receive their usual nonpharmaceutical treatment for 12 weeks without receiving the parent training program intervention. The primary outcome measure was the median change in the Korean Child Behavior Checklist (K-CBCL) scores from before to after the intervention. Lower scores on the K-CBCL indicated a decrease in overall problem behavior. RESULTS: Between November 9, 2022, and December 8, 2022, 64 participants were enrolled. Overall, 42 children (intervention group median age: 49, IQR 41-52.5 months; control group median age: 49, IQR 42-58 months) of the participants joined the program. The intervention group included 20 (48%) participants and the control group included 22 (52%) participants. In the intervention group, the K-CBCL total scores showed a decrease after the intervention, with a median difference of -0.5 (95% CI -4.5 to 3). Pervasive developmental disorder scores also showed a decrease, with a median difference of -2.1 (95% CI -8.5 to 2.5). However, there was no significant difference in Clinical Global Impression-Severity of Illness scores after the intervention for both the control and intervention groups. Scores on the Korean version of the Social Communication Questionnaire showed a further decrease after the intervention in the intervention group (median difference -2, 95% CI -4 to 1). Caregivers’ stress evaluated using the Korean Parenting Stress Index Fourth Edition-Short Form did not show any significant differences between the control and intervention groups. There were no adverse events related to study participation. CONCLUSIONS: The findings demonstrated the feasibility of using mobile devices for evidence-based parent training to reduce problem behaviors in children with ASD. Mobile devices’ accessibility and flexibility may provide a viable alternative for offering early intervention for problem behaviors in children with ASD. TRIAL REGISTRATION: CRIS KCT0007841; https://cris.nih.go.kr/cris/search/detailSearch.do?&seq=23112.

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13. Li SN, Chien WT, Lam SKK, Chong YY, Gloster AT. Psychometric Properties of the Chinese Version of the Psy-Flex Among Parents of Children with Autism Spectrum Disorder. J Autism Dev Disord. 2024.

This research aimed to translate the original English version of the Psy-Flex, a scale of psychological flexibility, into Chinese and to test its psychometric properties among parents of children with autism spectrum disorder (ASD). Two phases were conducted: (1) translation from English to Chinese (Psy-Flex-C), followed by a semantic equivalence evaluation between two versions, a pre-test, and an evaluation of the Psy-Flex-C in terms of face validity with 20 parents of autistic children, and content validity of the Psy-Flex-C with eight experts. (2) A cross-sectional study with 248 parents of autistic children was conducted for validation, and a subgroup of 50 participants was randomly selected to assess the test-retest reliability at a 2-week interval. The Psy-Flex-C showed satisfactory semantic equivalence with the original version and demonstrated adequate internal consistency (Cronbach’s α = 0.84) and test-retest stability (weighted kappa statistic = 0.88). Concurrent validity was supported by a moderate correlation between the Psy-Flex-C and the Comprehensive Assessment of Acceptance and Commitment Therapy Processes (Pearson’s r = 0.54, p < 0.01). The Psy-Flex-C showed a significant mean score difference between parents with high and low parenting stress (t = 5.43, p < 0.001). Similar to the original scale, confirmatory factor analysis showed the best fitting one-factor structure of the Psy-Flex-C (X(2)/df = 1.62, p = 0.13, RMSEA = 0.05, GFI = 0.99, CFI = 0.99, TLI = 0.98, SRMR = 0.023). The Psy-Flex-C can be a reliable and valid instrument to self-report psychological flexibility in parents of children with ASD. Future research is recommended to test the Psy-Flex-C using diverse samples from different cultures and contexts to enhance its generalizability.

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14. Lu L, Sarkar AK, Dao L, Liu Y, Ma C, Thwin PH, Chang X, Yoshida G, Li A, Wang C, Westerkamp C, Schmitt L, Chelsey M, Stephanie M, Zhao Y, Liu Y, Wang X, Zhu LQ, Liu D, Tchieu J, Miyakoshi M, Zhu H, Gross C, Pedapati E, Salomonis N, Erickson C, Guo Z. An iPSC model of fragile X syndrome reflects clinical phenotypes and reveals m (6) A-mediated epi-transcriptomic dysregulation underlying synaptic dysfunction. bioRxiv. 2024.

Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from FMR1 gene silencing and loss of the FMRP protein. N6-methyladenosine (m (6) A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m (6) A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m (6) A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m (6) A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m (6) A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m (6) A modifications in FXS, suggesting a promising avenue for m (6) A-targeted therapies.

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15. Medina E, Rempe MJ, Muheim C, Schoch H, Singletary K, Ford K, Peixoto L. Sex differences in sleep deficits in mice with an autism-linked Shank3 mutation. Biol Sex Differ. 2024; 15(1): 85.

BACKGROUND: Insomnia is more prevalent in individuals with Autism Spectrum Disorder (ASD), can worsen core-symptoms and reduces quality of life of both individuals and caregivers. Although ASD is four times more prevalent in males than females, less is known about sex specific sleep differences in autistic individuals. Recent ASD studies suggest that sleep problems may be more severe in females, which aligns with the sex bias seen in insomnia for the general population. We have previously shown that male mice with a mutation in the high confidence ASD gene Shank3, Shank3(∆C), recapitulate most aspects of the ASD insomnia phenotype. The objective of the present study was to leverage the Shank3(∆C) model to investigate sex-specific effects in sleep using polysomnography. METHODS: Adult male and female Shank3(∆C) and wildtype (WT) littermates were first recorded for 24 h of baseline recordings. Subsequently, they were sleep deprived (SD) for five hours via gentle handling and allowed 19 h of recovery sleep to characterize the homeostatic response to SD. Vigilance states (rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wake) were assigned by manual inspection using SleepSign. Data processing, statistical analysis and visualization were conducted using MATLAB. RESULTS: Sex and genotype effects were found during baseline sleep and after SD. At baseline, male Shank3(∆C) mice sleep less during the dark period (active phase) while female Shank3(∆C) mice sleep less during the light period (rest phase) and sleep more during the dark period. Both male and female Shank3(∆C) mice show reduced spectral power in NREM sleep. We detect a significant effect of sex and genotype in sleep onset latency and homeostatic sleep pressure (sleepiness). In addition, while male Shank3(∆C) mice fail to increase sleep time following SD as seen in WT, female Shank3(∆C) mice decrease sleep time. CONCLUSIONS: Overall, our study demonstrates sex differences in sleep architecture and homeostatic response to SD in adult Shank3(∆C) mice. Thus, our study demonstrates an interaction between sex and genotype in Shank3(∆C) mice and supports the use of the Shank3(∆C) model to better understand mechanisms contributing to the sex differences in insomnia in ASD in clinical populations. Sleep problems are common in people with Autism Spectrum Disorder (ASD) and can make their condition worse, impacting both their lives and those of their caregivers. Historically ASD has been diagnosed more often in males and much less is known about the female phenotype. However, recent studies suggest that sleep problems may be more severe in autistic females. We previously shown that the ASD mouse model, Shank3(∆C), display an autism like sleep phenotype. Using this model, we examine sex specific deficits in sleep. We investigated canonical measures of sleep during undisturbed conditions (sleep architecture) and after sleep deprivation (sleep homeostasis).Our findings revealed that male Shank3(∆C) mice slept less during their active period while female Shank3(∆C) mice slept less during their rest period and more during their active period. In addition, both male and female Shank3(∆C) mice displayed lower sleep quality. After sleep deprivation, both male and female Shank3(∆C) mice took longer to fall asleep despite accumulation of sleep pressure, however, differences in sleep time after sleep deprivation differed based on sex. In healthy controls, sleep time increases after sleep deprivation. Male Shank3(∆C) mice showed no such increase in sleep time, while female Shank3(∆C) mice slept even less. Our results suggest sex specific differences in two hallmark measures of sleep, architecture and sleep homeostasis in this ASD model. These results highlight the importance of awareness of sex specific differences when studying sleep in ASD as well as eventual treatment or interventions. eng.

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16. Mendoza O, St John L, Tarzi G, Thakur A, Lake JK, Lunsky Y. Predictors of mental well-being among family caregivers of adults with intellectual and developmental disabilities during COVID-19. BJPsych Open. 2024; 10(6): e191.

BACKGROUND: Internationally, stresses related to the COVID-19 pandemic negatively affected the mental health of family caregivers of adults with intellectual and developmental disabilities (IDDs). AIMS: This cross-sectional study investigated demographic, situational and psychological variables associated with mental wellbeing among family caregivers of adults with IDDs during the COVID-19 pandemic. METHOD: Baseline data from 202 family caregivers participating in virtual courses to support caregiver mental well-being were collected from October 2020 to June 2022 via online survey. Mental well-being was assessed using total scores from the Warwick-Edinburgh Mental Wellbeing Scale. Demographic, situational and psychological contributors to mental well-being were identified using hierarchical regression analysis. RESULTS: Variables associated with lower levels of mental well-being were gender (women); age (<60 years old); lack of vaccine availability; loss of programming for their family member; social isolation; and low confidence in their ability to prepare for healthcare, support their family member's mental health, manage burnout and navigate healthcare and social systems. Connection with other families, confidence in managing burnout and building resilience and confidence in working effectively across health and social systems were significant predictors of mental well-being in the final regression model, which predicted 55.6% of variance in mental well-being (P < 0.001). CONCLUSIONS: Family caregivers need ways to foster social connections with other families, and support to properly utilise healthcare and social services during public health emergencies. Helping them attend to their needs as caregivers can promote their mental health and ultimately improve outcomes for their family members with disabilities.

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17. Nehir Yazici Ö, Şahin N, Özdemir Ç, Saruhan E, Topal H, Yazıcı T, Dombaycı Ö, Demirkan Başkaya G, Edgünlü T. Genetic Variations and Serum Levels of Leptin and Ghrelin in Autism Spectrum Disorder. Psychiatry Clin Psychopharmacol. 2024; 34(3): 221-8.

BACKGROUND: This study aims to examine leptin and ghrelin gene polymorphisms and serum levels in children with autism spectrum disorder (ASD). METHODS: The study comprised a case group of 40 children aged 2-7 diagnosed with ASD and a control group of 40 healthy children. The severity of ASD symptoms was assessed using the Childhood Autism Rating Scale and the Autism Behavior Checklist. Leptin and ghrelin gene variants were genotyped using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Serum ghrelin and leptin levels were measured using enzyme-linked immunosorbent assay kits. RESULTS: In this study, gene polymorphisms and allele frequencies were examined, and no significant difference was found (P > .05 for all). Our findings indicated no significant difference in leptin serum levels between the groups (P = .584). However, ghrelin serum levels were significantly lower in the ASD group (P = .027). Receiver operating curve analysis to determine the cutoff value of serum ghrelin level as a diagnostic indicator for ASD resulted in a cutoff value of 885.7 pg/mL with 42.50% sensitivity and 85% specificity (P = .021). No significant relationship was found between leptin and ghrelin serum levels and the severity of ASD (P > .05 for all). CONCLUSION: Our study is the first to evaluate leptin and ghrelin gene polymorphisms in ASD. Our findings indicate no association between leptin and ghrelin gene polymorphisms and ASD. However, our study suggests that ghrelin serum levels may potentially contribute to the etiology of ASD. More research is needed to understand the role of leptin and ghrelin in ASD.

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18. Nehzomi ZS, Shirani K. Investigating the role of food pollutants in autism spectrum disorder: a comprehensive analysis of heavy metals, pesticides, and mycotoxins. Naunyn Schmiedebergs Arch Pharmacol. 2024.

Food pollutants, including heavy metals, pesticides, and mycotoxins, have been proposed as potential risk factors for autism spectrum disorder (ASD) during pregnancy and early childhood. This paper examines the impact of food pollutants on ASD risk. A systematic search through PubMed, Google Scholar, and Sciverse yielded studies from 1990 to present. Research indicates elevated levels of heavy metals in children with ASD, linking pesticides and toxins to brain development disruptions. Mycotoxins, specifically, show a correlation with ASD and can contaminate food, posing a threat to neurodevelopment. Strategies like choosing organic foods and reducing exposure to toxins may benefit individuals with ASD and those vulnerable to the disorder. Further research is essential to comprehend the food pollutant-ASD relationship and devise effective exposure reduction strategies.

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19. Ouardouz M, Jasinski P, Khalife M, Mahoney JM, Hernan AE, Scott RC. Disrupted Hippocampal-Prefrontal Networks in a Rat Model of Fragile X Syndrome: A Study Linking Neural Dynamics to Autism-Like Behavioral Impairments. bioRxiv. 2024.

Fragile X Syndrome (FXS) is associated with autism spectrum disorder (ASD) symptoms that are associated with cognitive, learning, and behavioral challenges. We investigated how known molecular disruptions in the Fmr1 knockout (FMR-KO) rat model of FXS negatively impact hippocampal-prefrontal cortex (H-PFC) neural network activity and consequent behavior. METHODS: FMR-KO and control rats underwent a battery of behavioral tests assessing sociability, memory, and anxiety. Single-unit electrophysiology recordings were then conducted to measure patterns of neural activity in H-PFC circuit. Advanced mathematical models were used to characterize the patterns that were then compared between groups using generalized linear mixed models. RESULTS: FMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety, aligning with symptoms of ASD. At the neural level, these rats exhibited abnormal firing patterns in the H-PFC circuit that is critical for learning, memory, and social behavior. The neural networks in FMR-KO rats were also less densely connected and more fragmented, particularly in hippocampal-PFC correlated firing. These findings suggest that disruptions in neural network dynamics underlie the observed behavioral impairments in FMR-KO rats. CONCLUSION: FMR-KO significantly disrupts several characteristics of action potential firing in the H-PFC network, leading to deficits in social behavior, memory, and anxiety, as seen in FXS. This disruption is characterized by less organized and less resilient hippocampal-PFC networks. These findings suggest that therapeutic strategies aimed at normalizing neural dynamics, such as with brain stimulation, could potentially improve behavior and cognitive functions in autistic individuals. HIGHLIGHTS: Fragile X Syndrome is associated with autism, cognitive challenges and anxietyThe loss of Fmr1 protein disrupts processes involved in building neural networksThe consequence is abnormal neural dynamics in hippocampal-prefrontal cortex networksNormalization of dynamics could improve outcomes in FXS and ASD.

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20. Portillo NL, Thammathorn LP, Buitrago LM, Carter AS, Sheldrick RC, Eisenhower A. Disparities in Receipt of Early Intervention Services by Toddlers with Autism Diagnoses: an Intersectional Latent Class Analysis of Demographic Factors. J Autism Dev Disord. 2024.

We examined receipt of general early intervention services and autism-specific specialized services across demographic groups among toddlers with autism diagnoses who were receiving Part C Early Intervention (EI). Latent class analysis (n = 508) identified five demographically distinct subgroups associated with intersecting marginalization and privilege. Analyses of longitudinal parent interviews (n = 225) revealed service receipt disparities across these demographically distinct latent classes; children from White, U.S. born, English-proficient parents with incomes above poverty level received more EI services (M = 12.0 h/week) than other subgroups, with children from Latiné immigrant families receiving the fewest hours (M = 6.9 h/week). Across all groups, average intervention hours were 8.8 h/week. Despite early identification, racial, ethnic, and other sociodemographic disparities were evident in receipt of Part C Early Intervention services, indicating the need to address barriers to equitable care.

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21. Ragaglia B, Trovato I, Bulgarelli D. Peer-Mediated Social Skills Interventions in Primary School Settings for Autistic Children in the Light of the ICF Bio-psycho-social Model. A Systematic Review. J Autism Dev Disord. 2024.

This systematic review expands the current knowledge about Peer-Mediated Interventions (PMIs) for children with Autism Spectrum Disorder, focusing exclusively on primary school age (6-12 years). The study has three aims: (1) describing the main features of the PMI programs; (2) discussing the PMIs efficacy on autistic children’s social skills; (3) analyzing whether the PMIs were coherent with the bio-psycho-social model promoted by the International Classification of Functioning, Disability and Health (ICF) classification system, by referring to the person-environment interaction and to the concepts of body functions and structures, environmental factors, and activity and participation. The systematic review followed the PRISMA-P method. The literature search was conducted in August 2024 through PsycInfo, PsycArticles, Education Source, and PubMed databases. A total of 558 articles were generated; 1 study was later added. Twenty-four articles were finally included. Most of the studies used a multiple baseline design across subjects and proved to be effective. Yet, only 5 studies included a follow-up assessment, which showed contrasting results. PMIs partly fit the ICF bio-psycho-social vision, even if they were not designed for this purpose. Our analysis arises from the belief that systematically including the perspective of individual-environment interaction could better guarantee the intervention efficacy.

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22. Randall KN, Drew H, Gilman ES, Dixon E. Assistive Technology Uses and Barriers in the Home and Workplace for Adults With Intellectual and Developmental Disabilities. J Appl Res Intellect Disabil. 2025; 38(1): e13306.

BACKGROUND: Assistive technology (AT) has been successfully used by researchers and practitioners to increase task completion and independence in work and home environments for individuals with intellectual and developmental disabilities. While prior research has shown increased outcomes of incorporating AT into daily tasks, research has also indicated that actual use of AT in these settings is much lower. METHOD: The current qualitative study used semi-structured interviews with a sample of 25 adults (22 individuals with intellectual and developmental disabilities and three job coaches) to examine the perceived use and implementation of AT into home and work environments, along with potential challenges and barriers. Interviews were analyzed using a thematic analysis approach. RESULTS: Three themes were identified: (1) technologies used to support daily living skills, (2) technologies used to support employment and (3) challenges and barriers to using technologies. CONCLUSIONS: Findings indicate that while individuals with intellectual and developmental disabilities are using a variety of AT in their homes both successfully and independently, they have extremely limited use in their workplaces. Implications for practice and future research are discussed.

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23. Rausch J, Fangmeier T, Falter-Wagner CM, Ackermann H, Espelöer J, Hölzel LP, Riedel A, Ritvo A, Vogeley K, van Elst LT. A novel screening instrument for the assessment of autism in German language: validation of the German version of the RAADS-R, the RADS-R. Eur Arch Psychiatry Clin Neurosci. 2024.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) demonstrated excellent results in its original study, with a sensitivity of 97% and a specificity of 100% (Ritvo et al. in J Autism Dev Disord 41:1076-1089, 2011). As a result, it was included in the National Institute for Health and Care Excellence (NICE) guidelines (Recommendations | Autism spectrum disorder in adults: diagnosis and management | Guidance | NICE, 2022). The questionnaire includes 80 questions across four subcategories (language, social relatedness, circumscribed interests, sensory motor). So far, the subcategory sensory motor has not been addressed in most available instruments, despite being part of the diagnostic criteria specified in DSM-5 (Falkai et al., in Diagnostisches Und Statistisches Manual Psychischer Störungen DSM-5. Hogrefe, 2015) and ICD-11 (ICD-11 for Mortality and Morbidity Statistics, 2022). In our validation study, we tested a translated German version of the questionnaire in 299 individuals (110 persons with ASD according to ICD-10 F84.0, F84.5, 64 persons with an primary mental disorders (PMD), 125 persons with no disorders). To enhance the practical use of the instrument in clinical everyday practice, the questionnaire was completed by the participants without the presence of a clinician-unlike the original study. Psychiatric diagnoses were established following the highest standards, and psychometric properties were calculated using established protocols. The German version of the RADS-R yielded very good results, with a high sensitivity of 92.5% and a high specificity of 93.6%. The area under the curve (AUC = 0.976), indicates a high quality and discriminatory power of RADS-R. Furthermore, the ROC curve analysis showed that the optimal threshold to distinguish between the ASD and non-ASD groups in the German version of the RAADS-R is a score of 81. In comparison to the RADS-R, the co-administered instruments Social Responsiveness Scale (SRS), Autism Spectrum Quotient (AQ), and Empathy Quotient (EQ) each showed slightly better specificity but worse sensitivity in this sample.The study included individuals already diagnosed with ASD according to ICD-10 (F84.0, F84.5), with or without an primary mental disorders, preventing us from identifying the influence of comorbidities on the RADS-R results. In addition, a self-report questionnaire has generally only limited objectivity and may allow for false representation of the symptoms. The RADS-R compares well with other questionnaires and can provide valuable additional information. It could turn out to be a helpful diagnostic tool for patients in Germany. We propose naming the German version RADS-R (Ritvo Autism Diagnostic Scale – rRevised) to reflect the change in terminology.

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24. Salia S, Burke FF, Hinks ME, Randell AM, Matheson MA, Walling SG, Swift-Gallant A. Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes. Brain Behav Immun. 2024; 123: 813-23.

The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.

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25. Schichter I, Nadwodny N, Kohn BH, Thakkar D, Pantalone DW, Faja S. Exploring social cognition and romantic self-efficacy in autistic young adults: Better social awareness is associated with lower confidence. Res Autism Spectr Disord. 2024; 118.

BACKGROUND: Despite misconceptions, autistic young adults are interested in romantic relationships (Fernandes et al., 2016; Hancock et al., 2019; Mehzabin & Stokes, 2011). Research is needed to better understand how the social characteristics of autism impact romantic relationship experiences, knowledge of sexual health, and confidence in one’s own abilities. Social cognition skills are linked to functioning in interpersonal relationships and are important for understanding the mental states of others. The present research aims to explore the intersections among social cognition skills, romantic self-efficacy, perceived knowledge, and dating outcomes. We hypothesize that social cognition skill level, self-efficacy, perceived knowledge, and romantic relationship outcomes will be positively related. METHOD: Verbal autistic young adults (N = 31) aged 18-26 years participated in a study aimed at investigating the romantic experiences of young autistic adults. Participants completed questionnaires on self-efficacy and perceived knowledge, as well as a battery of social cognition tasks, including assessments of spontaneous and non-spontaneous social cognition. RESULTS: Spontaneous social cognition was negatively correlated with both relationship self-efficacy and perceived knowledge. Perceived knowledge, actual knowledge, and self-efficacy were positively correlated with each other. CONCLUSION: This exploratory study was the first of which we are aware to demonstrate that autistic adults with stronger spontaneous social awareness are less confident of their sexual knowledge and abilities in romantic relationships than autistic adults with weaker spontaneous awareness. These findings suggest social cognitive tasks could be useful in assessing the specific sexual and romantic health-education needs of young autistic adults.

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26. Sharp WG. Systematic Reviews on Eating Disorders and Autism Spectrum Disorder Emphasize a Call to Further Expand High-Quality Research. Int J Eat Disord. 2024.

Two recent systematic reviews provide important insights into the current state of the eating disorder literature regarding autistic traits, ASD prevalence, and experience with accessing treatment, with a specific focus on anorexia nervosa (AN). The extant literature provides converging evidence for elevated autistic traits in individuals with AN, while evidence for increased prevalence of ASD in AN is less robust. Presence of autistic traits or a formal ASD diagnosis both appear to elevate the potential for a more complicated experience during eating disorder treatment. Together, this work provides compelling justification to expand the breadth of inquiry regarding eating disorders and ASD, with a specific call for increased methodological rigor when designing and conducting future research. My commentary calls for specific steps to advance our understanding of ASD and eating disorders.

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27. St Victor R, Mulakalapalli S, Park Y, Daly E. Rise in Autism Spectrum Disorder Diagnoses: A Comparative Analysis of Pre-pandemic and Pandemic Periods. Cureus. 2024; 16(9): e70167.

Introduction This study analyzes the rise in autism spectrum disorder (ASD) diagnoses by comparing pre-pandemic (2017-2019) and pandemic period (2021-2023) data from two private pediatric practices with different populations in New York. The year 2020 was out of the analysis to focus on the impact after the shutdowns on ASD, and there were disruptions in clinic operations during that year. Clinic I primarily served an African-American ethnic population, while Clinic II primarily served an Asian population. Methods A retrospective analysis was conducted using de-identified patient numbers from the electronic medical records (EMR) of two private clinics. Only the numbers of new patients diagnosed each year were included from January 1, 2017, to December 31, 2019 (pre-pandemic), and January 1, 2021, to December 31, 2023 (pandemic). Sixteen ASD International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes were included in this analysis. Descriptive and inferential statistics were used to find important patterns and determine statistical significance. Results The study included 537 patients, 182 from Clinic I and 355 from Clinic II. Clinic I demonstrated a significant increase in ASD diagnoses, from 63 (pre-pandemic) to 119 (pandemic) (χ2=17.23; p=0.000033). Clinic II demonstrated a significant increase in ASD diagnoses, from 149 (pre-pandemic) to 206 (pandemic) (χ2=9.15; p=0.00248). Conclusion The significant increase in ASD diagnoses in two private pediatric practices with different populations indicates a notable association with the shutdown periods and the pandemic. Factors such as disrupted routines, changes in access to healthcare services, and increased parental awareness may have contributed to this rise. Further longitudinal studies are needed to understand the long-term impacts of the pandemic on ASD diagnoses and care.

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28. Suh JH, Han SJ, Choi SA, Yang H, Park S. Tablet computer-based cognitive training for visuomotor integration in children with developmental delay: a pilot study. BMC Pediatr. 2024; 24(1): 683.

BACKGROUND: Impaired visuomotor integration (VMI) is commonly observed in children with developmental delay (DD). This pilot study aimed to evaluate the effects of tablet computer-based cognitive training on the VMI in children with DD. METHODS: This study included children aged 4 to under 18 years diagnosed with DD. The children participated in a 12-week tablet computer-based visual-spatial and visuomotor training program. They were administered the Mind Rx Kids Program (Brain Academy, Seoul, South Korea). The participants underwent daily 30-min tablet computer-based training for 12 weeks. The primary visuomotor function was measured using the Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6). For secondary outcomes, measurements were taken before and after 12-week treatment using the Quality of Upper Extremity Skills Test (QUEST), Functional Independence Measure for Children (WeeFIM), Childhood Autism Rating Scale (CARS), Attention deficit hyperactivity disorder Rating Scale (ARS), and Child Smartphone Addiction Observer Scale. The Wilcoxon signed-rank test was used to compare the pre- and post-treatment outcomes. RESULTS: Ten children with DD participated in this study. The results of the 12-week tablet computer-based cognitive training showed significant improvements in the raw score, standard score, percentile score, and equivalent age of the Beery VMI-6. Additionally, there were significant improvements in QUEST and WeeFIM scores. Although there were improvements in the CARS, ARS, and smartphone addiction observer scale, these were not statistically significant. CONCLUSION: This pilot study confirmed that applying tablet computer-based cognitive training to children with DD not only improves VMI, but also enhances fine motor skills and activities of daily living. Furthermore, the results of this study indicate that tablet computer-based cognitive training does not increase digital media addiction. Therefore, children with DD can engage in tablet computer-based cognitive training at home without concerns about digital media addiction.

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29. Ustun Gullu B, Oztop DB, Umutlu Aydin E, Ors B, Cikili Uytun M, Yurumez E. Interactions between autistics and healthy children and their parents in emotional availability: a comparative study. Glob Ment Health (Camb). 2024; 11: e93.

In this study, we assessed the interactions of mothers and fathers with their children diagnosed with autism spectrum disorder (ASD) in terms of emotional availability (EA) and compared them with the interactions of healthy controls. Children, aged 13-60 months and applied to the Infant Mental Health Unit between January 2019 and March 2021 and their parents without any clinical diagnosis, were included. The EA levels of mothers and fathers of the autistic group, which included 30 boys and 13 girls, and those of the control group, which included 10 boys and 10 girls, were compared. According to the results obtained, it was determined that the EA levels of mothers and fathers of healthy controls were not different; however, the mothers were more sensitive and better in structuring the content of play compared with the fathers in the ASD group. It was noted that the fathers of children with ASD were more hostile than the mothers. EA should be taken as a criterion to determine the intensity and content of treatment, particularly in ASD. Additionally, increased awareness of fathers in EA may provide better results in the intervention process.

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30. Yamashita R, Iwasa Y, Hashimoto T. Developmental Changes in Stroop Task Performance among Individuals with High-Functioning Pervasive Developmental Disorders. J Med Invest. 2024; 71(3.4): 254-9.

OBJECTIVE: This study aimed to assess age-related changes in Stroop Color and Word test indices in individuals with high-functioning pervasive developmental disorder (HF-PDD) and compare their performance with typically developing (TD) individuals. METHODS: There were a total of 125 participants (57 TD, 68 HF-PDD), aged 6-24. Stimuli were displayed on computer screens, and participants verbally responded with response times recorded via voice key function. RESULTS: Single regression analysis revealed age-associated trends in Stroop test indices for both groups, indicating shorter response times and reduced Stroop interference with age. The age at which the best Stroop test results were obtained ranged from 220 to 260 months for TD and from 195 to 201 months for HF-PDD. While color naming and word reading tasks showed no significant group differences, color word naming task response times were significantly longer for the HF-PDD group. Around 30% of HF-PDD participants scored over two standard deviations above the TD mean. CONCLUSIONS: Both TD and HF-PDD groups exhibited age-related changes in Stroop task performance, which were fitted by a quadratic regression curve. Prolongation of the color word naming task in the HF-PDD group suggests that approximately 30% of individuals with HF-PDD have difficulty with stereotype suppression. J. Med. Invest. 71 : 254-259, August, 2024.

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31. Yuxi R, Shuqi J, Cong L, Shufan L, Yueyu L. A systematic review of the effect of sandplay therapy on social communication deficits in children with autism spectrum disorder. Front Pediatr. 2024; 12: 1454710.

OBJECTIVE: To explore the efficacy of sandplay therapy in intervening social communication deficits in children with autism spectrum disorders (ASD), and whether this efficacy is influenced by the age of the children and the dosage of sandplay therapy intervention. METHODS: Following the PICOS principle, randomized controlled trials (RCTs) related to sandplay therapy for social communication deficits in ASD children were retrieved from seven databases: PubMed, WOS, The Cochrane Library, Embase, CNKI, Wanfang, and VIP, from the inception of each database to November 10, 2023. Two experimenters independently conducted study screening and excluded studies with concomitant diseases, incomplete data, unextractable data, and non-randomized controlled trials. The PEDro scale was used for methodological quality assessment, and the GRADEprofiler method was employed to evaluate the quality of evidence. Stata17 software was used for meta-analysis, subgroup analysis, sensitivity analysis, and publication bias testing. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as the effect statistics. RESULTS: A total of 12 RCTs (791 cases) were included. Sandplay therapy had a positive impact on the social communication deficits of ASD children [SMD = -1.42, 95%CI (-1.79, -1.04), P < 0.001]. Subgroup analysis revealed that sandplay therapy administered during the early school age (449 cases, SMD = -1.44, P < 0.05), for a duration of 22-28 weeks (208 cases, SMD = 1.69, P < 0.05), and with a frequency of once per week (218 cases, SMD = -1.67, P < 0.05) was most effective in improving on social communication deficits of ASD children. DISCUSSION: The quality of evidence in this study was rated as high, with good methodological quality, including 12 studies with better quality and no detection of bias risk. The study had high heterogeneity, which was attributed to the measurement tools and intervention duration through subgroup analysis, with no inconsistency found. Additionally, no downgrade factors related to imprecision, publication bias, or indirectness were identified. In conclusion, sandplay therapy is an effective measure to improve social communication deficits in children with ASD, and current evidence recommends early intervention using an individual sandplay therapy or integrated sandplay therapy intervention program once a week for 22-28 weeks, which can serve as evidence-based clinical guidance. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk, identifier (CRD420234821750).

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32. Zhang Y, Chen Y, Li W, Tang L, Li J, Feng X. Targeting the circadian modulation: novel therapeutic approaches in the management of ASD. Front Psychiatry. 2024; 15: 1451242.

Circadian dysfunction is prevalent in neurodevelopmental disorders, particularly in autism spectrum disorder (ASD). A plethora of empirical studies demonstrate a strong correlation between ASD and circadian disruption, suggesting that modulation of circadian rhythms and the clocks could yield satisfactory advancements. Research indicates that circadian dysfunction associated with abnormal neurodevelopmental phenotypes in ASD individuals, potentially contribute to synapse plasticity disruption. Therefore, targeting circadian rhythms may emerge as a key therapeutic approach. In this study, we did a brief review of the mammalian circadian clock, and the correlation between the circadian mechanism and the pathology of ASD at multiple levels. In addition, we highlight that circadian is the target or modulator to participate in the therapeutic approaches in the management of ASD, such as phototherapy, melatonin, modulating circadian components, natural compounds, and chronotherapies. A deep understanding of the circadian clock’s regulatory role in the neurodevelopmental phenotypes in ASD may inspire novel strategies for improving ASD treatment.

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