1. Ambigapathy R, Ramachandram S, Rahim FF. Referral patterns and outcomes of children who failed Modified Checklist for Autism in Toddlers screening during routine health screening at maternal and child health clinics in the northeast district of Penang: A retrospective cohort study. Malays Fam Physician;2024;19:9.

INTRODUCTION: Autism spectrum disorder (ASD) is a developmental disability that causes significant social, communication and behavioural challenges. The Modified Checklist for Autism in Toddlers (M-CHAT) is a parent-administered screening questionnaire for ASD used at 18 and 36 months of age. This study aimed to determine the outcomes of children who failed M-CHAT screening during routine health screening at maternal and child health clinics in northeast district, Penang and the prevalence of ASD among those with a final diagnosis. METHODS: This retrospective cohort study was conducted at 12 maternal and child health clinics. All children who failed M-CHAT screening at 18 and 36 months from January 2017 to December 2021 and received a final diagnosis before 31 March 2022 were recruited. All information required was recorded in a data collection form and analysed using SPSS. Multiple logistic regression was performed to assess the association between the factors and ASD status. RESULTS: Eighty-two children failed M-CHAT screening. Fifty children did not receive a final diagnosis. Among 32 children who received a final diagnosis, 25 were diagnosed with ASD (78.1%). Among the children who underwent M-CHAT screening, the odds of having ASD increased by a factor of 1.2 for every 1-unit increase in age at final diagnosis. CONCLUSION: In northeast district, Penang, more than half of children who fail M-CHAT screening have no final diagnosis. The specificity of the M-CHAT is 78.1% among children with a final diagnosis of ASD. The age at final diagnosis is positively associated with the diagnosis of ASD.

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2. Arsham S, Razeghi R, Movahedi A. Errorless Training Benefits Motor Learning and Kinematic Outcomes in Children With Autism Spectrum Disorders. Percept Mot Skills;2024 (Mar 18):315125241238308.

Most children with Autism Spectrum Disorder (ASD) have some form of motor deficits. Additionally, based on executive dysfunction, working memory is often atypical in these children. Errorless learning reduces demands on working memory. In this study, we investigated the effectiveness of errorless training on these children’s ability to learn golf putting. Participants (N = 20), aged 9-13 years (M (=) 10.15, SD (=) 1.4), were randomly assigned to either: (a) an errorless (ER) training group (n = 10) or (b) an explicit instruction (EI) group (n = 10). The ER group practiced putting from different distances without any instruction, while the EI group practiced putting at a particular distance with instruction. We measured motor performance (e.g., putting accuracy) and kinematic variables (e.g., putter face angle). One-way analyses of variance showed that motor performance significantly improved in both groups, but that the ER group showed significantly better accuracy retention (p < .028) and transfer learning (p < .047) than the instructional group. Kinematic variables were also significantly different between the two groups on the transfer test. These findings supported the benefits of errorless training compared to explicit instruction to teach motor skills to children with ASD.

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3. Assary E, Oginni OA, Morneau-Vaillancourt G, Krebs G, Peel AJ, Palaiologou E, Lockhart C, Ronald A, Eley TC. Genetics of environmental sensitivity and its association with variations in emotional problems, autistic traits, and wellbeing. Mol Psychiatry;2024 (Mar 18)

Greater environmental sensitivity has been associated with increased risk of mental health problems, especially in response to stressors, and lower levels of subjective wellbeing. Conversely, sensitivity also correlates with lower risk of emotional problems in the absence of adversity, and in response to positive environmental influences. Additionally, sensitivity has been found to correlate positively with autistic traits. Individual differences in environmental sensitivity are partly heritable, but it is unknown to what extent the aetiological factors underlying sensitivity overlap with those on emotional problems (anxiety and depressive symptoms), autistic traits and wellbeing. The current study used multivariate twin models and data on sensitivity, emotional problems, autistic traits, and several indices of psychological and subjective wellbeing, from over 2800 adolescent twins in England and Wales. We found that greater overall sensitivity correlated with greater emotional problems, autistic traits, and lower subjective wellbeing. A similar pattern of correlations was found for the Excitation and Sensory factors of sensitivity, but, in contrast, the Aesthetic factor was positively correlated with psychological wellbeing, though not with emotional problems nor autistic traits. The observed correlations were largely due to overlapping genetic influences. Importantly, genetic influences underlying sensitivity explained between 2 and 12% of the variations in emotional problems, autistic traits, and subjective wellbeing, independent of trait-specific or overlapping genetic influences. These findings encourage incorporating the genetics of environmental sensitivity in future genomic studies aiming to delineate the heterogeneity in emotional problems, autistic traits, and wellbeing.

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4. Azadboni TT, Nasiri S, Khenarinezhad S, Sadoughi F. Effectiveness of serious games in social skills training to Autistic individuals: A systematic review. Neurosci Biobehav Rev;2024 (Mar 15):105634.

Autism Spectrum Disorder (ASD) is a complex neurological condition that significantly impacts individuals’ daily lives and social interactions due to challenges in verbal and non-verbal communication. Game-based tools for psychological support and patient education are rapidly gaining traction. Among these tools, teaching social skills via serious games has emerged as a particularly promising educational strategy for addressing specific characteristics associated with autism. Unlike traditional games, serious games are designed with a dual purpose: to entertain and to fulfill a specific educational or therapeutic goal. This systematic review aims to identify and categorize serious computer games that have been used to teach social skills to autistic individuals and to assess their effectiveness. We conducted a comprehensive search across seven databases, resulting in the identification and analysis of 25 games within 26 studies. Out of the 104 criteria assessed across these studies, 57 demonstrated significant improvement in participants. Furthermore, 22 of these studies reported significant enhancements in at least one measured criterion, with 13 studies observing significant improvements in all assessed outcomes. These findings overwhelmingly support the positive impact of computer-based serious game interventions in teaching social skills to autistic individuals.

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5. Barba-Vila O, García-Mieres H, Ramos B. Probiotics in autism spectrum disorders: a systematic review of clinical studies and future directions. Nutr Rev;2024 (Mar 18)

CONTEXT: It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses. OBJECTIVE: To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies. DATA SOURCES: The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases. DATA EXTRACTION: Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials. RESULTS: The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies. CONCLUSIONS: Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.

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6. Bedford SA, Ortiz-Rosa A, Schabdach JM, Costantino M, Tullo S, Piercy T, Lai MC, Lombardo MV, Di Martino A, Devenyi GA, Chakravarty MM, Alexander-Bloch AF, Seidlitz J, Baron-Cohen S, Bethlehem RAI. The impact of quality control on cortical morphometry comparisons in autism. Imaging Neurosci (Camb);2023 (Oct 1);1:1-21.

Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories. Here, we evaluate whether the quality of surface reconstructions by FreeSurfer (one of the most widely used MRI processing pipelines) interacts with clinical and demographic factors. We present a tool, FSQC, that enables quick and efficient yet thorough assessment of outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, two other manual ratings of raw image quality, and two popular automated QC methods. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does not eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons.

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7. Benson-Goldberg S, Geist L, Erickson K. Simplified COVID-19 guidance for adults with intellectual and developmental disabilities. J Appl Res Intellect Disabil;2024 (May);37(3):e13222.

BACKGROUND: During the COVID-19 pandemic, the United States’ Centers for Disease Control and Prevention (CDC) created guidance documents that were too complex to be read and understood by the majority of adults with intellectual and developmental disabilities who often read at or below a third-grade reading level. This study explored the extent to which these adults could read and understand CDC documents simplified using Minimised Text Complexity Guidelines. METHOD: This study involved 20 participants, 18-48 years of age. Participants read texts and responded to multiple-choice items and open-ended questions to gather information about how they interacted with and understood the texts. RESULTS: The results provide initial evidence that the Minimised Text Complexity Guidelines resulted in texts that participants could read and understand. CONCLUSION: Implications for increasing the accessibility of public health information so that it can be read and understood by adults with extremely low literacy skills are discussed.

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8. Bijlani S, Pang KM, Bugga LV, Rangasamy S, Narayanan V, Chatterjee S. Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome. Front Genome Ed;2024;6:1346781.

Rett syndrome is an acquired progressive neurodevelopmental disorder caused by de novo mutations in the X-linked MECP2 gene which encodes a pleiotropic protein that functions as a global transcriptional regulator and a chromatin modifier. Rett syndrome predominantly affects heterozygous females while affected male hemizygotes rarely survive. Gene therapy of Rett syndrome has proven challenging due to a requirement for stringent regulation of expression with either over- or under-expression being toxic. Ectopic expression of MECP2 in conjunction with regulatory miRNA target sequences has achieved some success, but the durability of this approach remains unknown. Here we evaluated a nuclease-free homologous recombination (HR)-based genome editing strategy to correct mutations in the MECP2 gene. The stem cell-derived AAVHSCs have previously been shown to mediate seamless and precise HR-based genome editing. We tested the ability of HR-based genome editing to correct pathogenic mutations in Exons 3 and 4 of the MECP2 gene and restore the wild type sequence while preserving all native genomic regulatory elements associated with MECP2 expression, thus potentially addressing a significant issue in gene therapy for Rett syndrome. Moreover, since the mutations are edited directly at the level of the genome, the corrections are expected to be durable with progeny cells inheriting the edited gene. The AAVHSC MECP2 editing vector was designed to be fully homologous to the target MECP2 region and to insert a promoterless Venus reporter at the end of Exon 4. Evaluation of AAVHSC editing in a panel of Rett cell lines bearing mutations in Exons 3 and 4 demonstrated successful correction and rescue of expression of the edited MECP2 gene. Sequence analysis of edited Rett cells revealed successful and accurate correction of mutations in both Exons 3 and 4 and permitted mapping of HR crossover events. Successful correction was observed only when the mutations were flanked at both the 5′ and 3′ ends by crossover events, but not when both crossovers occurred either exclusively upstream or downstream of the mutation. Importantly, we concluded that pathogenic mutations were successfully corrected in every Rett line analyzed, demonstrating the therapeutic potential of HR-based genome editing.

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9. Feller C, Ilen L, Eliez S, Schneider M. Social skills in neurodevelopmental disorders: a study using role-plays to assess adolescents and young adults with 22q11.2 deletion syndrome and autism spectrum disorders. J Neurodev Disord;2024 (Mar 18);16(1):11.

BACKGROUNDS: Social skills are frequently impaired in neurodevelopmental disorders and genetic conditions, including 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). Although often assessed with questionnaires, direct assessment provides a more valid estimate of the constructs. Role-plays (i.e., simulates situational settings) therefore appear to be an appropriate indicator of social skills in daily life. METHODS: This co-registered study involved 53 individuals with 22q11DS, 34 individuals with ASD, and 64 typically developing (TD) peers aged 12-30 years. All participants were assessed with role-plays as well as parent-reported questionnaires and clinical interviews focusing on social skills, functioning and anxiety. RESULTS: Both clinical groups showed impaired social skills compared to TD, but distinct social profiles emerged between the groups. Individuals with 22q11DS displayed higher social appropriateness and clarity of speech but weaker general argumentation and negotiation skills, with the opposite pattern observed in participants with ASD. No association was found between social skills measured by direct observation and caregiver reports. Social anxiety, although higher in clinical groups than in TD, was not associated with role-plays. CONCLUSIONS: This study highlights the need to train social skills through tailored interventions to target the specific difficulties of each clinical population. It also highlights the importance of combining measures as they do not necessarily provide the same outcome.

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10. Goldfarb Y, Assion F, Begeer S. Where do autistic people work? The distribution and predictors of occupational sectors of autistic and general population employees. Autism;2024 (Mar 18):13623613241239388.

Studies on employment of autistic individuals mainly assessed if they work and what their working conditions are (e.g. weekly hours, salary) while less is known about where they work. We explore this issue in our study, by examining which employment sectors do autistic adults work in, and comparing them to the general workforce in the Netherlands. We also explored the possibility that gender, age, age at diagnosis, level of education, degree of autistic traits and presence of focused interests could lead to a higher likelihood of working in specific sectors. We assessed data from a survey filled in by 1115 employed autistic adults (476 male; 627 female; 12 other; mean age: 40.75). Dutch workforce information was based on data form the Central Bureau of Statistics. Results showed that a higher proportion of autistic employees worked in healthcare & welfare, information technology, and the public-army-charity sectors. These were the three most-common sectors for this group. A lower proportion of autistic employees worked in economics & finances, and industry & construction, compared to the general workforce. Most autistic employees in the healthcare & welfare sector were females while having a higher educational degree and being male increased the chance of working in information technology. In addition to the common impression that most autistic individuals have interests or abilities that align with employment in information technology and technology sectors, we found that autistic employees worked in various sectors. It is important to address individual characteristics and needs of autistic individuals, while encouraging diverse employment opportunities.

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11. Li W, Liu C, Chen S. Associations between genetically determined dietary factors and risk of autism spectrum disorder: a Mendelian randomization study. Front Nutr;2024;11:1210855.

BACKGROUND: Existing studies confirm the importance of dietary factors in developing autism spectrum disorder (ASD) and disease progression. Still, these studies are primarily observational, and their causal relationship is unknown. Moreover, due to the extensive diversity of food types, the existing research remains somewhat limited in comprehensiveness. The inconsistency of the results of some studies is very disruptive to the clinic. This study infers a causal relationship between dietary factors on the risk of developing ASD from a genetic perspective, which may lead to significant low-cost benefits for children with ASD once the specificity of dietary factors interfering with ASD is confirmed. METHODS: We performed a two-sample Mendelian randomization (MR) analysis by selecting single nucleotide polymorphisms (SNPs) for 18 common dietary factors from the genome-wide association study (GWAS) database as instrumental variables (IVs) and obtaining pooled data for ASD (Sample size = 46,351) from the iPSYCH-PGC institution. Inverse variance weighted (IVW) was used as the primary analytical method to estimate causality, Cochran’s Q test to assess heterogeneity, the Egger-intercept test to test for pleiotropy and sensitivity analysis to verify the reliability of causal association results. RESULTS: The MR analysis identified four dietary factors with potential causal relationships: poultry intake (fixed-effects IVW: OR = 0.245, 95% CI: 0.084-0.718, P < 0.05), beef intake (fixed-effects IVW: OR = 0.380, 95% CI: 0.165-0.874, P < 0.05), cheese intake (random-effects IVW: OR = 1.526, 95% CI: 1.003-2.321, P < 0.05), and dried fruit intake (fixed-effects IVW: OR = 2.167, 95% CI: 1.342-3.501, P < 0.05). There was no causal relationship between the remaining 14 dietary factors and ASD (P > 0.05). CONCLUSION: This study revealed potential causal relationships between poultry intake, beef intake, cheese intake, dried fruit intake, and ASD. Poultry and beef intake were associated with a reduced risk of ASD, while cheese and dried fruit intake were associated with an increased risk. Other dietary factors included in this study were not associated with ASD.

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12. McNaughton KA, Moss A, Yarger HA, Redcay E. Smiling synchronization predicts interaction enjoyment in peer dyads of autistic and neurotypical youth. Autism;2024 (Mar 18):13623613241238269.

For autistic and neurotypical youth, having positive social interactions with other youth is an important part of well-being. Other researchers have found that one factor that can make people feel like social interactions have gone well is synchronization. Synchronization happens when peoples’ body movements and facial expressions align while they’re interacting. We focus on smiling synchronization here because other studies have found that when neurotypical individuals synchronize their smiles more in a social interaction, they say they enjoy that social interaction more. However, no studies have directly tested whether smiling synchrony influences social interaction enjoyment in autistic and neurotypical youth. We measured smiling synchrony in pairs of interacting autistic and neurotypical youth who were meeting each other for the first time. Some pairs were autistic youth interacting with other autistic youth (autistic with autistic participant pairs), some pairs were autistic youth interacting with neurotypical youth (autistic with neurotypical participant pairs), and other pairs were neurotypical youth interacting with neurotypical youth (neurotypical with neurotypical participant pairs). We found that autistic with neurotypical participant pairs had lower smiling synchrony than neurotypical with neurotypical participant pairs. Youth who were in dyads that had more smiling synchrony said they enjoyed interacting with their partner more and that they wanted to interact with their partner again. Our research shows that smiling synchrony is one part of interactions between autistic and neurotypical youth that influences how well youth say the interaction went. Identifying natural opportunities for autistic and neurotypical youth to share positive feelings could be one way to promote positive social interactions between autistic and neurotypical youth.

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13. Neul JL, Benke TA, Marsh ED, Lane JB, Lieberman DN, Skinner SA, Glaze DG, Suter B, Heydemann PT, Beisang AA, Standridge SM, Ryther RCC, Haas RH, Edwards LJ, Ananth A, Percy AK. Distribution of hand function by age in individuals with Rett syndrome. Ann Child Neurol Soc;2023 (Sep);1(3):228-238.

OBJECTIVE: To determine the longitudinal distribution of hand function skills in individuals with classic Rett Syndrome (RTT), an X-linked dominant neurodevelopmental disorder, and correlate with MECP2 variants. METHOD: We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus in this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific MECP2 variant groups. RESULTS: Following the initial regression period, hand function continues to decline across the age spectrum in individuals with RTT. Specific differences are noted with steeper declines in hand function among those with milder variants (Group A: R133C, R294X, R306C, and C-terminal truncations) compared to groups composed of individuals with more severe variants. CONCLUSIONS: These temporal variations in hand use represent specific considerations which could influence the design of clinical trials that test therapies aiming to ameliorate specific functional limitations in individuals with RTT. Furthermore, the distinct impact of specific MECP2 variants on clinical severity, especially related to hand use, should be considered in such interventional trials.

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14. Ramazani Z, Nakhaee S, Sharafi K, Rezaei Z, Mansouri B. Autism spectrum disorder: Cadmium and mercury concentrations in different biological samples, a systematic literature review and meta-analysis of human studies. Heliyon;2024 (Mar 30);10(6):e27789.

The present study was conducted to investigate the differences in cadmium (Cd) and mercury (Hg) concentrations between children with autism spectrum disorder (ASD) and controls. In this systematic review and meta-analysis study, three thousand one hundred forty-five studies were collected from scientific databases including Web of Science, Scopus, PubMed, and Google Scholar from January 2000 to October 2022 and were investigated for eligibility. As a result, 37 studies published in the period from 2003 to 2022 met our inclusion criteria and were considered in the meta-analysis. The heterogeneity assumption was evaluated using the Chi-squared-based Q-test and I-squared (I(2)) statistics. The pooled estimates were shown in the forest plots with Hedges’ g (95% confidence interval) values. The random effects model demonstrated that there is no significant difference in the blood (Hedges’ g: 0.14, 95% CI: 0.45, 0.72, p > 0.05), hair (Hedges’ g: 0.12, 95% CI: 0.26, 0.50, p > 0.05), and urinary (Hedges’ g: 0.05, 95% CI: 0.86, 0.76, p > 0.05) Cd levels of the case group versus control subjects. Moreover, the pooled findings of studies showed no significant difference in the blood (Hedges’ g: 1.69, 95% CI: 0.09, 3.48, p > 0.05), hair (Hedges’ g: 3.42, 95% CI: 1.96, 8.80, p > 0.05), and urinary (Hedges’ g: 0.49, 95% CI: 1.29 – 0.30, p > 0.05) Hg concentrations. The results demonstrated no significant differences in Hg and Cd concentrations in different biological samples of children with ASD compared to control subjects.

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15. Su WC, Mutersbaugh J, Huang WL, Bhat A, Gandjbakhche A. Developmental Differences in Reaching-and-Placing Movement and Its Potential in Classifying Children with and without Autism Spectrum Disorder: Deep Learning Approach. Res Sq;2024 (Mar 4)

Autism Spectrum Disorder (ASD) is among the most prevalent neurodevelopmental disorders, yet the current diagnostic procedures rely on behavioral analyses and interviews and lack objective screening methods. This study seeks to address this gap by integrating upper limb kinematics and deep learning methods to identify potential biomarkers that could be validated in younger age groups in the future to enhance the identification of ASD. Forty-one school-age children, with and without an ASD diagnosis (Mean age ± SE = 10.3 ± 0.4; 12 Females), participated in the study. A single Inertial Measurement Unit (IMU) was affixed to the child’s wrist as they engaged in a continuous reaching and placing task. Deep learning techniques were employed to classify children with and without ASD. Our findings suggest delays in motor planning and control in school-age children compared to healthy adults. Compared to TD children, children with ASD exhibited poor motor planning and control as seen by greater number of movement units, more movement overshooting, and prolonged time to peak velocity/acceleration. Compensatory movement strategies such as greater velocity and acceleration were also seen in the ASD group. More importantly, using Multilayer Perceptron (MLP) model, we demonstrated an accuracy of ~ 78.1% in classifying children with and without ASD. These findings underscore the potential use of studying upper limb movement kinematics during goal-directed arm movements and deep learning methods as valuable tools for classifying and, consequently, aiding in the diagnosis and early identification of ASD upon further validation in younger children.

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16. Sutherland D, Griffin J, Flynn S, Thompson PA, Hastings RP. Positive family connections for families of children with a developmental disability: Cluster randomized controlled trial. J Fam Psychol;2024 (Mar 18)

Positive Family Connections is a coproduced, positively oriented, family-systems program for families of children with a developmental disability aged 8-13 years. The study was a feasibility cluster randomized-controlled trial which was registered prospectively (International Standard Randomised Controlled Trial Number 14809884). Families (clusters) were randomized 1:1 to take part in Positive Family Connections immediately or to a waitlist condition and were followed up 4 months and 9 months after randomization. Feasibility outcomes included participant and facilitator recruitment rates, retention, intervention adherence, and fidelity. The proposed primary outcome measure was the family APGAR, a measure of family functioning. Quantitative data were analyzed using multilevel modeling. Sixty families (60 primary parental carers and 13 second carers) were randomized. 73.33% of primary parental carers and 71.43% of second carers in the intervention group attended ≥ 4 intervention sessions, and fidelity of delivery was high (M = 94.02% intervention components delivered). Retention for the proposed primary outcome was 97.26% at 4-month follow-up and 98.63% at 9-month follow-up. Intervention condition was not associated with family APGAR scores at 9-month follow-up (estimate = 0.06, 95% CI [-0.49, 0.61], p = .86, Hedges’ g = 0.03, 95% CI [-0.43, 0.49]). However, meaningful improvements were observed for other secondary outcomes related to parental well-being and family relationships. A definitive randomized-controlled trial of Positive Family Connections is feasible. Preliminary evaluation of outcomes shows that Positive Family Connections may be beneficial for parental psychological well-being and family relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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17. Szlamka Z, Sebastián C, Hanlon C, Hoekstra RA. Caregiver-centred empowerment for families raising autistic children: A qualitative case study from Argentina. Autism;2024 (Mar 18):13623613241238254.

Caregivers of children with developmental disabilities, including autism, often struggle to access services, information and resources in Argentina. Little is known about how caregivers can be empowered to support their children as they wish to in the Argentinian setting. We spoke with 32 people online to understand existing and potential practices of supporting caregivers. The people we spoke with included caregivers, health service providers, non-governmental organisations’ representatives providing services or technical support, special education teachers and policy representatives. Participants said that poverty, and inequalities in accessing support, impact how caregivers can support their children. They mentioned examples that help caregivers feel empowered, such as peer support groups and caregiver training. Many caregivers spoke about how they became advocates for their children and how they developed initiatives such as advocacy campaigns and well-being support groups. Caregivers in Argentina may be empowered in various ways, and the following strategies can improve empowerment: strengthening collaboration between professionals and caregivers; focusing on caregiver mental health; and addressing the profound impact of poverty on the quality of life of families.

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18. Watkins LV, Moon S, Burrows L, Tromans S, Barwell J, Shankar R. Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence. Expert Opin Pharmacother;2024 (Mar 18):1-13.

INTRODUCTION: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the FMR1 (fragile X messenger ribonucleoprotein 1) gene. The molecular understanding of the impact of the FMR1 gene mutation provides an opportunity to target treatment not only at symptoms but also on a molecular level. METHODS: We conducted a systematic review to provide an up-to-date narrative summary of the current evidence for pharmacological treatment in FXS. The review was restricted to randomized, blinded, placebo-controlled trials. RESULTS: The outcomes from these studies are discussed and the level of evidence assessed against validated criteria. The initial search identified 2377 articles, of which 16 were included in the final analysis. CONCLUSION: Based on this review to date there is limited data to support any specific pharmacological treatments, although the data for cannabinoids are encouraging in those with FXS and in future developments in gene therapy may provide the answer to the search for precision medicine. Treatment must be person-centered and consider the combination of medical, genetic, cognitive, and emotional challenges.

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19. Wegiel J, Chadman K, London E, Wisniewski T, Wegiel J. Contribution of the serotonergic system to developmental brain abnormalities in autism spectrum disorder. Autism Res;2024 (Mar 18)

This review highlights a key role of the serotonergic system in brain development and in distortions of normal brain development in early stages of fetal life resulting in cascades of abnormalities, including defects of neurogenesis, neuronal migration, neuronal growth, differentiation, and arborization, as well as defective neuronal circuit formation in the cortex, subcortical structures, brainstem, and cerebellum of autistic subjects. In autism, defects in regulation of neuronal growth are the most frequent and ubiquitous developmental changes associated with impaired neuron differentiation, smaller size, distorted shape, loss of spatial orientation, and distortion of cortex organization. Common developmental defects of the brain in autism include multiregional focal dysplastic changes contributing to local neuronal circuit distortion, epileptogenic activity, and epilepsy. There is a discrepancy between more than 500 reports demonstrating the contribution of the serotonergic system to autism’s behavioral anomalies, highlighted by lack of studies of autistic subjects’ brainstem raphe nuclei, the center of brain serotonergic innervation, and of the contribution of the serotonergic system to the diagnostic features of autism spectrum disorder (ASD). Discovery of severe fetal brainstem auditory system neuronal deficits and other anomalies leading to a spectrum of hearing deficits contributing to a cascade of behavioral alterations, including deficits of social and verbal communication in individuals with autism, is another argument to intensify postmortem studies of the type and topography of, and the severity of developmental defects in raphe nuclei and their contribution to abnormal brain development and to the broad spectrum of functional deficits and comorbid conditions in ASD.

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20. Wu J, Zhang J, Chen X, Wettschurack K, Que Z, Deming BA, Olivero-Acosta MI, Cui N, Eaton M, Zhao Y, Li SM, Suzuki M, Chen I, Xiao T, Halurkar MS, Mandal P, Yuan C, Xu R, Koss WA, Du D, Chen F, Wu LJ, Yang Y. Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids. Mol Psychiatry;2024 (Mar 18)

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

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21. Zhao W, Xu S, Zhang Y, Li D, Zhu C, Wang K. The Application of Extended Reality in Treating Children with Autism Spectrum Disorder. Neurosci Bull;2024 (Mar 18)

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder in children, characterized by social interaction, communication difficulties, and repetitive and stereotyped behaviors. Existing intervention methods have limitations, such as requiring long treatment periods and needing to be more convenient to implement. Extended Reality (XR) technology offers a virtual environment to enhance children’s social, communication, and self-regulation skills. This paper compares XR theoretical models, application examples, and intervention effects. The study reveals that XR intervention therapy is mainly based on cognitive rehabilitation, teaching, and social-emotional learning theories. It utilizes algorithms, models, artificial intelligence (AI), eye-tracking, and other technologies for interaction, achieving diverse intervention outcomes. Participants showed effective improvement in competency barriers using XR-based multimodal interactive platforms. However, Mixed Reality (MR) technology still requires further development. Future research should explore multimsodal interaction technologies combining XR and AI, optimize models, prioritize the development of MR intervention scenarios, and sustain an optimal intervention level.

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22. Zhou W, Sun M, Xu X, Ruan Y, Sun C, Li W, Gao X. Multipattern graph convolutional network-based autism spectrum disorder identification. Cereb Cortex;2024 (Mar 1);34(3)

The early diagnosis of autism spectrum disorder (ASD) has been extensively facilitated through the utilization of resting-state fMRI (rs-fMRI). With rs-fMRI, the functional brain network (FBN) has gained much attention in diagnosing ASD. As a promising strategy, graph convolutional networks (GCN) provide an attractive approach to simultaneously extract FBN features and facilitate ASD identification, thus replacing the manual feature extraction from FBN. Previous GCN studies primarily emphasized the exploration of topological simultaneously connection weights of the estimated FBNs while only focusing on the single connection pattern. However, this approach fails to exploit the potential complementary information offered by different connection patterns of FBNs, thereby inherently limiting the performance. To enhance the diagnostic performance, we propose a multipattern graph convolution network (MPGCN) that integrates multiple connection patterns to improve the accuracy of ASD diagnosis. As an initial endeavor, we endeavored to integrate information from multiple connection patterns by incorporating multiple graph convolution modules. The effectiveness of the MPGCN approach is evaluated by analyzing rs-fMRI scans from a cohort of 92 subjects sourced from the publicly accessible Autism Brain Imaging Data Exchange database. Notably, the experiment demonstrates that our model achieves an accuracy of 91.1% and an area under ROC curve score of 0.9742. The implementation codes are available at https://github.com/immutableJackz/MPGCN.

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