1. Westover AN. The Future of General Psychiatry Must Include Autism Spectrum Disorder and Intellectual Disability. Acad Psychiatry;2024 (May 23)

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2. Napoli SB, Vitale MP, Urinovsky MG, Fassero MP, Buján L, Molina JP, Rodríguez E, Schiariti V. Functional assessment of children and adolescents with autism spectrum disorder in Argentina: ICF-ASD multicenter study. Arch Argent Pediatr;2024 (May 30):e202310171.

Introduction. Autism spectrum disorder (ASD) is characterized by difficulties in social communication and repetitive and stereotyped behaviors. In addition to the diagnostic category, the activities performed by children and adolescents and their social involvement are the main aspects to be considered according to the International Classification of Functioning, Disability, and Health (ICF) proposed by the World Health Organization to describe health status. In a previous study, we developed the first version of a pediatric tool based on the ICF called ICF-ASD for the functional assessment of children and adolescents with ASD to capture functional characteristics adapted to our cultural setting. Our subsequent objective was to apply the ICF-ASD in a multicenter format to assess children and adolescents from different regions, review, and update it, and identify barriers and facilitators. Population and methods. The ICF-ASD version 1.0 was administered to children and adolescents younger than 16 years with a confirmed diagnosis of ASD (as per DSM-5 criteria), who were receiving follow-up at 5 children’s health centers across Argentina. Results. Version 2.0 of the ICF-ASD was obtained, which included 34 categories (10 under body function, 15 under activities and participation, and 9 under environmental factors). A functional profile was developed for the whole sample (n = 308). Conclusions. The updated version of the ICF-ASD helps to standardize and systematize the collection of necessary data for an adequate follow-up of children and adolescents with ASD at a national level. It also allows to identify barriers to overcome and facilitators to be generalized.

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3. Wilkinson KM, Brittlebank S, Barwise A, Zimmerman TO, Light J. Visual fixation patterns to AAC displays are significantly correlated with motor selection for individuals with Down syndrome or individuals on the autism spectrum. Augment Altern Commun;2024 (May 24):1-13.

Eye tracking research technologies are often used to study how individuals attend visually to different types of AAC displays (e.g. visual scene displays, grid displays). The assumption is that efficiency of visual search may relate to efficiency of motor selection necessary for communication via aided AAC; however, this assumption has not received direct empirical study. We examined the relation between speed of visual search and speed of motor selection of symbols. Ten individuals on the autism spectrum (AS; Study 1) and nine with Down syndrome (DS; Study 2) participated in a search task using simulated AAC displays with a main visual scene display (VSD) and a navigation bar of thumbnail VSDs. Participants were given an auditory prompt to find one of four thumbnail VSDs in the navigation bar. Eye tracking technologies measured how long it took participants to fixate visually on the thumbnail VSD, and recorded how long it took participants to select the thumbnail VSD with a finger. A statistically significant relationship emerged between visual fixation and selection latencies, confirming the positive relationship between visual processing and motor selection for both groups of participants. Eye tracking data may serve as a useful proxy measure for evaluating how display design influences selection of AAC symbols, especially when individuals are unwilling or unable to comply with traditional behaviorally-based assessment tasks.

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4. Hutchins TL, Knox SE, Fletcher EC. Natural language acquisition and gestalt language processing: A critical analysis of their application to autism and speech language therapy(). Autism Dev Lang Impair;2024 (Jan-Dec);9:23969415241249944.

BACKGROUND AND AIM: Recently, there has been a lot of interest surrounding the term gestalt language processor (GLP) which is associated with Natural Language Acquisition (NLA): a protocol intended to support the language development of autistic people. In NLA, delayed echolalia is presumed raw source material that GLPs use to acquire language in a stage-like progression from delayed echolalia to spontaneous speech. The aim of this article is to evaluate NLA in light of relevant literatures to allow scrutiny of NLA claims. MAIN CONTRIBUTIONS: First, we review the notion of gestalt language and situate it in the broader literature on language styles to update understanding of its significance. We then review the links from gestalt language processing to autism and identify definitional and conceptual problems and clarify the construct ‘episodic memory’. We discuss the ‘raw material view of delayed echolalia’ and identify theoretical and empirical shortcomings. Finally, we review Blanc’s language stages and their accompanying assessment and language support recommendations and challenge their validity. CONCLUSIONS & IMPLICATIONS: The term ‘gestalt language processor’ is definitionally and conceptually troubled, the assertion that autistic people are GLPs is misleading and unhelpful, and evidence is lacking that GLP represents a legitimate clinical entity. The theoretical basis of NLA lacks empirical support. NLA stages are implausible and their accompanying assessment and support recommendations lack justification. We recommend the use of alternate, individualized, theoretically-sound, evidence-based, neurodiversity-affirming supports that are sensitive and responsive to the heterogeneity that defines autism.

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5. Anderson JT, Roth JD, Rosenau KA, Dwyer PS, Kuo AA, Martinez-Agosto JA. Enhancing multi-site autism research through the development of a collaborative data platform. Autism Res;2024 (May 24)

Data repositories, particularly those storing data on vulnerable populations, increasingly need to carefully consider not only what data is being collected, but how it will be used. As such, the Autism Intervention Research Network on Physical Health (AIR-P) has created the Infrastructure for Collaborative Research (ICR) to establish standards on data collection practices in Autism repositories. The ICR will strive to encourage inter-site collaboration, amplify autistic voices, and widen accessibility to data. The ICR is staged as a three-tiered framework consisting of (1) a request for proposals system, (2) a REDCap-based data repository, and (3) public data dashboards to display aggregate de-identified data. Coupled with a review process including autistic and non-autistic researchers, this framework aims to propel the implementation of equitable autism research, enhance standardization within and between studies, and boost transparency and dissemination of findings. In addition, the inclusion of a contact registry that study participants can opt into creates the base for a robust participant pool. As such, researchers can leverage the platform to identify, reach, and distribute electronic materials to a greater proportion of potential participants who likely fall within their eligibility criteria. By incorporating practices that promote effective communication between researchers and participants, the ICR can facilitate research that is both considerate of and a benefit to autistic people.

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6. Davy G, Barbaro J, Unwin K, Clark M, Jellett R, Date P, Muniandy M, Dissanayake C. Child and caregiver predictors of primary caregiver participation in families of school-aged Autistic children. Autism Res;2024 (May 23)

Engaging in meaningful activities (e.g., leisure, spiritual, fitness) significantly affects caregivers’ quality of life (QoL), yet the determinants of participation in caregivers of Autistic children remain largely unknown. The current study examined child and caregiver correlates of primary caregiver participation in meaningful activities. One hundred and six primary caregivers of Autistic children (7-12 years) were recruited from three unique cohorts of Autistic children in this cross-sectional study. Primary caregivers completed online questionnaires measuring occupational gaps (i.e., desired activities caregivers are not participating in), QoL, parenting stress, perceived family outcomes, and social support. In addition to undertaking direct assessments of children’s cognition and language, primary caregivers also reported on their child’s adaptive behavior, social-emotional skills, and participation. Caregivers reporting fewer occupational gaps (i.e., ≤2 desired activities) were more likely to have Autistic children with no co-occurring conditions, who were older, and with better adaptive behaviors, social-emotional skills, and more frequent home and school participation, compared to caregivers reporting many gaps (i.e., ≥3 desired activities). Caregivers with fewer occupational gaps also reported improved QoL, parenting stress, social support, perceived community inclusiveness, and family outcomes. Logistic regression analysis identified child age, child adaptive behavior, social-emotional skills, home participation, and the caregivers’ perceived family outcomes and QoL as important predictors of their occupational gaps. The findings demonstrate that caregiver participation in desired activities was associated with increased functional ability and independence of the child, as well as their perceived capacity to meet their child’s needs. Supporting parents’ sense of efficacy in meeting their children’s needs and building their skills and knowledge will serve to improve both caregiver and child outcomes.

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7. Thiel T, Riedelbauch S, Gaigg S, Roessner V, Ring M. The impact of depressive and anxious symptoms on quality of life in adults on the autism spectrum. Autism Res;2024 (May 24)

Quality of life (QoL) is lower in adults on the autism spectrum (AS) compared with typically developing (TD) adults. In this context, recent studies have examined the role of depression and anxiety in reducing QoL in AS adults. The aim of this study was to (1) replicate these findings of lower QoL and (2) assess the negative influence of depressive and anxious symptoms on QoL in an adult AS (N = 86) and TD (N = 87) German sample with a broad age range (18-70 years). For this, we used questionnaires that have been validated for the AS and TD population: the World Health Organization Quality of Life Brief Version, the Autism-Specific QoL items, and the Hospital Anxiety and Depression Scale. We replicated previous findings and extended them to autism-specific QoL. Our AS sample had lower QoL compared with the TD adults. However, depressive symptoms were the largest contributor to lower QoL in both samples, more so than group membership and anxious symptoms. We conclude that interventions to improve QoL in AS adults should specifically target depressive symptoms and for this, improvements to the diagnostic process and treatment of depression in AS are necessary.

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8. Liu C, Guo Z, Pang J, Zhang Y, Yang Z, Cao J, Zhang T. Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism. Behav Brain Res;2024 (May 22);469:115052.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat’s model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

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9. Yu L, Liu Y, Xia J, Feng S, Chen F. KCNH5 deletion increases autism susceptibility by regulating neuronal growth through Akt/mTOR signaling pathway. Behav Brain Res;2024 (May 24):115069.

Recent clinical studies have highlighted mutations in the voltage-gated potassium channel Kv10.2 encoded by the KCNH5 gene among individuals with autism spectrum disorder (ASD). Our preliminary study found that Kv10.2 was decreased in the hippocampus of valproic acid (VPA) – induced ASD rats. Nevertheless, it is currently unclear how KCNH5 regulates autism-like features, or becomes a new target for autism treatment. We employed KCNH5 knockout (KCNH5(-/-)) rats and VPA – induced ASD rats in this study. Then, we used behavioral assessments, combined with electrophysiological recordings and hippocampal brain slice, to elucidate the impact of KCNH5 deletion and environmental factors on neural development and function in rats. We found that KCNH5(-/-) rats showed early developmental delay, neuronal overdevelopment, and abnormal electroencephalogram (EEG) signals, but did not exhibit autism-like behavior. KCNH5(-/-) rats exposed to VPA (KCNH5(-/-)-VPA) exhibit even more severe autism-like behaviors and abnormal neuronal development. The absence of KCNH5 excessively enhances the activity of the Protein Kinase B (Akt)/Mechanistic Target of Rapamycin (mTOR) signaling pathway in the hippocampus of rats after exposure to VPA. Overall, our findings underscore the deficiency of KCNH5 increases the susceptibility to autism under environmental exposures, suggesting its potential utility as a target for screening and diagnosis in ASD.

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10. López Resa P, Moraleda Sepúlveda E. Developmental Profile in Children Aged 3-6 Years: Down Syndrome vs. Autism Spectrum Disorder. Behav Sci (Basel);2024 (Apr 30);14(5)

This research aims to compare the developmental profiles of children with autism spectrum disorder (ASD) and children with Down Syndrome (DS) between the ages of 3 and 6 years. The study examines whether these developmental disorders share common developmental milestones or exhibit distinctive characteristics. A total of 43 children, 23 with DS and 20 with ASD, participated in the study. Cognitive and language skills were assessed using standardized tools, including the Battelle Developmental Inventory, Reynell Developmental Language Scales III, and NEPSY-II battery. The results indicated that children with ASD outperformed children with DS in the areas of fine motor skills, gross motor skills, and communication. Additionally, children with ASD demonstrated higher scores in language comprehension and expressive language, compared to children with DS. Significant correlations were found between motor skills and communication abilities. Neuropsychological evaluations revealed significant differences between the two groups in various tasks, such as the comprehension of instructions, body part naming and identification, and recognition of emotions. These findings contribute to our understanding of the similarities and differences between ASD and DS, shedding light on the dissociation between cognition and language and its impact on adaptive functioning in these populations.

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11. Yasin M, Licchetta L, Khan N, Ullah I, Jan Z, Dawood M, Ahmed AN, Azeem A, Minardi R, Carelli V, Saleha S. Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families. BMC Neurol;2024 (May 23);24(1):172.

BACKGROUND: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. METHODS: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. RESULTS: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. CONCLUSION: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

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12. Martinez JD, Wilson LG, Brancaleone WP, Peterson KG, Popke DS, Garzon VC, Perez Tremble RE, Donnelly MJ, Mendez Ortega SL, Torres D, Shaver JJ, Jiang S, Yang Z, Aton SJ. Hypnotic treatment improves sleep architecture and EEG disruptions and rescues memory deficits in a mouse model of fragile X syndrome. Cell Rep;2024 (May 23);43(6):114266.

Fragile X syndrome (FXS) is associated with disrupted cognition and sleep abnormalities. Sleep loss negatively impacts cognitive function, and one untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We tested whether ML297, a hypnotic acting on G-protein-activated inward-rectifying potassium (GIRK) channels, could reverse sleep phenotypes and disrupted memory in Fmr1(-/y) mice. Fmr1(-/y) mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM architecture, altered sleep electroencephalogram (EEG) oscillations, and reduced EEG coherence between cortical areas; these are partially reversed following ML297 administration. Treatment following contextual fear or spatial learning restores disrupted memory consolidation in Fmr1(-/y) mice. During memory recall, Fmr1(-/y) mice show an altered balance of activity among hippocampal principal neurons vs. parvalbumin-expressing interneurons; this is partially reversed by ML297. Because sleep disruption could impact neurophysiological phenotypes in FXS, augmenting sleep may improve disrupted cognition in this disorder.

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13. Lencastre P, Lotfigolian M, Lind PG. Identifying Autism Gaze Patterns in Five-Second Data Records. Diagnostics (Basel);2024 (May 18);14(10)

One of the most challenging problems when diagnosing autism spectrum disorder (ASD) is the need for long sets of data. Collecting data during such long periods is challenging, particularly when dealing with children. This challenge motivates the investigation of possible classifiers of ASD that do not need such long data sets. In this paper, we use eye-tracking data sets covering only 5 s and introduce one metric able to distinguish between ASD and typically developed (TD) gaze patterns based on such short time-series and compare it with two benchmarks, one using the traditional eye-tracking metrics and one state-of-the-art AI classifier. Although the data can only track possible disorders in visual attention and our approach is not a substitute to medical diagnosis, we find that our newly introduced metric can achieve an accuracy of 93% in classifying eye gaze trajectories from children with ASD surpassing both benchmarks while needing fewer data. The classification accuracy of our method, using a 5 s data series, performs better than the standard metrics in eye-tracking and is at the level of the best AI benchmarks, even when these are trained with longer time series. We also discuss the advantages and limitations of our method in comparison with the state of the art: besides needing a low amount of data, this method is a simple, understandable, and straightforward criterion to apply, which often contrasts with « black box » AI methods.

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14. Medeiros D, Ayala-Baylon K, Egido-Betancourt H, Miller E, Chapleau C, Robinson H, Phillips ML, Yang T, Longo FM, Li W, Pozzo-Miller L. A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice. Dis Model Mech;2024 (Jun 1);17(6)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, which encodes methyl-CpG-binding protein 2, a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of LM22A-4, a brain-penetrant, small-molecule ligand of the BDNF receptor TrkB (encoded by Ntrk2), on dendritic spine density and form in hippocampal pyramidal neurons and on behavioral phenotypes in female Mecp2 heterozygous (HET) mice. A 4-week systemic treatment of Mecp2 HET mice with LM22A-4 restored spine volume in MeCP2-expressing neurons to wild-type (WT) levels, whereas spine volume in MeCP2-lacking neurons remained comparable to that in neurons from female WT mice. Female Mecp2 HET mice engaged in aggressive behaviors more than WT mice, the levels of which were reduced to WT levels by the 4-week LM22A-4 treatment. These data provide additional support to the potential usefulness of novel therapies not only for RTT but also to other BDNF-related disorders.

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15. Li L, Jia S, Wang P, Li S, Wang X, Zhu X. A network meta-analysis of the effect of physical exercise on core symptoms in patients with autism spectrum disorders. Front Neurol;2024;15:1360434.

OBJECTIVE: To compare the effects of various sports exercise programs on the core symptoms of patients with autism spectrum disorder (ASD). METHODS: We searched the China National Knowledge Infrastructure, VIP databases, Wanfang databases, Cochrane Library, PubMed, EMBASE, and Web of Science databases from their inception to February 2023 for randomized controlled trial that investigated the effect of sports exercise on the core symptoms of ASD. The overall risk of bias in the included literature was summarized using the revised Cochrane Randomized Trial Risk of Bias Tool (ROB2), and network meta-analysis was used to compare the intervention effects. RESULTS: A total of 30 studies involving 1,375 participants were included. The results showed that sports exercise programs, including 8-12 weeks of ball sports (SMD = -5.35, 95%CI: -7.57, -3.23), horse riding (SMD = -3.71, 95%CI: -6.18, -1.13), 8-12 weeks of comprehensive sports exercise (SMD = -2.17, 95%CI: -3.99, -0.44), and more than 12 weeks of comprehensive sports exercise (SMD = -3.75, 95%CI: -6.33, -1.24), significantly improved social interaction disorders. Furthermore, 8-12 weeks of ball sports (SMD = -4.36, 95%CI: 2.04, 6.73) and more than 12 weeks of comprehensive sports exercise (SMD = 3.65, 95%CI: 1.40, 6.08) significantly improved repetitive behaviors and restricted interests. CONCLUSION: Sports exercise can improve the core symptoms of ASD patients, and different symptoms show a selective response to different exercise elements. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42023455806.

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16. Shrader SH, Mellen N, Cai J, Barnes GN, Song ZH. Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism. Front Neurosci;2024;18:1359810.

INTRODUCTION: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified. Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T(+)Itpr3(tf)/J (BTBR) mice, an established mouse model of idiopathic ASD. METHODS: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice. RESULTS: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment. DISCUSSION: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.

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17. Li Y, Xiao P, Cao R, Le J, Xu Q, Xiao F, Ye L, Wang X, Wang Y, Zhang T. Effects and microbiota changes following oral lyophilized fecal microbiota transplantation in children with autism spectrum disorder. Front Pediatr;2024;12:1369823.

BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders that is characterized by core features in social communication impairment and restricted, repetitive sensory-motor behaviors. This study aimed to further investigate the utilization of fecal microbiota transplantation (FMT) in children with ASD, both with and without gastrointestinal (GI) symptoms, evaluate the effect of FMT and analyze the alterations in bacterial and fungal composition within the gut microbiota. METHODS: A total of 38 children diagnosed with ASD participated in the study and underwent oral lyophilized FMT treatment. The dosage of the FMT treatment was determined based on a ratio of 1 g of donor stool per 1 kg of recipient body weight, with a frequency of once every 4 weeks for a total of 12 weeks. In addition, 30 healthy controls (HC) were included in the analysis. The clinical efficacy of FMT was evaluated, while the composition of fecal bacteria and fungi was determined using 16S rRNA and ITS gene sequencing methods. RESULTS: Median age of the 38 children with ASD was 7 years. Among these children, 84.2% (32 of 38) were boys and 81.6% (31 of 38) exhibited GI symptoms, with indigestion, constipation and diarrhea being the most common symptoms. Sample collections and assessments were conducted at baseline (week 0), post-treatment (week 12) and follow-up (week 20). At the end of the follow-up phase after FMT treatment, the autism behavior checklist (ABC) scores decreased by 23% from baseline, and there was a 10% reduction in scores on the childhood autism rating scale (CARS), a 6% reduction in scores on the social responsiveness scale (SRS) and a 10% reduction in scores on the sleep disturbance scale for children (SDSC). In addition, short-term adverse events observed included vomiting and fever in 2 participants, which were self-limiting and resolved within 24 h, and no long-term adverse events were observed. Although there was no significant difference in alpha and beta diversity in children with ASD before and after FMT therapy, the FMT treatment resulted in alterations in the relative abundances of various bacterial and fungal genera in the samples of ASD patients. Comparisons between children with ASD and healthy controls (HC) revealed statistically significant differences in microbial abundance before and after FMT. Blautia, Sellimonas, Saccharomycopsis and Cystobasidium were more abundant in children with ASD than in HC, while Dorea were less abundant. After FMT treatment, levels of Blautia, Sellimonas, Saccharomycopsis and Cystobasidium decreased, while levels of Dorea increased. Moreover, the increased abundances of Fusicatenibacter, Erysipelotrichaceae_UCG-003, Saccharomyces, Rhodotorula, Cutaneotrichosporon and Zygosaccharomyces were negatively correlated with the scores of ASD core symptoms. CONCLUSIONS: Oral lyophilized FMT could improve GI and ASD related symptoms, as well as sleep disturbances, and alter the gut bacterial and fungal microbiota composition in children with ASD. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, www.chictr.org.cn.

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18. Wang M, Jeon M. Assistive technology for adults on the autism spectrum: A systematic survey. Int J Hum Comput Interact;2024;40(10):2433-2452.

While the needs and care for children on the autism spectrum have been widely investigated, the intervention and services available to autistic adults have been overlooked for a long time. This survey paper reviewed 32 articles that described and evaluated assistive technologies that have been developed and evaluated through a complete circle of interactive product design from ideation, prototype, and user evaluation. These assistive technologies aim to improve independence and living quality in autistic adults. We extracted information from the perspective of requirement gathering, technology designing, and effectiveness of evaluation in the design cycle. We found a general lack of requirements-driven design, and the evaluation process was not standardized either. The lack of requirement gathering results in designs purely based on existing literature without targeting actual user needs. Our synthesis of included paper contributes to developing iterative design considerations in assistive technologies for autistic adults. We also suggest that assistive technologies for autistic adults shift some attention from assisting only autistic adults who require at least substantial support to embracing also those who have been living independently but rather have difficulties in social interaction. Assistive technologies for them have the potentials to help them consolidate and enhance their experiences in independent living.

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19. Izuno-Garcia AK, Vanderburg JL, Pagán AF, Loveland KA. Brief Report: Self-Reported Medication Use in Individuals Diagnosed with Autism Spectrum Disorder in Adulthood: A U.S. Clinic Sample from 2012 to 2022. J Autism Dev Disord;2024 (May 23)

PURPOSE: As the understanding of autism spectrum disorder (ASD) across the lifespan has increased, so has the number of individuals being identified with ASD for the first time in adulthood. Understanding co-occurring psychiatric conditions in this subset of the ASD population is a growing focus of research; however, little is known about the rate at which psychiatric medications are prescribed to adults with a first-time diagnosis of ASD. The purpose of this study was to examine self-reported medication use in persons diagnosed with ASD in adulthood in a clinic sample (2012-2022) in the United States. METHODS: The present study was a retrospective record review. Participants (n = 281) were drawn from an outpatient clinic specializing in the diagnosis of ASD in adults. Participants self-reported previous and current psychiatric medication prescription using a medication checklist. RESULTS: Approximately 50% of participants self-reported being prescribed at least one psychiatric medication at the time of their initial evaluation appointment. The most commonly prescribed psychiatric medications were antidepressants (23.8%), followed by stimulants (16.7%). CONCLUSION: Similar to individuals diagnosed with ASD in childhood, those identified with ASD for the first time in adulthood are prescribed psychiatric medication at a much higher rate than their same-age non-autistic peers. These results can inform future research and practice for improving outcomes for autistic adults, particularly those who were undiagnosed for much of their lives.

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20. Cabana-Domínguez J, Bosch R, Soler Artigas M, Alemany S, Llonga N, Vilar-Ribó L, Carabí-Gassol P, Arribas L, Macias-Chimborazo V, Español-Martín G, Del Castillo C, Martínez L, Pagerols M, Pagespetit È, Prat R, Puigbó J, Ramos-Quiroga JA, Casas M, Ribasés M. Dissecting the polygenic contribution of attention-deficit/hyperactivity disorder and autism spectrum disorder on school performance by their relationship with educational attainment. Mol Psychiatry;2024 (May 23)

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are strongly associated with educational attainment (EA), but little is known about their genetic relationship with school performance and whether these links are explained, in part, by the genetic liability of EA. Here, we aim to dissect the polygenic contribution of ADHD and ASD to school performance, early manifestation of psychopathology and other psychiatric disorders and related traits by their relationship with EA. To do so, we tested the association of polygenic scores for EA, ADHD and ASD with school performance, assessed whether the contribution of the genetic liability of ADHD and ASD to school performance is influenced by the genetic liability of EA, and evaluated the role of EA in the genetic overlap between ADHD and ASD with early manifestation of psychopathology and other psychiatric disorders and related traits in a sample of 4,278 school-age children. The genetic liability for ADHD and ASD dissected by their relationship with EA show differences in their association with school performance and early manifestation of psychopathology, partly mediated by ADHD and ASD symptoms. Genetic variation with concordant effects in ASD and EA contributes to better school performance, while the genetic variation with discordant effects in ADHD or ASD and EA is associated with poor school performance and higher rates of emotional and behavioral problems. Our results strongly support the usage of the genetic load for EA to dissect the genetic and phenotypic heterogeneity of ADHD and ASD, which could help to fill the gap of knowledge of mechanisms underlying educational outcomes.

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21. Rants S, Bradish K, Conlin H, Crandall N, Kirby N, Williams RM. PEERS® Curriculum for Children with Autism Spectrum Disorder: A Scoping Review. Phys Occup Ther Pediatr;2024 (May 23):1-9.

AIMS: The Program for the Education and Enrichment of Relational Skills (PEERS®), designed to enhance social skills and relationships for individuals with autism spectrum disorder (ASD) and their caregivers, has primarily been implemented with older children and adolescents ages 11-19, leaving a gap in research on its effectiveness in young children. This scoping review assesses evidence of the effectiveness of the PEERS® program for children with ASD. METHODS: A literature search was conducted, resulting in 97 articles. Following the implementation of inclusion and exclusion criteria, four articles of Level III and IV evidence based on CEBM guidelines were included in this review. RESULTS: All studies demonstrated positive findings regarding social skills development with one study revealing statistically significant results in increasing social skills and decreasing problem behaviors after participation in the PEERS® program. CONCLUSIONS: This scoping review found improvements in the PEERS® programs for social skills in young children (ages 4-7) with ASD. However, further research is warranted, emphasizing larger sample sizes, consideration of external factors, and implementation of randomization and blinding in future studies.

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22. Tost A, Romero S, Alonso JF, Bachiller A, Serna LY, Medina-Rivera I, García-Cazorla Á, Mañanas M. EEG connectivity patterns in response to gaming and learning-based cognitive stimulations in Rett syndrome. Res Dev Disabil;2024 (May 24);150:104751.

BACKGROUND: Functional connectivity is scarcely studied in Rett syndrome (RTT). Explorations revealed associations between RTT’s clinical, genetic profiles, and coherence measures, highlighting an unexplored frontier in understanding RTT’s neural mechanisms and cognitive processes. AIMS: To evaluate the effects of diverse cognitive stimulations-learning-focused versus gaming-oriented-on electroencephalography brain connectivity in RTT. The comparison with resting states aimed to uncover potential biomarkers and insights into the neural processes associated with RTT. METHODS AND PROCEDURES: The study included 15 girls diagnosed with RTT. Throughout sessions lasting about 25 min, participants alternated between active and passive tasks, using an eyetracker device while their brain activity was recorded with a 20-channel EEG. Results revealed significant alterations during cognitive tasks, notably in delta, alpha and beta bands. Both tasks induced spectral pattern changes and connectivity shifts, hinting at enhanced neural processing. Hemispheric asymmetry decreased during tasks, suggesting more balanced neural processing. Linear and nonlinear connectivity alterations were observed in active tasks compared to resting state, while passive tasks showed no significant changes. CONCLUSIONS AND IMPLICATIONS: Results underscores the potential of cognitive stimulation for heightened cognitive abilities, promoting enhanced brain connectivity and information flow in Rett syndrome. These findings offer valuable markers for evaluating cognitive interventions and suggest gaming-related activities as effective tools for improving learning outcomes.

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23. Yap CX, Vo DD, Heffel MG, Bhattacharya A, Wen C, Yang Y, Kemper KE, Zeng J, Zheng Z, Zhu Z, Hannon E, Vellame DS, Franklin A, Caggiano C, Wamsley B, Geschwind DH, Zaitlen N, Gusev A, Pasaniuc B, Mill J, Luo C, Gandal MJ. Brain cell-type shifts in Alzheimer’s disease, autism, and schizophrenia interrogated using methylomics and genetics. Sci Adv;2024 (May 24);10(21):eadn7655.

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer’s disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer’s disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial cell loss contributes to Alzheimer’s disease, with comparable effect size to APOE genotype among older people. Genome-wide association identified five genetic loci related to cell-type composition, involving plausible genes for the neurovascular unit (P2RX5 and TRPV3) and excitatory neurons (DPY30 and MEMO1). These results implicate specific cell-type shifts in the pathophysiology of neuropsychiatric disorders.

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24. Fajardo-Martinez V, Ferreira F, Fuller T, Cambou MC, Kerin T, Paiola S, Mok T, Rao R, Mohole J, Paravastu R, Zhang D, Marschik P, Iyer S, Kesavan K, Borges Lopes MDC, Britto JAA, Moreira ME, Brasil P, Nielsen-Saines K. Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero. Sci Rep;2024 (May 24);14(1):11851.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

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25. Wamsley B, Bicks L, Cheng Y, Kawaguchi R, Quintero D, Margolis M, Grundman J, Liu J, Xiao S, Hawken N, Mazariegos S, Geschwind DH. Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics. Science;2024 (May 24);384(6698):eadh2602.

Genomic profiling in postmortem brain from autistic individuals has consistently revealed convergent molecular changes. What drives these changes and how they relate to genetic susceptibility in this complex condition are not well understood. We performed deep single-nucleus RNA sequencing (snRNA-seq) to examine cell composition and transcriptomics, identifying dysregulation of cell type-specific gene regulatory networks (GRNs) in autism spectrum disorder (ASD), which we corroborated using single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) and spatial transcriptomics. Transcriptomic changes were primarily cell type specific, involving multiple cell types, most prominently interhemispheric and callosal-projecting neurons, interneurons within superficial laminae, and distinct glial reactive states involving oligodendrocytes, microglia, and astrocytes. Autism-associated GRN drivers and their targets were enriched in rare and common genetic risk variants, connecting autism genetic susceptibility and cellular and circuit alterations in the human brain.

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26. Wen C, Margolis M, Dai R, Zhang P, Przytycki PF, Vo DD, Bhattacharya A, Matoba N, Tang M, Jiao C, Kim M, Tsai E, Hoh C, Aygün N, Walker RL, Chatzinakos C, Clarke D, Pratt H, Peters MA, Gerstein M, Daskalakis NP, Weng Z, Jaffe AE, Kleinman JE, Hyde TM, Weinberger DR, Bray NJ, Sestan N, Geschwind DH, Roeder K, Gusev A, Pasaniuc B, Stein JL, Love MI, Pollard KS, Liu C, Gandal MJ. Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain. Science;2024 (May 24);384(6698):eadh0829.

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.

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27. Feng YR, Zhang Q, Miao JK, Yang T, Chen J, Chen HY, Mou QH, Xiang XL, Long D, Wei QH, Wu Y, Li TY. Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder. World J Pediatr;2024 (May 24)

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

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