1. Zajic MC, Gudknecht J. Person- and identity-first language in autism research: A systematic analysis of abstracts from 11 autism journals. Autism. 2024: 13623613241241202.

There are many ways to refer to an individual who is on the autism spectrum. A recommended approach has been to use person-first language (PFL), such as « person with autism. » A different approach is to use identity-first language (IFL), such as « autistic person. » Recent studies focused on different groups of people (e.g. autistic self-advocates, parents, and practitioners) show that some groups prefer PFL (practitioners) while others prefer IFL (autistic self-advocates). However, less is known about how researchers use PFL and IFL in academic writing (e.g. studies published in scientific journals) involving autistic research participants. Our study examined 12,962 journal abstracts (short summaries of scientific articles) from 11 academic journals that publish autism research findings. We wanted to know (a) about the use of PFL and IFL across abstracts, and (b) how PFL and IFL use has changed annually over time. We examined data for all journals individually and grouped together. Our findings showed that journal abstracts generally use PFL (65%) with some using either IFL (16%) or both PFL and IFL (20%). However, journals varied, with some showing a clear majority for PFL and a couple for IFL. Examining trends over time across journals showed that while PFL appeared to be the majority for most journals, IFL has steadily increased in the recent few years. Our study helps us understand how autism researchers write about autistic individuals and offers implications for helping researchers intentionally make choices about the language used in their autism research studies.

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2. İnci S, Nisticò V, Folatti I, Santangelo G, Sanguineti C, Faggioli R, Bertani A, Gambini O, Demartini B. Autistic Traits Among Adolescents and Young Adults Under Assessment for Psychiatric Conditions: An Experimental Analysis of Prevalence – CORRIGENDUM. BJPsych Open. 2024; 10(3): e72.

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3. Meneses Castaño CY, Penagos P. Transcranial Magnetic Stimulation in the Treatment of Autism Spectrum Disorder: An Approach. Curr Pediatr Rev. 2024.

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4. Jertberg RM, Begeer S, Geurts HM, Chakrabarti B, Van der Burg E. Age, not autism, influences multisensory integration of speech stimuli among adults in a McGurk/MacDonald paradigm. Eur J Neurosci. 2024.

Differences between autistic and non-autistic individuals in perception of the temporal relationships between sights and sounds are theorized to underlie difficulties in integrating relevant sensory information. These, in turn, are thought to contribute to problems with speech perception and higher level social behaviour. However, the literature establishing this connection often involves limited sample sizes and focuses almost entirely on children. To determine whether these differences persist into adulthood, we compared 496 autistic and 373 non-autistic adults (aged 17 to 75 years). Participants completed an online version of the McGurk/MacDonald paradigm, a multisensory illusion indicative of the ability to integrate audiovisual speech stimuli. Audiovisual asynchrony was manipulated, and participants responded both to the syllable they perceived (revealing their susceptibility to the illusion) and to whether or not the audio and video were synchronized (allowing insight into temporal processing). In contrast with prior research with smaller, younger samples, we detected no evidence of impaired temporal or multisensory processing in autistic adults. Instead, we found that in both groups, multisensory integration correlated strongly with age. This contradicts prior presumptions that differences in multisensory perception persist and even increase in magnitude over the lifespan of autistic individuals. It also suggests that the compensatory role multisensory integration may play as the individual senses decline with age is intact. These findings challenge existing theories and provide an optimistic perspective on autistic development. They also underline the importance of expanding autism research to better reflect the age range of the autistic population.

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5. Brito F, Lagos C, Cubillos J, Orellana J, Gajardo M, Böhme D, Encina G, Repetto GM. Genomic analysis in Chilean patients with suspected Rett syndrome: keep a broad differential diagnosis. Front Genet. 2024; 15: 1278198.

Introduction: Rett syndrome (RTT, MIM #312750) is a rare genetic disorder that leads to developmental regression and severe disability and is caused by pathogenic variants in the MECP2 gene. The diagnosis of RTT is based on clinical features and, depending on resources and access, on molecular confirmation. There is scarce information on molecular diagnosis from patients in Latin America, mostly due to limited availability and coverage of genomic testing. This pilot study aimed to implement genomic testing and characterize clinical and molecular findings in a group of Chilean patients with a clinical diagnosis of RTT. Methods: Twenty-eight patients with suspected RTT underwent characterization of phenotypic manifestations and molecular testing using Clinical Exome Solution(TM) CES_V2 by SOPHiA Genetics. Data was analyzed using the commercial bioinformatics platform, SOPHiA DDM(TM). A virtual panel of 34 genes, including MECP2 and other genes that are in the differential diagnosis of RTT, was used to prioritize initial analyses, followed by evaluation of the complete exome sequence data. Results: Twelve patients (42.8% of participants) had variants in MECP2, of which 11 (39.2%) were interpreted as pathogenic/likely pathogenic (P/LP), thus confirming the diagnosis of RTT in them. Eight additional patients (28.5%) harbored ten variants in nine other genes. Four of these variants were interpreted as P/LP (14.2%) (GRIN2B, MADD, TRPM3 and ZEB2) resulting in alternative neurodevelopmental diagnoses, and six were considered of uncertain significance. No evident candidate variant was found for eight patients. Discussion: This study allowed to reach a diagnosis in half of the participants. The diagnosis of RTT was confirmed in over a third of them, while others were found to have alternative neurodevelopmental disorders. Further evaluation is needed to identify the cause in those with negative or uncertain results. This information is useful for the patients, families, and clinicians to guide clinical management, even more so since the development of novel therapies for RTT. We also show the feasibility of implementing a step-wide approach to genomic testing in a setting with limited resources.

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6. Homayounnia Firouzjah M, Majidi Yaeichi N, Hematinia R. The Effectiveness of Sensory-Motor Integration Exercises on Social Skills and Motor Performance in Children with Autism. J Autism Dev Disord. 2024.

PURPOSE: The current study aims to investigate the effectiveness of sensory-motor integration exercises on social skills and motor performance in children with autism spectrum disorder (ASD). METHODS: This is a quasi-experimental study with a pre-test-post-test design and with a control group. The statistical population of this research included all children with ASD aged 9-11 years old in Babolsar city in 2022, among whom 30 were selected through convenient sampling from the transplant center of Babolsar, and were randomly assigned into two experimental and control groups. Then, the experimental group received the treatment program in 12 sessions. The data collection instrument included Gresham and Elliott’s social skills questionnaire (Gresham FM, Elliott SN (1993) Social skills intervention guide: systematic approaches to social skills training. Spec Serv Sch 8(1):137-158) and Ulrich’s motor performance test (Ulrich B, Ulrich D (1985) The role of balancing ability in performance of fundamental motor skills in 3-, 4-, and 5-year-old children. Motor Dev: Curr Select Res 1:87-97). Data analysis was conducted using covariance analysis in SPSS21. RESULTS: The multivariate covariance analysis test showed that there is a significant difference between the experimental and control groups in the variable of social skills and motor performance, respectively (P < 0.001). CONCLUSION: According to the research findings, it can be concluded that sensory-motor integration exercises can be used as an appropriate intervention in promoting and improving social skills and motor performance of children with autism spectrum. Results of this study can be helpful for therapists and educators who deal with autistic children.

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7. MacFarland MC, Plavnick JB, Kipfmiller KJ, McElyea AS. Using Video Modeling to Teach Neurotypical Adolescents to Interact Socially with Peers with ASD. J Autism Dev Disord. 2024.

Research has shown video modeling to be effective for training adult service providers to administer evidence-based practices to children with autism. This study examined the effects of video modeling training (VMT) on neurotypical adolescents’ performance of peer mediated social interaction (PMSI), a 10-step procedure of simplified behavioral practices, during roleplay with an adult actor. A multiple probe design across participants evaluated the effects of VMT on delivery of PMSI by five neurotypical adolescents. All participants demonstrated immediate increases and generalized delivery of PMSI to four adolescents with autism following VMT. Social interaction for two additional youths with autism also improved when evaluated within a peer mediated setting, as a measure of social validity, before and after VMT.

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8. Shapter S, Carroll A, Roberts K. Clinician Opinions Regarding the Usefulness of the BOSA for ASD Assessment in a Service for Children Aged Under 12 Years. J Autism Dev Disord. 2024.

The COVID-19 pandemic and the subsequent social distancing policies forced healthcare teams to drastically alter the way they deliver services. This was particularly challenging for clinicians involved in diagnosing autism spectrum disorder (ASD), as assessment tools and methods required face-to-face social interactions between clinicians and children. To address this, the Brief Observation of Symptoms of Autism (BOSA) was developed to ensure that people suspected of ASD can receive diagnostic assessments during the pandemic. This project aimed to explore clinicians’ opinions on the BOSA, particularly regarding the usefulness of the assessment for clinicians to clarify diagnostic outcomes of ASD assessments. Both quantitative and qualitative data was gathered within an NHS community paediatric team. This included a questionnaire for clinicians to complete, and data from the BOSA assessments done in the service. Thematic analysis and descriptive statistics revealed that many clinicians felt that the BOSA can be beneficial in certain cases, such as selective mutism, and found the BOSA particularly helpful for observing parent-child interactions. These findings highlighted important information that the Autism Diagnostic Observation Schedule Second Edition (ADOS-2) does not give opportunities to observe. Clinicians reported that at times, the BOSA materials, brevity and parental administration created barriers to gathering information for diagnostic decisions. As may be expected, clinicians showed a clear preference for the more familiar and validated ADOS-2. However, the study highlights perceived limitations of the ADOS-2 and strengths of the BOSA, with recommendations made for future practice and research.

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9. Zatz JC, Harrison JR. K-12 Life Skills Education, Independence, and Employment of Autistic Individuals: Giving Voice to Autistic Adults. J Autism Dev Disord. 2024.

Autistic adults are often challenged to engage in and complete life skill tasks independently and are underrepresented in employment. No prior study has explored the perceptions of autistic individuals regarding K-12 life skills experiences and postsecondary employment. As such, the purposes of this study were to explore the association between components of life skills instruction and employment for 12 autistic individuals, and to elicit the perspectives of and experiences in K-12 education and employment of six autistic adults. As this was a mixed methods study, surveys and semi-structured interviews were conducted. Results of Fisher’s test indicated no statistically significant associations between employment and instructional components; however, the associations between employment and household chores [Cramer’s V = .60]; cooking [Cramer’s V = .66]; one-on-one instruction [Cramer’s V = .63]; and field trips [Cramer’s V = .41]) were large. The associations between employment and job site training [Cramer’s V = .33] and token boards [Cramer’s V = .33]) were moderate. Three themes and 10 subthemes emerged. Specifically, participants remembered Memorable Components from K-12 instruction: (a) job site training, (b) field trips, and (c) household chores. Participants perceived Beneficial Practices as: (a) job site training and (b) skills learned. Participants described shortcomings of K-12 instruction as need (a) for more skills training, (c) for social skills training, (d) to eliminate unnecessary instruction and (e) to carefully consider student placement. In conclusion, participants described experiences that helped them gain and attain post-secondary employment. More specific individualized programming in K-12 instruction would be beneficial to develop independence and post-secondary employment.

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10. Deehan MA, Kothuis JM, Sapp E, Chase K, Ke Y, Seeley C, Iuliano M, Kim E, Kennington L, Miller R, Boudi A, Shing K, Li X, Pfister E, Anaclet C, Brodsky M, Kegel-Gleason K, Aronin N, DiFiglia M. Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction. J Neurosci. 2024; 44(14).

A missense mutation in the transcription repressor Nucleus accumbens-associated 1 (NACC1) gene at c.892C>T (p.Arg298Trp) on chromosome 19 causes severe neurodevelopmental delay ( Schoch et al., 2017). To model this disorder, we engineered the first mouse model with the homologous mutation (Nacc1(+/R284W) ) and examined mice from E17.5 to 8 months. Both genders had delayed weight gain, epileptiform discharges and altered power spectral distribution in cortical electroencephalogram, behavioral seizures, and marked hindlimb clasping; females displayed thigmotaxis in an open field. In the cortex, NACC1 long isoform, which harbors the mutation, increased from 3 to 6 months, whereas the short isoform, which is not present in humans and lacks aaR284 in mice, rose steadily from postnatal day (P) 7. Nuclear NACC1 immunoreactivity increased in cortical pyramidal neurons and parvalbumin containing interneurons but not in nuclei of astrocytes or oligodendroglia. Glial fibrillary acidic protein staining in astrocytic processes was diminished. RNA-seq of P14 mutant mice cortex revealed over 1,000 differentially expressed genes (DEGs). Glial transcripts were downregulated and synaptic genes upregulated. Top gene ontology terms from upregulated DEGs relate to postsynapse and ion channel function, while downregulated DEGs enriched for terms relating to metabolic function, mitochondria, and ribosomes. Levels of synaptic proteins were changed, but number and length of synaptic contacts were unaltered at 3 months. Homozygosity worsened some phenotypes including postnatal survival, weight gain delay, and increase in nuclear NACC1. This mouse model simulates a rare form of autism and will be indispensable for assessing pathophysiology and targets for therapeutic intervention.

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11. Huang Q, Ellis CL, Leo SM, Velthuis H, Pereira AC, Dimitrov M, Ponteduro FM, Wong NML, Daly E, Murphy DGM, Mahroo OA, McAlonan GM. Retinal GABAergic Alterations in Adults with Autism Spectrum Disorder. J Neurosci. 2024; 44(14).

Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA-dependent retinal response to light is altered in individuals with ASD. Light-adapted electroretinograms were recorded from 61 adults (38 males and 23 females; n = 22 ASD) in response to three stimulus protocols: (1) the standard white flash, (2) the standard 30 Hz flickering protocol, and (3) the photopic negative response protocol. Participants were administered an oral dose of placebo, 15 or 30 mg of arbaclofen (STX209, GABA(B) agonist) in a randomized, double-blind, crossover order before the test. At baseline (placebo), the a-wave amplitudes in response to single white flashes were more prominent in ASD, relative to typically developed (TD) participants. Arbaclofen was associated with a decrease in the a-wave amplitude in ASD, but an increase in TD, eliminating the group difference observed at baseline. The extent of this arbaclofen-elicited shift significantly correlated with the arbaclofen-elicited shift in cortical responses to auditory stimuli as measured by using an electroencephalogram in our prior study and with broader autistic traits measured with the autism quotient across the whole cohort. Hence, GABA-dependent differences in retinal light processing in ASD appear to be an accessible component of a wider autistic difference in the central processing of sensory information, which may be upstream of more complex autistic phenotypes.

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12. Brouwers EPM, Bergijk M, van Weeghel J, Detaille S, Kerkhof H, Dewinter J. Barriers to and Facilitators for Finding and Keeping Competitive Employment: A Focus Group Study on Autistic Adults With and Without Paid Employment. J Occup Rehabil. 2024.

PURPOSE: The aim of the study was to gain more insight into barriers to and facilitators for finding and keeping competitive employment for autistic adults. Research questions were: (1) What barriers and facilitators do autistic adults report in finding and keeping competitive employment?; and (2) What are differences and similarities between autistic adults with and without paid employment regarding barriers and facilitators for sustainable employment? METHODS: Eight focus groups were conducted (N = 64 autistic adults). Four groups included only participants without paid employment (N = 24), and four groups consisted exclusively of participants with current paid employment (including part-time, N = 40). All discussions were audiotaped and transcribed verbatim to enable inductive thematic content analysis. Data were analyzed using ATLAS.ti 9. RESULTS: Ten themes and thirty-four subthemes were found. Many were interconnected. Themes facilitating sustainable employment included a positive workplace atmosphere, a supportive supervisor, being able to do work that aligns with interests and talents, favorable physical working conditions, coaching, higher self-insight, higher self-esteem, and proactivity. Most themes and subthemes emerged from both groups. Differences between the groups were that those with paid employment seemed to have experienced more friendly workplaces and supervisors, had received better coaching in finding and keeping employment, had higher self-insight and higher self-esteem, were more assertive and proactive. CONCLUSIONS: As many (sub-)themes were interrelated, the results suggest that to improve work participation, particularly two key areas are promising: (1) to realize more friendly, well-being oriented and inclusive workplaces, and (2) to increase autistic adults’ self-insight into personal needs for positive wellbeing and self-knowledge regarding talents, wishes and well-being boundaries.

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13. Salami S, Alhalal E. Gender differences in predictors of quality of life for parents of children with Autism Spectrum disorder in Saudi Arabia. J Pediatr Nurs. 2024.

PURPOSE: Few researchers have examined gender differences in the quality of life (QoL) of parents of children with autism spectrum disorder (ASD) in diverse cultural contexts. The purpose of this study was to identify how ASD severity, affiliate stigma, perceived social support, family functioning, and coping strategies differentially predict the QoL of mothers and fathers of children with ASD in Saudi Arabia. DESIGN AND METHODS: Based on a cross-sectional research design, data were gathered between April and July 2023 from a convenience sample of 376 parents (220 mothers and 156 fathers) of children with ASD in Saudi Arabia. Welch’s t-test and regression were used to achieve the study purpose. RESULTS: Mothers of children with ASD reported lower QoL, perceived social support, and family functioning than fathers. Mothers relied on emotion-focused coping strategies, whereas fathers used problem-focused coping strategies. Furthermore, affiliate stigma, perceived social support, and family functioning significantly predicted the QoL of mothers and fathers of children with ASD. However, the severity of ASD affected only the QoL of the mothers. Problem-focused coping significantly predicted fathers’ QoL but not mothers’ QoL. CONCLUSIONS: The results highlight gender differences in the factors that predict the QoL of parents of children with ASD in Saudi Arabia. PRACTICE IMPLICATIONS: Healthcare professionals should consider parents’ gender when providing support and interventions to improve parental QoL.

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14. Al Ghamdi K, AlMusailhi J. Attention-deficit Hyperactivity Disorder and Autism Spectrum Disorder: Towards Better Diagnosis and Management. Med Arch. 2024; 78(2): 159-63.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHA) is one of the most common comorbid disorders of autism spectrum disorder (ASD) that can accompany autism, triggered by it, or be a consequence of it. OBJECTIVE: This review explored the prevalence of the comorbidity of both disorders, neurobiological background, symptoms, latest assessment methods, and therapeutic approaches. Results and Discussion: It concluded that effective assessment, diagnosis and management of ADHD in ASD children and adults is essential for this group of patients to thrive and live a good quality of life. Further research is recommended to explore the most effective intervention for such important members of our society. CONCLUSION: More studies are needed to understand the mechanisms underlying these comorbidities, and to prevent the misdiagnosis and mismanagement of these disorders. Also, to develop up to date personalized therapeutic plans for such children.

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15. Rao S, Sadybekov A, DeWitt DC, Lipka J, Katritch V, Herring BE. Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach. Mol Autism. 2024; 15(1): 12.

BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO’s GEF1 domain. ASD/ID-related missense mutations within this domain compromise glutamatergic synapse function and likely contribute to the development of ASD/ID. The number of ASD/ID cases with mutations identified within TRIO’s GEF1 domain is increasing. However, tools for accurately predicting whether such mutations are detrimental to protein function are lacking. METHODS: Here we deployed advanced protein structural modeling techniques to predict potential de novo pathogenic and benign mutations within TRIO’s GEF1 domain. Mutant TRIO-9 constructs were generated and expressed in CA1 pyramidal neurons of organotypic cultured hippocampal slices. AMPA receptor-mediated postsynaptic currents were examined in these neurons using dual whole-cell patch clamp electrophysiology. We also validated these findings using orthogonal co-immunoprecipitation and fluorescence lifetime imaging (FLIM-FRET) experiments to assay TRIO mutant overexpression effects on TRIO-RAC1 binding and on RAC1 activity in HEK293/T cells. RESULTS: Missense mutations in TRIO’s GEF1 domain that were predicted to disrupt TRIO-RAC1 binding or stability were tested experimentally and found to greatly impair TRIO-9’s influence on glutamatergic synapse function. In contrast, missense mutations in TRIO’s GEF1 domain that were predicted to have minimal effect on TRIO-RAC1 binding or stability did not impair TRIO-9’s influence on glutamatergic synapse function in our experimental assays. In orthogonal assays, we find most of the mutations predicted to disrupt binding display loss of function but mutants predicted to disrupt stability do not reflect our results from neuronal electrophysiological data. LIMITATIONS: We present a method to predict missense mutations in TRIO’s GEF1 domain that may compromise TRIO function and test for effects in a limited number of assays. Possible limitations arising from the model systems employed here can be addressed in future studies. Our method does not provide evidence for whether these mutations confer ASD/ID risk or the likelihood that such mutations will result in the development of ASD/ID. CONCLUSIONS: Here we show that a combination of structure-based computational predictions and experimental validation can be employed to reliably predict whether missense mutations in the human TRIO gene impede TRIO protein function and compromise TRIO’s role in glutamatergic synapse regulation. With the growing accessibility of genome sequencing, the use of such tools in the accurate identification of pathological mutations will be instrumental in diagnostics of ASD/ID.

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16. Rødgaard EM, Rodríguez-Herreros B, Zeribi A, Jensen K, Courchesne V, Douard E, Gagnon D, Huguet G, Jacquemont S, Mottron L. Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder. Mol Autism. 2024; 15(1): 15.

BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians’ understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians’ implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments.

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17. Wu S, Wang J, Zhang Z, Jin X, Xu Y, Si Y, Liang Y, Ge Y, Zhan H, Peng L, Bi W, Luo D, Li M, Meng B, Guan Q, Zhao J, Gao L, He Z. Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons. Mol Autism. 2024; 15(1): 14.

BACKGROUND: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3(-/-)) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α. RESULTS: We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3(-/-) mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. LIMITATIONS: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons. CONCLUSIONS: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism.

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18. Nelson AD, Catalfio AM, Gupta JP, Min L, Caballero-Florán RN, Dean KP, Elvira CC, Derderian KD, Kyoung H, Sahagun A, Sanders SJ, Bender KJ, Jenkins PM. Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites. Neuron. 2024; 112(7): 1133-49.e6.

Dysfunction in sodium channels and their ankyrin scaffolding partners have both been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). In particular, the genes SCN2A, which encodes the sodium channel Na(V)1.2, and ANK2, which encodes ankyrin-B, have strong ASD association. Recent studies indicate that ASD-associated haploinsufficiency in Scn2a impairs dendritic excitability and synaptic function in neocortical pyramidal cells, but how Na(V)1.2 is anchored within dendritic regions is unknown. Here, we show that ankyrin-B is essential for scaffolding Na(V)1.2 to the dendritic membrane of mouse neocortical neurons and that haploinsufficiency of Ank2 phenocopies intrinsic dendritic excitability and synaptic deficits observed in Scn2a(+/-) conditions. These results establish a direct, convergent link between two major ASD risk genes and reinforce an emerging framework suggesting that neocortical pyramidal cell dendritic dysfunction can contribute to neurodevelopmental disorder pathophysiology.

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19. Li H, Huang S, Jing J, Yu H, Gu T, Ou X, Pan S, Zhu Y, Su X. Correction: Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits. Nutr J. 2024; 23(1): 40.

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20. Raches CM, Hines EN, Hines AC, Scott EK. Identifying Autism Spectrum Disorder in a High-risk Follow-up Program through Quality Improvement Methodology. Pediatr Qual Saf. 2024; 9(2): e717.

INTRODUCTION: Children born prematurely are at increased risk for autism spectrum disorder (ASD). ASD can be diagnosed between 18 and 24 months of age, but access barriers and medical complexity can delay diagnosis. ASD screening was implemented in a high-risk infant follow-up program using QI methodology. The project aimed to screen 60% of children and refer 90% of those with positive screens. METHODS: The team developed a standardized workflow to administer the M-CHAT-R/F to HRIF patients between the ages of 16-22 months. Telehealth ASD assessment, using the TELE-ASD-PEDS, was conducted for those who screened positive. Monthly team meetings were held to implement change cycles and review the impact of the previous month’s change. RESULTS: Within 7 months of program implementation, ASD screening exceeded the 60% aim. The program referred 72% of patients who screened as medium/high risk on the M-CHAT-R/F. The remaining patients were not referred per provider discretion. Twenty-seven percent of patients who received an autism evaluation received an ASD diagnosis. The average age at diagnosis was 22.5 months. CONCLUSIONS: An ASD screening protocol was implemented for patients enrolled in a high-risk infant follow-up program. Patients identified as at risk for ASD received an expedited telehealth ASD evaluation. The screening protocol was maintained for 13 months and is now part of the standard workflow. Screening has been expanded to other HRIF clinics, and evaluation appointments have been added to meet access needs. QI methodology is an effective tool for implementing ASD screening and referral in multidisciplinary HRIF programs.

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21. Yin H, Jiang M, Han T, Xu X. Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications. Peptides. 2024; 176: 171211.

Animal and human studies have demonstrated that intranasal oxytocin (OT) can penetrate the brain and induce cognitive, emotional, and behavioral changes, particularly in social functioning. Consequently, numerous investigations have explored the potential of OT as a treatment for anxiety and autism, conditions characterized by social deficits. Although both subclinical and clinical studies provide converging evidence of the therapeutic effects of OT in reducing anxiety levels and improving social symptoms in autism, results are not always consistent. Additionally, the pharmacological mechanism of OT requires further elucidation for its effective clinical application. Therefore, this review aims to examine the contentious findings concerning the effects of OT on anxiety and autism, offer interpretations of the inconsistent results from the perspectives of individual differences and varying approaches to OT administration, and shed light on the underlying mechanisms of OT. Ultimately, standardization of dosage, frequency of administration, formulation characteristics, and nasal spray devices is proposed as essential for future human studies and clinical applications of OT treatment.

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22. Belaiba M, Laatar R, Borji R, Ben Salem A, Sahli S, Rebai H. Time Limited Benefits of Physical and Proprioceptive Training on Physical Fitness Components in Children With Autism Spectrum Disorders. Percept Mot Skills. 2024: 315125241244484.

In this study, we explored the immediate and three-month follow-up effects of physical training on physical fitness in children with autism spectrum disorder (ASD). We randomly assigned 20 children with ASD (age 8-11 years) into an experimental group (EG; n = 10) and a control group (CG; n = 10). The EG participated in an 8-week training program involving both strength and proprioceptive exercises (three 60-minute sessions/week), while the CG simply maintained their daily activities. We assessed physical fitness components for each participant at baseline, post-training, and at a 3-month follow-up. The physical training intervention significantly improved physical fitness of these children with ASD in terms of their flexibility (p < .001; 32.46%), lower limbs strength (p = .003; 36.98%), lower body power (p < .001; 41.78%) and functional mobility (p < .001; 25.56%). However, these addition training-induced gains were lost at follow-up for lower limbs strength (p < .001), flexibility (p < .001), and functional mobility (p = .034)). Physical training was effective for improving physical fitness in children with ASD, but the loss of these gains at three months follow-up underscored the need for continuous physical exercise.

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23. Zand MS, Spallina S, Ross A, Zandi K, Pawlowski A, Seplaki CL, Herington J, Corbett AM, Kaukeinen K, Holden-Wiltse J, Freedman EG, Alcantara L, Li D, Cameron A, Beaumont N, Dozier A, Dewhurst S, Foxe JJ. Ventilation during COVID-19 in a school for students with intellectual and developmental disabilities (IDD). PLoS One. 2024; 19(4): e0291840.

BACKGROUND: This study examined the correlation of classroom ventilation (air exchanges per hour (ACH)) and exposure to CO2 ≥1,000 ppm with the incidence of SARS-CoV-2 over a 20-month period in a specialized school for students with intellectual and developmental disabilities (IDD). These students were at a higher risk of respiratory infection from SARS-CoV-2 due to challenges in tolerating mitigation measures (e.g. masking). One in-school measure proposed to help mitigate the risk of SARS-CoV-2 infection in schools is increased ventilation. METHODS: We established a community-engaged research partnership between the University of Rochester and the Mary Cariola Center school for students with IDD. Ambient CO2 levels were measured in 100 school rooms, and air changes per hour (ACH) were calculated. The number of SARS-CoV-2 cases for each room was collected over 20 months. RESULTS: 97% of rooms had an estimated ACH ≤4.0, with 7% having CO2 levels ≥2,000 ppm for up to 3 hours per school day. A statistically significant correlation was found between the time that a room had CO2 levels ≥1,000 ppm and SARS-CoV-2 PCR tests normalized to room occupancy, accounting for 43% of the variance. No statistically significant correlation was found for room ACH and per-room SARS-CoV-2 cases. Rooms with ventilation systems using MERV-13 filters had lower SARS-CoV-2-positive PCR counts. These findings led to ongoing efforts to upgrade the ventilation systems in this community-engaged research project. CONCLUSIONS: There was a statistically significant correlation between the total time of room CO2 concentrations ≥1,000 and SARS-CoV-2 cases in an IDD school. Merv-13 filters appear to decrease the incidence of SARS-CoV-2 infection. This research partnership identified areas for improving in-school ventilation.

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24. Polzer L, Schenk M, Raji N, Kleber S, Lemler C, Kitzerow-Cleven J, Kim Z, Freitag CM, Bast N. Temporal progression of pupil dilation and gaze behavior to emotion expressions in preschoolers with autism spectrum disorder. Sci Rep. 2024; 14(1): 7843.

Previous work has shown divergent pupil dilation (PD) and gaze behavior in individuals with autism spectrum disorder (ASD), which may relate to the development of social difficulties in early life. Here, we investigated temporal dynamics of both phenotypes during naturalistic videos of a person displaying facial emotion expressions in 61 autistic and 61 non-autistic preschoolers. PD was segmented into three serial time components derived from a principal component analysis. Growth curve analysis was applied to analyze changes in looking time on eye and mouth regions over time. Groups did not differ in PD time components. Growth curve analysis revealed initially shorter looking times on the eyes and longer looking times on the mouth in autistic versus non-autistic preschoolers. However, a reversion of this pattern was observed over time, suggesting a delayed compensatory increase in eye attention during prolonged viewing periods in autistic children. Positive and negative associations of PD components and gaze behavior over time indicated a dynamic temporal relationship during emotion viewing. Our findings emphasize the need to apply time-sensitive measures in ecologically valid research, which may index etiological mechanisms of social difficulties in ASD.

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25. Morgado F, Vandewouw MM, Hammill C, Kelley E, Crosbie J, Schachar R, Ayub M, Nicolson R, Georgiades S, Arnold P, Iaboni A, Kushki A, Taylor MJ, Anagnostou E, Lerch JP. Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts. Transl Psychiatry. 2024; 14(1): 173.

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist – Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, r(POND-HBN) = -0.97; FC feature vectors, r(POND-HBN) = -0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, r(POND-HBN) = -0.99; FC feature vectors, r(POND-HBN) = -0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

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