1. Akol I, Izzo A, Gather F, Strack S, Heidrich S, D Óh, Villarreal A, Hacker C, Rauleac T, Bella C, Fischer A, Manke T, Vogel T. Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome. Proceedings of the National Academy of Sciences of the United States of America. 2023; 120(2): e2122467120.

Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.

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2. Angell AM, Carreon ED, Akrofi JNS, Franklin MD, Taylor EE, Miller J, Crowley C, Maher SO. Challenges and Facilitators to Telehealth Occupational Therapy for Autistic Children During COVID-19. OTJR : occupation, participation and health. 2023: 15394492221142597.

Pre-pandemic, telehealth occupational therapy (OT) for autistic children appeared promising, but research was limited. The pandemic provided a unique opportunity to investigate how clinics transitioned to telehealth. The purpose of this study was to examine barriers and facilitators that influenced delivery of OT services through telehealth for autistic children during the pandemic. We conducted semi-structured qualitative interviews with 13 participants (three administrators, six OTs, and four parents of autistic children) at three Los Angeles area clinics over a 7-month period. We used narrative and thematic analysis to identify four themes. We identified (a) Challenges and (b) Facilitators to Conducting Telehealth OT, including practical strategies for successful facilitation, and (c) Negative and (d) Positive Outcomes of Conducting Telehealth OT. As telehealth will likely remain a viable means of OT service delivery in the future, our findings provide insight into ways that it can be improved and sustained.

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3. Arzuaga AL, Edmison DD, Mroczek J, Larson J, Ragozzino ME. Prenatal stress and fluoxetine exposure in mice differentially affect repetitive behaviors and synaptic plasticity in adult male and female offspring. Behavioural brain research. 2023; 436: 114114.

Autism spectrum disorder (ASD) is characterized by social communication impairments with restricted and repetitive behaviors (RRBs). The increase in prevalence of ASD and the heterogeneity of symptom severity may arise from a complex interaction of environmental and genetic factors that alter synaptic plasticity. Maternal stress during pregnancy, which is linked to depression, may be one risk factor for an ASD phenotype in offspring. Selective serotonin reuptake inhibitor (SSRI) treatment can be effective in alleviating maternal depression but prenatal SSRI exposure itself may be a risk factor for autism in offspring. The present study investigated in C57BL/6J pregnant mice whether restraint stress (G4-18) and/or treatment with the SSRI fluoxetine (G8-18) affects autism-related behaviors and hippocampal synaptic plasticity in male and female offspring. The findings indicate that restraint stress reduces preference for sucrose reward in pregnant dams that is reversed by fluoxetine. In adult male offspring, combined prenatal stress and SSRI exposure increased self-grooming and impaired spatial reversal learning. In adult female offspring, the prenatal experiences did not affect self-grooming, but restraint stress alone or SSRI exposure alone impaired spatial reversal learning. Prenatal stress reduced anxiety-related behavior in male and female offspring. Further, LTP induced by theta-burst stimulation of Schaffer-commissural afferents in field CA1 was significantly reduced in female offspring exposed to prenatal stress alone or combination with fluoxetine. Together, these findings suggest that exposure to prenatal stress, SSRI treatment or the combination differentially affects male and female offspring in autism-like behaviors and synaptic plasticity.

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4. Atanasova E, Arévalo AP, Graf I, Zhang R, Bockmann J, Lutz AK, Boeckers TM. Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice. Molecular autism. 2023; 14(1): 1.

BACKGROUND: Autism spectrum disorder (ASD) is mainly characterized by deficits in social interaction and communication and repetitive behaviors. Known causes of ASD are mutations of certain risk genes like the postsynaptic protein SHANK3 and environmental factors including prenatal infections. METHODS: To analyze the gene-environment interplay in ASD, we combined the Shank3Δ11-/- ASD mouse model with maternal immune activation (MIA) via an intraperitoneal injection of polyinosinic/polycytidylic acid (Poly I:C) on gestational day 12.5. The offspring of the injected dams was further analyzed for autistic-like behaviors and comorbidities followed by biochemical experiments with a focus on synaptic analysis. RESULTS: We show that the two-hit mice exhibit excessive grooming and deficits in social behavior more prominently than the Shank3Δ11-/- mice. Interestingly, these behavioral changes were accompanied by an unexpected upregulation of postsynaptic density (PSD) proteins at excitatory synapses in striatum, hippocampus and prefrontal cortex. LIMITATIONS: We found several PSD proteins to be increased in the two-hit mice; however, we can only speculate about possible pathways behind the worsening of the autistic phenotype in those mice. CONCLUSIONS: With this study, we demonstrate that there is an interplay between genetic susceptibility and environmental factors defining the severity of ASD symptoms. Moreover, we show that a general misbalance of PSD proteins at excitatory synapses is linked to ASD symptoms, making this two-hit model a promising tool for the investigation of the complex pathophysiology of neurodevelopmental disorders.

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5. Bakker T, Krabbendam L, Bhulai S, Meeter M, Begeer S. Predicting academic success of autistic students in higher education. Autism : the international journal of research and practice. 2023: 13623613221146439.

What is already known about the topic?Autistic youths increasingly enter universities. We know from existing research that autistic students are at risk of dropping out or studying delays. Using machine learning and historical information of students, researchers can predict the academic success of bachelor students. However, we know little about what kind of information can predict whether autistic students will succeed in their studies and how accurate these predictions will be.What does this article add?In this research, we developed predictive models for the academic success of 101 autistic bachelor students. We compared these models to 2,465 students with other health conditions and 25,077 students without health conditions. The research showed that the academic success of autistic students was predictable. Moreover, these predictions were more precise than predictions of the success of students without autism.For the success of the first bachelor year, concerns with aptitude and study choice were the most important predictors. Participation in pre-education and delays at the beginning of autistic students’ studies were the most influential predictors for second-year success and delays in the second and final year of their bachelor’s program. In addition, academic performance in high school was the strongest predictor for degree completion in 3 years.Implications for practice, research, or policyThese insights can enable universities to develop tailored support for autistic students. Using early warning signals from administrative data, institutions can lower dropout risk and increase degree completion for autistic students.

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6. Davies J, Heasman B, Livesey A, Walker A, Pellicano E, Remington A. Access to employment: A comparison of autistic, neurodivergent and neurotypical adults’ experiences of hiring processes in the United Kingdom. Autism : the international journal of research and practice. 2023: 13623613221145377.

Autistic people are less likely to have a job than non-autistic people. One reason for this may be that hiring processes (e.g. job applications, interviews) can be challenging for autistic people. To better understand the experiences of hiring processes in the United Kingdom, we asked 225 autistic, 64 neurodivergent (but not autistic) and 64 adults with no reported area of neurodivergence questions about their experiences using an online survey. We found a range of similarities and differences in responses. For example, participants in all three groups were frustrated with the focus on social skills in recruitment and said they wanted more practical methods (e.g. work trials) that help them show their skills and abilities. Autistic and otherwise neurodivergent participants discussed the importance of the environment (e.g. the interview/assessment room) in improving experiences. Participants also discussed how employers can impact whether somebody decides to disclose their diagnosis or needs – or not. Autistic people experienced some barriers to successful recruitment that non-autistic people did not. For example, autistic people felt they had to hide their autistic traits to gain employment and many autistic people were worried about being discriminated against if they disclosed that they were autistic during the hiring process. To make experiences better, our participants said that employers should offer candidates different recruitment methods and give them more information about the hiring process. They also said employers should improve their understanding of autism and other hidden disabilities so they know the challenges that people might face during recruitment.

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7. Greenlee JL, Hickey E, Stelter CR, Huynh T, Hartley SL. Profiles of the parenting experience in families of autistic children. Autism : the international journal of research and practice. 2023: 13623613221147399.

Research shows that parents of autistic children, on average, are stressed; however, there is likely an array of factors that characterize the parenting experience in the context of autism other than stress. Understanding the diversity in the parenting experiences of both mothers and fathers of autistic children is important in the development of family-based intervention. A total of 188 co-habiting couples with an autistic child described their parenting experiences using a series of questionnaires examining their feelings of stress, parenting competence, and parenting attitudes and behaviors. We then sorted responses into profiles-three for mothers and four for fathers. We found that children of parents who reported the least amount of stress, highest feeling of competence, and use of responsive and directive parenting strategies (the Adaptive profile) had children with the least severe behavioral problems and autism symptoms. It was not necessary for both parents to be in the Adaptive category for child emotional and behavioral problems to less severe. We found that children did just as well when one parent was Adaptive compared with when both parents fell into this category.

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8. Han E, Scior K, Heath E, Umagami K, Crane L. Development of stigma-related support for autistic adults: Insights from the autism community. Autism : the international journal of research and practice. 2023: 13623613221143590.

Many autistic adults experience public stigma, which refers to negative attitudes and treatment from others. Because of that, some autistic adults may also apply unhelpful beliefs to themselves, which is known as internalised stigma. There is some evidence that both public stigma and internalised stigma are linked to poorer mental health in autistic adults. Clearly, it is crucial to change how society thinks and acts towards autistic people. There are several programmes that are trying to do this. But as change can be slow, support may also be needed to help autistic people cope with and challenge stigma. Using an online survey, we gathered the views of 144 autistic adults and parents/caregivers of autistic people in the United Kingdom on whether a stigma support programme for autistic adults is needed and, if so, what it should ‘look’ like. Most participants felt it was important for autistic adults to have support in managing stigma because of the harmful effects that stigma has on mental health and the challenges that autistic adults face in disclosing their diagnosis. However, participants were also concerned that such a programme could convey the message that autistic people, rather than society, need to change. Participants suggested that the programme should be positive and practical, helping autistic adults to understand and accept themselves, as well as learn context-specific strategies for responding to stigma and/or disclosing their diagnosis. They also stressed that the programme should be flexible and inclusive, recognising that autistic adults have very different needs and preferences.

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9. Hudry K, Smith J, Pillar S, Varcin KJ, Bent CA, Boutrus M, Chetcuti L, Clark A, Dissanayake C, Iacono T, Kennedy L, Lant A, Robinson Lake J, Segal L, Slonims V, Taylor C, Wan MW, Green J, Whitehouse AJO. The Utility of Natural Language Samples for Assessing Communication and Language in Infants Referred with Early Signs of Autism. Research on child and adolescent psychopathology. 2023.

Natural Language Sampling (NLS) offers clear potential for communication and language assessment, where other data might be difficult to interpret. We leveraged existing primary data for 18-month-olds showing early signs of autism, to examine the reliability and concurrent construct validity of NLS-derived measures coded from video-of child language, parent linguistic input, and dyadic balance of communicative interaction-against standardised assessment scores. Using Systematic Analysis of Language Transcripts (SALT) software and coding conventions, masked coders achieved good-to-excellent inter-rater agreement across all measures. Associations across concurrent measures of analogous constructs suggested strong validity of NLS applied to 6-min video clips. NLS offers benefits of feasibility and adaptability for validly quantifying emerging skills, and potential for standardisation for clinical use and rigorous research design.

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10. Ivarsson M, Danielsson H, Andersson AK, Gothilander J, Granlund M. Structural validity and internal consistency of the Strengths and Stressors in Parenting (SSF) Questionnaire in parents of children with developmental disabilities. Scandinavian journal of psychology. 2023.

The current study investigated the structural validity and internal consistency of the Strengths and Stressors (SSF) questionnaire. The SSF is used in Swedish habilitation services to measure the positive and negative consequences that the fostering of a child with a developmental disability can have on family functioning in six domains: parent’s feelings and attitudes, social life, family finances, relationship to the other parent, siblings, and professional support. The proposed six-factor model was tested with confirmatory factor analysis with data collected from 291 parents of children with developmental disabilities. The six-factor model had an acceptable fit according to most fit indices, but two items were non-significant. Overall, the internal consistency was acceptable or good. The SSF, with the proposed six-factor solution, can be a useful tool when assessing parental perspectives on the impacts of having a child with a developmental disability in clinical settings and research.

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11. Liloia D, Manuello J, Costa T, Keller R, Nani A, Cauda F. Atypical local brain connectivity in pediatric autism spectrum disorder? A coordinate-based meta-analysis of regional homogeneity studies. European archives of psychiatry and clinical neuroscience. 2023.

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age [Formula: see text] 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.

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12. Maltman N, Hilvert E, Friedman L, Sterling A. Comparison of Linguistic Error Production in Conversational Language Among Boys With Fragile X Syndrome + Autism Spectrum Disorder and Autistic Boys. Journal of speech, language, and hearing research : JSLHR. 2023: 1-18.

PURPOSE: Expressive language impairments are common among school-age boys with fragile X syndrome (FXS) and autistic boys. Given the high co-occurrence of autism spectrum disorder (ASD) among individuals with FXS, cross-condition comparisons can elucidate the specificity of such impairments as they relate to ASD. Language samples can provide fruitful information regarding individuals’ grammatical skills in less structured formats relative to standardized measures. This study examined grammatical errors produced during a conversational language sample among 20 boys with FXS and co-occurring ASD (FXS + ASD) and 19 autistic boys matched on ASD severity. METHOD: Language samples were coded for omissions and errors at the word and utterance levels. Participants’ grammatical errors were also compared to separate mental age-matched and mean length of utterance-matched boys from a reference database. RESULTS: Boys with FXS + ASD and autistic boys produced similar rates of errors across all categories. Relative to their matched comparison groups, boys with FXS + ASD and autistic boys produced significantly more omissions during conversation. CONCLUSIONS: These findings suggest that omissions may be a unique grammatical marker associated with the ASD phenotype. Further examination of omissions across diagnostic groups would aid in clarifying the specificity of omissions in the language phenotype of ASD.

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13. McMaughan DJD, Imanpour S, Mulcahy A, Jones J, Criss MM. Mental health-related hospitalizations among adolescents and emerging adults with autism in the United States: A retrospective, cross-sectional analysis of national hospital discharge data. Autism : the international journal of research and practice. 2023: 13623613221143592.

Autistic young people are more likely to have mental health conditions, like depression and bipolar disorder, than people without autism. These mental health issues sometimes lead to hospitalizations, which can be expensive and traumatic. Because of this, we wanted to understand mental health-related hospitalizations among autistic young people aged 10-20. We found that the main mental health reasons for the hospitalization of autistic young people were neurodevelopmental, disruptive, depressive, and bipolar disorders. These hospitalizations cost an average of US$7401.23 per stay, for a total of US$106 million in service delivery costs in 2016. Mental health-related hospitalizations were compared between young people with autism, young people with complex and chronic conditions, and young people with no chronic conditions. Autistic young people were almost 11 times more likely to be hospitalized for mental health reasons than young people with complex and chronic conditions, and two times more likely than young people with no complex and chronic conditions. We believe the United States needs better community-based mental health care for young people with autism.

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14. Meguid NA, Hashem HS, Ghanem MH, Helal SA, Semenova Y, Hashem S, Hashish A, Chirumbolo S, Elwan AM, Bjørklund G. Evaluation of Branched-Chain Amino Acids in Children with Autism Spectrum Disorder and Epilepsy. Molecular neurobiology. 2023.

Autism spectrum disorder (ASD) and epilepsy run hand-to-hand in their pathophysiology. Epilepsy is not an uncommon finding in patients with ASD. The aim of the present study was to identify the metabolic abnormalities of BCAAs (leucine, isoleucine, and valine) in children with ASD with and without seizures in comparison with neurotypical controls. Also, this study aimed to investigate the presence of epileptiform discharges on electroencephalography (EEG) in ASD patients and to describe the types and frequency of seizures observed. The study included 90 children aged 2-7 years, 30 of whom were diagnosed with both ASD and epilepsy. The other 30 children were diagnosed as ASD without epilepsy, and a comparable 30 normally developed children served as a control group. The groups were matched by age and gender. All patients were referred to the Autism Disorders Clinic for interviews and examinations. The Childhood Autism Rating Scale (CARS) was applied to all study participants to assess the degree of autism. The present study results show that all types of seizures may be identified in ASD children. The median serum levels of BCAAs were lower in ASD children with and without epilepsy than in neurotypical controls. This opens the door for discussion about new etiologies and better categorizations of ASD based on genotype and genetic abnormalities detected. More studies with larger samples are needed to understand ASD better and to more reliable evaluate the association between ASD, EEG changes, seizures, and BCAAs.

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15. Montiel-Nava C, Montenegro MC, Ramirez AC, Valdez D, Rosoli A, Garcia R, Garrido G, Cukier S, Rattazzi A, Paula CS. Age of autism diagnosis in Latin American and Caribbean countries. Autism : the international journal of research and practice. 2023: 13623613221147345.

An earlier diagnosis of autism spectrum disorder might lead to earlier intervention. However, people living in Latin American and Caribbean countries do not have much knowledge about autism spectrum disorder symptoms. It has been suggested that the older a child is when diagnosed, the fewer opportunities he or she will have to receive services. We asked 2520 caregivers of autistic children in six different Latin America and Caribbean Countries, the child’s age when they noticed some developmental delays and their child’s age when they received their first autism spectrum disorder diagnosis. Results indicate that, on average, caregivers were concerned about their child’s development by 22 months of age; however, the diagnosis was received when the child was 46 months of age. In addition, older children with better language abilities and public health coverage (opposed to private health coverage) were diagnosed later. On the contrary, children with other medical problems and more severe behaviors received an earlier diagnosis. In our study, children were diagnosed around the time they entered formal schooling, delaying the access to early intervention programs. In summary, the characteristics of the autistic person and the type of health coverage influence the age of diagnosis in children living in Latin America and Caribbean Countries.

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16. Rehn AK, Caruso VR, Kumar S. The effectiveness of animal-assisted therapy for children and adolescents with autism spectrum disorder: A systematic review. Complementary therapies in clinical practice. 2023; 50: 101719.

BACKGROUND: and purpose Individuals with autism spectrum disorder (ASD) experience difficulty with communication, learning, behaviour, and social interactions. Animal-assisted therapy (AAT) is a growing alternative and complementary therapy for ASD. This review aims to investigate the effectiveness of AAT for children and adolescents with ASD in the domains of cognitive, social, emotional, behavioural, and physical. METHODS: A systematic search of databases (Medline, Emcare, Embase, Cochrane Library, PsycINFO, PsycARTICLES, Scopus, ERIC and OTseeker) was conducted in March 2022. Grey literature was also explored which included searching Trove database and the first 10 pages of Google, as well as pearling reference lists of included studies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The methodological quality of the included studies was assessed using a modified Joanna Briggs Institute Review Form for Randomised Controlled Trials. A descriptive synthesis was undertaken due to heterogeneity within the evidence base. RESULTS: Seven randomised controlled/clinical controlled trials with moderate methodological quality were included in this review. Overall, participation in AAT identified positive trends in the cognitive, social, emotional, behavioural, and physical domains. Despite the positive outcomes, implementation of AAT should be taken with caution as there are currently no standardised frameworks due to heterogeneity within the intervention protocols and outcome measures. CONCLUSION: AAT may have positive effects across a multitude of outcomes in the management of ASD for children and adolescents. However, the current literature has considerable methodological concerns which should be addressed by future research.

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17. Russo DA, Blair KC. Using the high-probability instructional sequence to improve initiation and completion of low-probability instructions in young autistic children. Research in developmental disabilities. 2023; 134: 104422.

This study examined the use of the high-probability (high-p) instructional sequence during pre-academic or academic activities for three young children diagnosed with autism spectrum disorder (ASD) served in public elementary schools. Specifically, we examined the effects of the high-p instructional sequence on the children’s initiation and completion of low-probability (low-p) instructions, implemented by their classroom teachers. A nonconcurrent multiple-baseline design across participants was used to evaluate the intervention outcomes. The results indicated that the high-p instructional sequence may be an effective antecedent-based intervention for autistic children who typically initiate the low-p instructions but have difficulty completing the instructions. A strong magnitude of effect was shown for initiation across children. For one child, initiation and completion increased during high-p, and the improvement was maintained above criterion levels when high-p instructions in sequence were faded. For two children, we found high levels of initiation but variable performance in completion during high-p. The use of programmed reinforcement for one child suggests that for autistic children who do not often initiate the low-p instructions, the addition of programmed reinforcement may be needed to increase completion of low-probability instructions.

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18. Zhang L, Xu X, Ma L, Wang X, Jin M, Li L, Ni H. Zinc Water Prevents Autism-Like Behaviors in the BTBR Mice. Biological trace element research. 2023.

This study aims to explore the effects of zinc water on autism-like behavior, convulsion threshold, and neurogenesis in ASD model animals. This study used the young BTBR ASD mouse model to explore the effect of a 6-week zinc water supplementation on ASD-like behaviors such as repetitive behavior and social communication disorder, seizure threshold, and the correlation with excitability regulation. The mice were divided into four groups of normal controls (B6) and models (BTBR) who did and did not receive zinc supplementation in water (B6, B6 + zinc, BTBR, and BTBR + zinc). For morphological changes in the hippocampus, we selected two indicators: hippocampal mossy fiber sprouting and neurogenesis. ASD-like behavior testing, seizure threshold determination, Timm staining, and neurogenesis-related assays-represented by Ki67 and DCX-were performed after 6 weeks of zinc supplementation. Our results show that zinc water can prevent autism-like behavior, reduce susceptibility to convulsions, and increase the proliferation of hippocampal progenitor cells in BTBR mice but has less effect on mossy fiber sprouting and neural progenitor cell differentiation. Zinc water reduces autism-like behavior in a partially inherited autism model mice-BTBR-which may be associated with hippocampal neural precursor cell proliferation and reversed hyperexcitability.

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