1. Amirova A, CohenMiller A, Sandygulova A. The effects of the COVID-19 pandemic on the well-being of children with autism spectrum disorder: Parents’ perspectives. Front Psychiatry;2022;13:913902.

The COVID-19-related lockdown interrupted children’s learning progress and discontinued social learning and regular activities that children with autism spectrum disorder (ASD) rely on socially and physically. Negative consequences for children with ASD were reported far and wide. To investigate this problem in Kazakhstan, we conducted a mixed-methods study that drew on data from an online survey with 97 parents and semi-structured interviews with 14 parents. While parent-report quantitative results suggest that children were likely to experience negative impacts of the pandemic due to disrupted educational and therapeutic services, qualitative findings confirm that they have experienced an elevated mental health and behavioral challenges during the lockdown. Remote educational and therapeutic services were not helpful as families coped with pandemic-caused problems on their own. We highlight that continued support and care during and after a crisis is vital not only for children with ASD but also for the families under-resourced mentally and socially.

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2. Armin JS, Williamson HJ, Begay A, Etcitty J, Attakai A, Russell K, Baldwin JA. Adapting a Cancer Screening Education Program for Native American Women with Disabilities. Int J Environ Res Public Health;2022 (Jul 29);19(15)

Like other minoritized groups, people with disabilities experience lack of access to health care. People with intellectual and developmental disabilities (IDD), which are lifelong disabilities diagnosed in childhood requiring varying levels of support for completing daily activities, are less likely to receive preventive health care such as cancer screening. Furthermore, Native American women are less likely than White women to receive cancer screenings. In this qualitative research with Native American women with IDD, their caregivers, healthcare and service providers, and community leaders, we asked, « What are the influences on breast and cervical cancer screening for Native American women with IDD? » with the goal of adapting an existing cancer screening education program. Semi-structured in-depth interviews (N = 48) were audio recorded and transcribed verbatim for analysis. Two coders used a constant comparative method to code and revise the a priori codebook with subthemes and new codes. Results highlighted individual, interpersonal, and community/institutional influences on screening, emphasizing the individual effects of social inequity on this population, the importance of ableist bias in recommending cancer screenings, and opportunities to integrate traditional ways of knowing with allopathic medicine. Results of this work were used to adapt a cancer screening education program for Native American women with IDD.

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3. Bertuccioli A, Cardinali M, Di Pierro F, Zonzini GB, Matera MR. Ketogenic and Low FODMAP Diet in Therapeutic Management of a Young Autistic Patient with Epilepsy and Dysmetabolism Poorly Responsive to Therapies: Clinical Response and Effects of Intestinal Microbiota. Int J Mol Sci;2022 (Aug 8);23(15)

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may be an approach to consider in the management of these cases. We describe the case of a 17-year-old girl affected by ASD, reduced growth, neurological development delay, mutations in the PGM1 and EEF1A2 genes (in the absence of clinically manifested disease) and, intestinal disorders such as abdominal pain and diarrhea associated with weight loss. As she demonstrated poor responsiveness to the therapies provided, we attempted two specific dietary patterns: a ketogenic diet, followed by a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, with the aim of improving her neurological, metabolic, and intestinal symptoms through modulation of the gut microbiota’s composition. The ketogenic diet (KD) provided a reduction in Firmicutes, Bacteroidetes, and Proteobacteria. Although her intestinal symptoms improved, KD was poorly tolerated. On the other hand, the passage to a low FODMAPs diet produced a significant improvement in all neurological, intestinal, and metabolic symptoms and was well-tolerated. The following gut microbiota analysis showed reductions in Actinobacteria, Firmicutes, Lactobacilli, and Bifidobacteria. The alpha biodiversity was consistently increased and the Firmicutes/Bacteroidetes ratio decreased, reducing the extent of fermentative dysbiosis. Gut microbiota could be a therapeutic target to improve ASD-related symptoms. Further studies are needed to better understand the correlation between gut microbiota composition and ASD, and its possible involvement in the physiopathology of ASD.

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4. Boldsen S. Autism and the Sensory Disruption of Social Experience. Front Psychol;2022;13:874268.

Autism research has recently witnessed an embodied turn. In response to the cognitivist approaches dominating the field, phenomenological scholars have suggested a reconceptualization of autism as a disorder of embodied intersubjectivity. Part of this interest in autistic embodiment concerns the role of sensory differences, which have recently been added to the diagnostic criteria of autism. While research suggests that sensory differences are implicated in a wide array of autistic social difficulties, it has not yet been explored how sensory and social experience in autism relate on a phenomenological level. Given the importance of the sensory dimension of social encounters in phenomenological analyses of autism, this question must be considered crucial. This article investigates the role played by sensory differences in autistic social experience. Through a phenomenological analysis informed primarily by the philosophy of Maurice Merleau-Ponty with particular emphasis on the relation between intersubjectivity and perception, I argue that sensory differences affect the way other people appear in autistic experience on a pre-reflective level. By drawing on autistic young adults’ experiential descriptions of social encounters, this article identifies three aspects of how sensory differences affect social experiences in autism. First, social encounters manifested as sensorially disturbing, chaotic, and unpredictable events. Second, the embodied expressions of others appeared unfamiliar, threatening, and promoted a sense of detachment from the social world. Third, deliberate practices were employed to actively seek perceptual and social meaning in these disorienting social encounters. This analysis stresses the importance of understanding embodied intersubjectivity through its sensory dimensions. In addition, it indicates an important avenue for future research in exploring the potential role of practice in maintaining an intuitive grip on social meaning. By approaching social encounters as sensory and perceptual events, I emphasize how social difficulties in autism are inherently world-involving phenomena rather than a cognitive deficit reducible to the autistic person.

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5. Buijsman R, Begeer S, Scheeren AM. ‘Autistic person’ or ‘person with autism’? Person-first language preference in Dutch adults with autism and parents. Autism;2022 (Aug 11):13623613221117914.

There are different words to describe people with an autism diagnosis. For instance, we can put the person before autism (e.g. ‘person with autism’), or we can put autism before the person (e.g. ‘autistic person’). Previous research showed that autistic adults in English-speaking countries generally liked it better when autism is placed before the person. Yet, people also greatly differ in the words they like and dislike. In this study, we examined word preference in Dutch autistic adults (n = 1026; 16-84 years; 57% women) and parents of autistic children (n = 286). Via an online questionnaire, we asked our participants to select one term for autistic people that they liked best. The results showed that most adults with autism (68.3%) and parents (82.5%) preferred to put the person before autism. Younger adults, with a higher intelligence, and with more autistic traits, were a bit more likely to put autism before the person. We conclude that there are large differences in the words that people prefer. Because we found different results in our Dutch participants compared to participants in English-speaking countries, we think that the Dutch language or culture may also play a role in word preference. For now, we advise autism researchers to use both person-first and autism-first language.

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6. Butler MG, Hossain WA, Steinle J, Gao H, Cox E, Niu Y, Quach M, Veatch OJ. Connective Tissue Disorders and Fragile X Molecular Status in Females: A Case Series and Review. Int J Mol Sci;2022 (Aug 13);23(16)

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and the second most common cause after Down syndrome. FXS is an X-linked disorder due to a full mutation of the CGG triplet repeat of the FMR1 gene which codes for a protein that is crucial in synaptogenesis and maintaining functions of extracellular matrix-related proteins, key for the development of normal neuronal and connective tissue including collagen. In addition to neuropsychiatric and behavioral problems, individuals with FXS show physical features suggestive of a connective tissue disorder including loose skin and joint laxity, flat feet, hernias and mitral valve prolapse. Disturbed collagen leads to hypermobility, hyperextensible skin and tissue fragility with musculoskeletal, cardiovascular, immune and other organ involvement as seen in hereditary disorders of connective tissue including Ehlers-Danlos syndrome. Recently, FMR1 premutation repeat expansion or carrier status has been reported in individuals with connective tissue disorder-related symptoms. We examined a cohort of females with features of a connective tissue disorder presenting for genetic services using next-generation sequencing (NGS) of a connective tissue disorder gene panel consisting of approximately 75 genes. In those females with normal NGS testing for connective tissue disorders, the FMR1 gene was then analyzed using CGG repeat expansion studies. Three of thirty-nine females were found to have gray zone or intermediate alleles at a 1:13 ratio which was significantly higher (p < 0.05) when compared with newborn females representing the general population at a 1:66 ratio. This association of connective tissue involvement in females with intermediate or gray zone alleles reported for the first time will require more studies on how the size variation may impact FMR1 gene function and protein directly or in relationship with other susceptibility genes involved in connective tissue disorders.

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7. Delpire E, Ben-Ari Y. A Wholistic View of How Bumetanide Attenuates Autism Spectrum Disorders. Cells;2022 (Aug 4);11(15)

The specific NKCC1 cotransporter antagonist, bumetanide, attenuates the severity of Autism Spectrum Disorders (ASD), and many neurodevelopmental or neurodegenerative disorders in animal models and clinical trials. However, the pervasive expression of NKCC1 in many cell types throughout the body is thought to challenge the therapeutic efficacy of bumetanide. However, many peripheral functions, including intestinal, metabolic, or vascular, etc., are perturbed in brain disorders contributing to the neurological sequels. Alterations of these functions also increase the incidence of the disorder suggesting complex bidirectional links with the clinical manifestations. We suggest that a more holistic view of ASD and other disorders is warranted to account for the multiple sites impacted by the original intra-uterine insult. From this perspective, large-spectrum active repositioned drugs that act centrally and peripherally might constitute a useful approach to treating these disorders.

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8. Deng L, Rattadilok P. A Sensor and Machine Learning-Based Sensory Management Recommendation System for Children with Autism Spectrum Disorders. Sensors (Basel);2022 (Aug 3);22(15)

Sensory processing issues are one of the most common issues observed in autism spectrum disorders (ASD). Technologies that could address the issue serve a more and more important role in interventions for ASD individuals nowadays. In this study, a sensory management recommendation system was developed and tested to help ASD children deal with atypical sensory responses in class. The system employed sensor fusion and machine learning techniques to identify distractions, anxious situations, and the potential causes of these in the surroundings. Another novelty of the system included a sensory management strategy making a module based on fuzzy logic, which generated alerts to inform teachers and caregivers about children’s states and risky environmental factors. Sensory management strategies were recommended to help improve children’s attention or calm children down. The evaluation results suggested that the use of the system had a positive impact on children’s performance and its design was user-friendly. The sensory management recommendation system could work as an intelligent companion for ASD children that helps with their in-class performance by recommending management strategies in relation to the real-time information about the children’s environment.

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9. Falter-Wagner CM, Bloch C, Robles M, Horch L, Vogeley K, Georgescu AL. Figure-Disembedding Is Inferior in Non-autistic Compared to Autistic Individuals but Can Be Improved by Training. Front Psychol;2022;13:857630.

BACKGROUND: Figure-disembedding is one of the most discussed visuo-cognitive functions, in which individuals with Autism Spectrum Disorder (ASD) have been reported to outperform non-autistic individuals. A local processing bias has been assumed to underlie such superior performance patterns. The aim of the current study is to investigate whether processing preferences can be modified by procedural priming. METHOD: The current study used a procedural priming task (Navon figures) to induce more local or global processing in 25 autistic and 21 typically developing (TD) control participants, using hierarchical figures preceding the figure-disembedding task. RESULTS: Participants with ASD outperformed non-autistic individuals in the unprimed baseline task version. The performance was not modulated by priming in either direction (toward a local or global processing style) in both groups. However, the performance of TD control participants was improved by training to the same level as that observed in the ASD group. CONCLUSION: Figure-disembedding performance in ASD is superior to that in TD control participants and robust against procedural priming or training. In contrast, performance in the TD control group can be improved up to the level of the ASD group. Any studies reporting superiority in individuals with ASD in figure-disembedding should consider training effects when evaluating group differences.

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10. Franco C, Gianò M, Favero G, Rezzani R. Impairment in the Intestinal Morphology and in the Immunopositivity of Toll-like Receptor-4 and Other Proteins in an Autistic Mouse Model. Int J Mol Sci;2022 (Aug 5);23(15)

Autism spectrum disorder (ASD) identifies a neurodevelopmental disease defined by social impairments and repetitive or stereotyped behaviors. The etiology of ASD remains unclear; it primarily affects the brain, but a link between gastrointestinal (GI) diseases, inflammatory mucosal pathology and this disorder has been suggested. In particular, a central role seems to be played by an imbalance in pro-and anti-inflammatory cytokines, oxidative stress, and apoptosis. Toll-like receptor 4 (TLR4) is a protein of innate immunity responsible for the regulation and maintenance of intestinal homeostasis. Through histochemical and immunohistochemical evaluations we analyzed the intestinal morphology and the immunopositivity of TLR4 and of other pro-inflammatory and apoptotic proteins in BTBR T+Itpr3tf/J mice. Morphological data showed that the mucosal tunica presented longer intestinal villi. The length of the villi and the epithelial surface determine the exchanges of the intestinal mucosa with luminal contents, modifying the microbiota composition. The biochemical and immunohistochemical results indicated a close relationship among the increase of TLR4 and the activation of NF-kB subunits (p65 and p50) and pro-inflammatory and apoptotic proteins, such as cyclooxygenase-2, interleukin-1β, inducible nitric oxide synthase, tumor nuclear factor-alpha, caspase-3, caspase-8. These preliminary results require more in-depth study but they suggest the TLR4 signaling pathway as a possible target for therapeutic approaches to reduce GI disorders in ASD.

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11. Green HL, Shen G, Franzen RE, McNamee M, Berman JI, Mowad TG, Ku M, Bloy L, Liu S, Chen YH, Airey M, McBride E, Goldin S, Dipiero MA, Blaskey L, Kuschner ES, Kim M, Konka K, Roberts TPL, Edgar JC. Differential Maturation of Auditory Cortex Activity in Young Children with Autism and Typical Development. J Autism Dev Disord;2022 (Aug 12):1-14.

Maturation of auditory cortex neural encoding processes was assessed in children with typical development (TD) and autism. Children 6-9 years old were enrolled at Time 1 (T1), with follow-up data obtained ~ 18 months later at Time 2 (T2), and ~ 36 months later at Time 3 (T3). Findings suggested an initial period of rapid auditory cortex maturation in autism, earlier than TD (prior to and surrounding the T1 exam), followed by a period of faster maturation in TD than autism (T1-T3). As a result of group maturation differences, post-stimulus group differences were observed at T1 but not T3. In contrast, stronger pre-stimulus activity in autism than TD was found at all time points, indicating this brain measure is stable across time.

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12. Haartsen R, Mason L, Garces P, Gui A, Charman T, Tillmann J, Johnson MH, Buitelaar JK, Loth E, Murphy D, Jones EJH. Qualitative differences in the spatiotemporal brain states supporting configural face processing emerge in adolescence in autism. Cortex;2022 (Jul 14);155:13-29.

BACKGROUND: Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of non-typical neural systems. METHODS: We investigated spatial and temporal characteristics of event-related EEG responses to upright and inverted faces in a large sample of children, adolescents, and adults with and without autism. We examined topographic analyses of variance and global field power to identify group differences in the spatial and temporal response to face inversion. We then examined how quasi-stable spatiotemporal profiles – microstates – are modulated by face orientation and diagnostic group. RESULTS: Upright and inverted faces produced distinct profiles of topography and strength in the topographical analyses. These topographical profiles differed between diagnostic groups in adolescents, but not in children or adults. In the microstate analysis, the autistic group showed differences in the activation strength of normative microstates during early-stage processing at all ages, suggesting consistent quantitative differences in the operation of typical processing pathways; qualitative differences in microstate topographies during late-stage processing became prominent in adults, suggesting the increasing involvement of non-typical neural systems with processing time and over development. CONCLUSIONS: These findings suggest that early difficulties with configural face processing may trigger later compensatory processes in autism that emerge in later development.

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13. Hegvik TA, Klungsøyr K, Kuja-Halkola R, Remes H, Haavik J, D’Onofrio BM, Metsä-Simola N, Engeland A, Fazel S, Lichtenstein P, Martikainen P, Larsson H, Sariaslan A. Labor epidural analgesia and subsequent risk of offspring autism spectrum disorder and attention-deficit/hyperactivity disorder: a cross-national cohort study of 4.5 million individuals and their siblings. Am J Obstet Gynecol;2022 (Aug 13)

BACKGROUND: A recent study has suggested that labor epidural analgesia may be associated with increased rates of offspring autism spectrum disorder. Subsequent replication attempts have lacked sufficient power to confidently exclude the possibility of a small effect, and the causal nature of this association remains unknown. OBJECTIVE: This study aimed to investigate the extent to which exposure to labor epidural analgesia is associated with offspring autism spectrum disorder and attention-deficit/hyperactivity disorder following adjustments for unmeasured familial confounding. STUDY DESIGN: We identified 4,498,462 singletons and their parents using the Medical Birth Registers in Finland (cohorts born from 1987-2005), Norway (1999-2015), and Sweden (1987-2011) linked with population and patient registries. These cohorts were followed from birth until they either had the outcomes of interest, emigrated, died, or reached the end of the follow-up (at mean ages 13.6-16.8 years), whichever occurred first. Cox regression models were used to estimate country-specific associations between labor epidural analgesia recorded at birth and outcomes (eg, at least 1 secondary care diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder or at least 1 dispensed prescription of medication used for the treatment of attention-deficit/hyperactivity disorder). The models were adjusted for sex, birth year, birth order, and unmeasured familial confounders via sibling comparisons. Pooled estimates across all the 3 countries were estimated using inverse variance weighted fixed-effects meta-analysis models. RESULTS: A total of 4,498,462 individuals (48.7% female) were included, 1,091,846 (24.3%) of which were exposed to labor epidural analgesia. Of these, 1.2% were diagnosed with autism spectrum disorder and 4.0% with attention-deficit/hyperactivity disorder. On the population level, pooled estimates showed that labor epidural analgesia was associated with increased risk of offspring autism spectrum disorder (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.14, absolute risks, 1.20% vs 1.07%) and attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.20; 95% confidence interval, 1.19-1.21; absolute risks, 3.95% vs 3.32%). However, when comparing full siblings who were differentially exposed to labor epidural analgesia, the associations were fully attenuated for both conditions with narrow confidence intervals (adjusted hazard ratio [autism spectrum disorder], 0.98; 95% confidence interval, 0.93-1.03; adjusted hazard ratio attention-deficit/hyperactivity disorder, 0.99; 95% confidence interval, 0.96-1.02). CONCLUSION: In this large cross-national study, we found no support for the hypothesis that exposure to labor epidural analgesia causes either offspring autism spectrum disorder or attention-deficit/hyperactivity disorder.

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14. Jones SC. Autistics working in academia: What are the barriers and facilitators?. Autism;2022 (Aug 11):13623613221118158.

Academia appears to provide an ideal career option for autistic people: the opportunity to lock ourselves away in an ivory tower and utilise our extensive knowledge of a very specific topic. We know autistic people are underrepresented in postsecondary education, and there is a growing body of research on how to make universities more inclusive. What is missing from the literature is the voices of autistic people who have survived the university experience and gone on to become university teachers and researchers. Increasing the visibility of autistics in academia, and exploring the barriers and facilitators they experience in an academic career, is important to raise the aspirations of future university students and graduates. This study included 37 autistic academics from various disciplines and countries, exploring their perceptions of the positive and negative aspects of being an autistic in academia.

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15. Ketcheson LR, Wengrovius CM, Staples KL, Miodrag N. MYTime: A Mindfulness and Yoga Program to Promote Health Outcomes in Parents of Children With Autism Spectrum Disorder. Glob Adv Health Med;2022;11:2164957X221110154.

BACKGROUND: Parenting a child with Autism Spectrum Disorder can be stressful and result in health consequences for the caregivers, a population that is often overlooked and underserved. While mind-body interventions such as mindfulness yoga can help promote positive health outcomes, limited research has explored the impact of such a program on caregivers of children on the autism spectrum. OBJECTIVE: The primary objective of this pilot study was to evaluate the effects of a 12-week mindfulness yoga program (MYtime) on perceived stress, anxiety, and depression among urban caregivers of children on the autism spectrum. METHODS: Twenty-seven parents were randomized into either MYTime (n = 13) or the control group (n = 14). Perceived Stress Scale (PSS) and Depression, Anxiety, and Stress Scale (DASS) were administered. RESULTS: The MYTime group reported lower stress, depression and anxiety while the control group maintained similar scores across pre- and post-assessment. Following 12 weeks of participation the PSS and DASS scores improved by 25% and 49% respectively for parents in the MYTime group. In comparison, PSS scores worsened by 5% and DASS scores improved by 17% for the Control group. Differences in pre-and post-assessment scores were not significant for either group (P > .05). CONCLUSION: The results from this pilot study indicate that a mindfulness yoga program could be considered among feasible interventions aimed at improving the health of parents of children on the autism spectrum.

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16. László L, Maczelka H, Takács T, Kurilla A, Tilajka Á, Buday L, Vas V, Apáti Á. A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System. Int J Mol Sci;2022 (Aug 8);23(15)

Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene (SH3PXD2b) cause a rare developmental disorder called Frank-Ter Haar syndrome (FTHS), which leads to heart abnormalities, bone tissue defects, and reduced adiposity. We aimed to produce a human stem cell-based in vitro FTHS model system to study the effects of the loss of the Tks4 protein in different cell lineages and the accompanying effects on the cell signalome. To this end, we used CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated (Cas9)) to knock out the SH3PXD2b gene in the HUES9 human embryonic stem cell line (hESC), and we obtained stable homo- and heterozygous knock out clones for use in studying the potential regulatory roles of Tks4 protein in embryonic stem cell biology. Based on pluripotency marker measurements and spontaneous differentiation capacity assays, we concluded that the newly generated Tks4-KO HUES9 cells retained their embryonic stem cell characteristics. We propose that the Tks4-KO HUES9 cells could serve as a tool for further cell differentiation studies to investigate the involvement of Tks4 in the complex disorder FTHS. Moreover, we successfully differentiated all of the clones into mesenchymal stem cells (MSCs). The derived MSC cultures showed mesenchymal morphology and expressed MSC markers, although the expression levels of mesodermal and osteogenic marker genes were reduced, and several EMT (epithelial mesenchymal transition)-related features were altered in the Tks4-KO MSCs. Our results suggest that the loss of Tks4 leads to FTHS by altering cell lineage differentiation and cell maturation processes, rather than by regulating embryonic stem cell potential.

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17. Lerner MD, Brown CE, Sridhar A, Tschida JE, Felsman P, Libsack EJ, Kerns CM, Moskowitz LJ, Soorya L, Wainer A, Cohn E, Drahota A. Usual care for youth with autism spectrum disorder: Community-based providers’ reported familiarity with treatment practices. Front Psychiatry;2022;13:923025.

OBJECTIVE: To examine patterns and predictors of familiarity with transdisciplinary psychosocial (e.g., non-pharmacologic) practices for practitioners treating youths with autism spectrum disorder (ASD) in the United States. METHOD: Practitioners (n = 701) from behavioral, education, medical, and mental health backgrounds who worked with youth (ages 7-22) with ASD completed the Usual Care for Autism Survey, which assessed provider demographics and self-reported familiarity with transdisciplinary treatment practices for the most common referral problems of ASD. We examined relations between provider-, setting-, and client-level characteristics with familiarity of key groups of the treatment practices (practice sets). Practice sets were identified using exploratory factor analysis (EFA), and demographic predictors of practice subsets were examined using generalized estimating equations (GEE). RESULTS: The EFA yielded a three-factor solution: (1) environmental modifications/antecedent strategies; (2) behavior analytic strategies; and (3) cognitive strategies, with overall familiarity ranked in this order. Medical providers indicated the least familiarity across disciplines. More experience with ASD and treating those with intellectual disabilities predicted greater familiarity with only environmental modifications/antecedent strategies and behavior analytic, but not cognitive strategies. Experience treating low SES clients predicted familiarity with environmental modification and behavior analytic strategies while experience treating high SES clients predicted familiarity with behavior analytic and cognitive strategies. CONCLUSION: This is the first study to identify transdisciplinary, interpretable sets of practices for treating youth with ASD based on community providers’ reported familiarity. Results highlight factors associated with familiarity with practice sets, which is essential for mapping practice availability, and optimizing training and dissemination efforts for youth with ASD.

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18. Lew-Koralewicz A. Psychosocial Functioning and the Educational Experiences of Students with ASD during the COVID-19 Pandemic in Poland. Int J Environ Res Public Health;2022 (Aug 2);19(15)

Due to their individual developmental and learning needs, adolescents with autism spectrum disorder (ASD) benefit from a variety of educational, medical, and therapeutic services. During the COVID-19 pandemic, these services were discontinued or significantly reduced, which may have resulted in increased difficulties in coping with various areas of life. The purpose of this study was to explore how the pandemic affected the psychosocial and educational functioning of students with ASD. A qualitative, problem-focused interview method was used. The obtained material was subjected to interpretive phenomenological analysis. The study involved 10 secondary school students diagnosed with ASD. The assessment of the effects of the pandemic on the functioning of people with ASD is inconclusive. The respondents noted both negative and positive effects of lockdown. On the positive side, they were able to spend time with their family, isolate themselves from difficult social relationships and feel better. Among the negative effects, adolescents point to difficulties in emotional functioning-increased levels of stress and anxiety, as well as increased feelings of loneliness and difficulties with online education. The study showed the varied experiences of young people with autism during the pandemic, highlighting the significant need to support some of them in terms of their emotional, social and educational functioning.

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19. Li M, Wang Y, Tachibana M, Rahman S, Kagitani-Shimono K. Atypical structural connectivity of language networks in autism spectrum disorder: A meta-analysis of diffusion tensor imaging studies. Autism Res;2022 (Sep);15(9):1585-1602.

Patients with autism spectrum disorder (ASD) often show pervasive and complex language impairments that are closely associated with aberrant structural connectivity of language networks. However, the characteristics of white matter connectivity in ASD have remained inconclusive in previous diffusion tensor imaging (DTI) studies. The current meta-analysis aimed to comprehensively elucidate the abnormality in language-related white matter connectivity in individuals with ASD. We searched PubMed, Web of Science, Scopus, and Medline databases to identify relevant studies. The standardized mean difference was calculated to measure the pooled difference in DTI metrics in each tract between the ASD and typically developing (TD) groups. The moderating effects of age, sex, language ability, and symptom severity were investigated using subgroup and meta-regression analysis. Thirty-three DTI studies involving 831 individuals with ASD and 836 TD controls were included in the meta-analysis. ASD subjects showed significantly lower fractional anisotropy or higher mean diffusivity across language-associated tracts than TD controls. These abnormalities tended to be more prominent in the left language networks than in the right. In addition, children with ASD exhibit more pronounced and pervasive disturbances in white matter connectivity than adults. These results support the under-connectivity hypothesis and demonstrate the widespread abnormal microstructure of language-related tracts in patients with ASD. Otherwise, white matter abnormalities in the autistic brain could vary depending on the developmental stage and hemisphere. LAY SUMMARY: This meta-analysis explored abnormalities in white matter connectivity in language networks of individuals with ASD. Significantly reduced white matter integrity was found in all language-associated tracts in subjects with ASD compared with TD controls. In addition, structural disturbances of language networks in the autistic brain exhibit a leftward tendency, and more prominent abnormalities are observed in younger people with ASD than in adults.

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20. Linden A, Best L, Elise F, Roberts D, Branagan A, Tay YBE, Crane L, Cusack J, Davidson B, Davidson I, Hearst C, Mandy W, Rai D, Smith E, Gurusamy K. Benefits and harms of interventions to improve anxiety, depression, and other mental health outcomes for autistic people: A systematic review and network meta-analysis of randomised controlled trials. Autism;2022 (Aug 11):13623613221117931.

Nearly three out of four autistic people experience mental health problems such as stress, anxiety or depression. The research already done does not guide us on how best to prevent or treat mental health problems for autistic people. Our aim was to look at the benefits and harms of different interventions on mental health outcomes in autistic people. We searched all the published randomised controlled trials (RCTs) about interventions for mental health conditions in autistic people until 17 October 2020. We also searched for RCTs that were not published in peer-reviewed journals. These were obtained from registers of clinical trials online. We then combined the information from all these trials using advanced statistical methods to analyse how good the interventions are. Seventy-one studies (3630 participants) provided information for this research. The studies reported how participants were responding to the intervention for only a short period of time. The trials did not report which interventions worked for people with intellectual disability. In people without intellectual disability, some forms of cognitive behavioural therapy and mindfulness therapy may be helpful. However, further research is necessary. Many trials used medications to target core features of autism rather than targeting mental health conditions, but these medications did not help autistic people. Until we have more evidence, treatment of mental health conditions in autistic people should follow the evidence available for non-autistic people. We plan to widely disseminate the findings to healthcare professionals through medical journals and conferences and contact other groups representing autistic people.

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21. Mai TL, Chen CY, Chen YC, Chiang TW, Chuang TJ. Trans-genetic effects of circular RNA expression quantitative trait loci and potential causal mechanisms in autism. Mol Psychiatry;2022 (Aug 12)

Genetic risk variants and transcriptional expression changes in autism spectrum disorder (ASD) were widely investigated, but their causal relationship remains largely unknown. Circular RNAs (circRNAs) are abundant in brain and often serve as upstream regulators of mRNAs. By integrating RNA-sequencing with genotype data from autistic brains, we assessed expression quantitative trait loci of circRNAs (circQTLs) that cis-regulated expression of nearby circRNAs and trans-regulated expression of distant genes (trans-eGenes) simultaneously. We thus identified 3619 circQTLs that were also trans-eQTLs and constructed 19,804 circQTL-circRNA-trans-eGene regulatory axes. We conducted two different types of approaches, mediation and partial correlation tests (MPT), to determine the axes with mediation effects of circQTLs on trans-eGene expression through circRNA expression. We showed that the mediation effects of the circQTLs (trans-eQTLs) on circRNA expression were positively correlated with the magnitude of circRNA-trans-eGene correlation of expression profile. The positive correlation became more significant after adjustment for the circQTLs. Of the 19,804 axes, 8103 passed MPT. Meanwhile, we performed causal inference test (CIT) and identified 2070 circQTL-trans-eGene-ASD diagnosis propagation paths. We showed that the CIT-passing genes were significantly enriched for ASD risk genes, genes encoding postsynaptic density proteins, and other ASD-relevant genes, supporting the relevance of the CIT-passing genes to ASD pathophysiology. Integration of MPT- and CIT-passing axes further constructed 352 circQTL-circRNA-trans-eGene-ASD diagnosis propagation paths, wherein the circRNA-trans-eGene axes may act as causal mediators for the circQTL-ASD diagnosis associations. These analyses were also successfully applied to an independent dataset from schizophrenia brains. Collectively, this study provided the first framework for systematically investigating trans-genetic effects of circQTLs and inferring the corresponding causal relations in diseases. The identified circQTL-circRNA-trans-eGene regulatory interactions, particularly the internal modules that were previously implicated in the examined disorders, also provided a helpful dataset for further investigating causative biology and cryptic regulatory mechanisms underlying the neuropsychiatric diseases.

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22. Matos MB, Bara TS, Cordeiro ML. Autism Spectrum Disorder Diagnoses: A Comparison of Countries with Different Income Levels. Clin Epidemiol;2022;14:959-969.

PURPOSE: This study aimed to assess whether high-income countries have a lower mean age at the time of diagnosis of autism spectrum disorder (ASD) than low- and middle-income countries. METHOD: We reviewed studies related to ASD diagnoses and the time of first concerns in low-, middle-, and high-income countries, published in PubMed, SciELO, Lilacs, and ScienceDirect. Thirty articles were included: 13 from low- and middle-income countries and 17 from high-income countries. RESULTS: The average delay between initial concerns and diagnosis was 32.33 months, with initial concerns averaging 23.64 months and diagnosis at 55.97 months. No statistical differences were found between countries with low-, middle-, and high-income. CONCLUSIONS: This review found a considerable delay in ASD diagnosis despite an early presence of recognized signs and symptoms. It highlights the urgent need for standardized tools for early ASD diagnosis.

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23. Mohai K, Kálózi-Szabó C, Jakab Z, Fecht SD, Domonkos M, Botzheim J. Development of an Adaptive Computer-Aided Soft Sensor Diagnosis System for Assessment of Executive Functions. Sensors (Basel);2022 (Aug 6);22(15)

The main objective of the present study is to highlight the role of technological (soft sensor) methodologies in the assessment of the neurocognitive dysfunctions specific to neurodevelopmental disorders (for example, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and specific learning disorder). In many cases neurocognitive dysfunctions can be detected in neurodevelopmental disorders, some of them having a well-defined syndrome-specific clinical pattern. A number of evidence-based neuropsychological batteries are available for identifying these domain-specific functions. Atypical patterns of cognitive functions such as executive functions are present in almost all developmental disorders. In this paper, we present a novel adaptation of the Tower of London Test, a widely used neuropsychological test for assessing executive functions (in particular planning and problem-solving). Our version, the Tower of London Adaptive Test, is based on computer adaptive test theory (CAT). Adaptive testing using novel algorithms and parameterized task banks allows the immediate evaluation of the participant’s response which in turn determines the next task’s difficulty level. In this manner, the subsequent item is adjusted to the participant’s estimated capability. The adaptive procedure enhances the original test’s diagnostic power and sensitivity. By measuring the targeted cognitive capacity and its limitations more precisely, it leads to more accurate diagnoses. In some developmental disorders (e.g., ADHD, ASD) it could be very useful in improving the diagnosis, planning the right interventions, and choosing the most suitable assistive digital technological service.

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24. Nakagami A, Yasue M, Nakagaki K, Nakamura M, Kawai N, Ichinohe N. Reduced childhood social attention in autism model marmosets predicts impaired social skills and inflexible behavior in adulthood. Front Psychiatry;2022;13:885433.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication impairments and restricted and repetitive behavior. Although there is currently no established cure for ASD, early interventions for deficits of attention to other individuals are expected to reduce the progression of ASD symptoms in later life. To confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze toward other conspecifics during childhood and puberty in a three-chamber test setting using an ASD marmoset model produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in adult VPA-exposed marmosets as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and that mature animals persisted with previous strategies that required long days for acquisition to pass the test. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are consistent from childhood to adulthood, VPA-exposed marmosets will provide a valuable means of elucidating mechanisms for early intervention and contribute to the development of early therapies.

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25. Ragni B, Boldrini F, Mangialavori S, Cacioppo M, Capurso M, De Stasio S. The Efficacy of Parent Training Interventions with Parents of Children with Developmental Disabilities. Int J Environ Res Public Health;2022 (Aug 5);19(15)

Parenting children with developmental disabilities (DD) can be generally characterized by a considerable psychological burden. The effects on parental and familial psychological well-being and, consequently, on children’s developmental outcomes should not be underestimated, especially in early childhood. The current review aims to advance our understanding of the key factors (e.g., formats, sample characteristics, research design) that characterize parent training interventions, and that could be related to their outcomes, to guide researchers and clinical practitioners to develop and provide efficient programs. Studies were identified via an Internet search from three electronic databases, following PRIMSA guidelines. Studies published until November 2021 were taken into account. The initial search yielded a total of 2475 studies. Among them, 101 studies were fully reviewed. Finally, ten of the studies, which met all the inclusion criteria, formed the basis for this review. Participants’ characteristics, main features of the interventions (i.e., study design, structure, and contents), outcome variables and treatment efficacy were deeply examined and discussed. Key factors of parent training interventions with parents of children affected by DD are enlightened, to guide researchers and clinicians in the design and implementation of tailored specific programs, aimed to sustain parenting and foster children’s developmental outcomes, from early stages of life.

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26. Robinson-Agramonte MLA, Michalski B, Vidal-Martinez B, Hernández LR, Santiesteban MW, Fahnestock M. BDNF, proBDNF and IGF-1 serum levels in naïve and medicated subjects with autism. Sci Rep;2022 (Aug 12);12(1):13768.

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) promote the development and maintenance of neural circuits. Alterations in these factors might contribute to autism spectrum disorder (ASD). We asked whether serum BDNF, proBDNF, and IGF-1 levels are altered in an ASD population compared to controls. We measured serum BDNF, proBDNF, and IGF-1 immunoreactive protein in boys and girls aged 5-15 years old with mild to moderate ASD and non-autistic controls by ELISA. IGF-1 was increased in ASD serum compared to controls and was correlated with age and with CARS scores. Serum BDNF levels did not differ between groups, however, proBDNF serum levels were decreased in subjects with ASD compared to non-autistic controls. Medicated, but not unmedicated, ASD subjects exhibited lower serum proBDNF levels compared to controls, while neither IGF-1 nor BDNF levels differed between treatment groups. These data support the involvement of proBDNF and IGF-1 in the pathogenesis and treatment of autism.

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27. Sanders BW, Bedrick S, Broder-Fingert S, Brown SA, Dolata JK, Fombonne E, Reeder JA, Rivas Vazquez LA, Fuchu P, Morales Y, Zuckerman KE. Mobile and online consumer tools to screen for autism do not promote equity. Autism;2022 (Aug 11):13623613221114280.

Many parents wonder if their child might have autism. Many parents use their smartphones to answer health questions. We asked, « How easy or hard is it for parents to use their smartphones to find ‘tools’ to test their child for signs of autism? » After doing pretend parent searches, we found that only one in 10 search results were tools to test children for autism. These tools were not designed for parents who have low income or other challenges such as low literacy skills, low English proficiency, or not being tech-savvy.

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28. Schoen SA, Ferrari V, Valdez A. It’s Not Just about Bicycle Riding: Sensory-Motor, Social and Emotional Benefits for Children with and without Developmental Disabilities. Children (Basel);2022 (Aug 13);9(8)

BACKGROUND: A developing area for therapy is teaching children to ride a bicycle. Little has been written about the effectiveness of these programs. This study explored outcomes from participation in a novel bicycle riding program for children with a wide array of developmental challenges. METHOD: Two studies were conducted; a nonconcurrent, multiple baseline design with four participants and a pretest-posttest single group with 15 children. RESULTS: Study 1 participants improved on broad jump. Balance positions showed variable responses. Study 2 participants showed significant improvement on broad jump, and a trend toward significance walking forwards and backwards. Parents reported improvement in following rules, participating in daily routines, interacting with peers, and feeling good about him/herself and a change in child’s participation in community and extracurricular activities. All children improved in glide time or achieved independent riding. CONCLUSIONS: Preliminary evidence was found for the effectiveness of one approach for developing motor and social skills within the context of learning to ride a bicycle. Children over the age of 6 years were able to ride a two-wheeled bicycle at the end of the program. Participation suggested improvement in motor coordination and dynamic balance as well as changes in measures of social interaction and self-esteem.

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29. Sidig EA, Aljohani KA, Fadlalmola HA, Hamed RA. The impact of health counseling education program among Sudanese mothers on coping with autistic children. Sudan J Paediatr;2022;22(1):19-26.

Autism spectrum disorder is a collection of developmental abnormalities that can lead to significant social, communicative and behavioural challenges. A nurse is critical in establishing a parent’s level of autism awareness and coping skills. Our purpose was to evaluate how a parenting program for mothers influenced their ability to manage with autistic children. Quasi-interventional research, before and after the program was done. A total of 70 mothers of autistic children were enrolled in Khartoum State’s five autism centres. The Short Form Parenting Stress Index was used to measure the level of stress and burden experienced by mothers caring for children with autism. The study showed that 31.4% of mothers had a good score in physical care skills before the intervention and 50.0% after the intervention. The mean scores of stresses pre-training 134.48 decreased to 64.1 post training program. In the pre-training program 42.90% of the mothers used problem focus coping strategy and the post-training program represented 92.85%. The educational health and counselling program played an important role in improving mothers’ ability to cope with their autistic children.

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30. Villarreal-Martinez L, MartÍnez-Garza LE, Rodriguez-Sanchez IP, Alvarez-Villalobos N, Guzman-Gallardo F, Pope-Salazar S, Salinas-Silva C, Cepeda-Cepeda MG, Garza-Bedolla A, Dominguez-Varela IA, Villarreal-Martinez DZ, Treviño-Villarreal JH, Gomez-Almaguer D. Correlation Between CD133+ Stem Cells and Clinical Improvement in Patients with Autism Spectrum Disorders Treated with Intrathecal Bone Marrow-derived Mononuclear Cells. Innov Clin Neurosci;2022 (Apr-Jun);19(4-6):78-86.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental pathologies characterized by social and communication deficits, for which treatments are limited. Cell therapies, including intrathecal (IT) administration of bone marrow (BM) mononuclear cells (BM-MNC), improves symptoms in patients with ASD. Twenty-four patients diagnosed with ASD, according to the Diagnostic and Statistical Manual of Mental Disorders Text Revision Fourth Edition (DSM-IV-TR) criteria, were autologously treated with IT BM-MNC, and the clinical effect was evaluated using the Childhood Autism Rating Scale (CARS) on Days 30 (n=24) and 180 (n=14) post-treatment. IT BM-MNC improved clinical outcomes by Day 30 (p=0.0039), and those benefits remained and were further accentuated by Day 180 post-treatment (n=14; p=<0.0001). Clinical benefit at Days 30 (p=0.001; r= -0.51) and 180 (p=0.01; r= -0.60) posttreatment positively correlated with the enrichment of a putative BM stem cell population expressing the cluster of differentiation 133+ (CD133+) surface marker.

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31. Williams LA, LaSalle JM. Future Prospects for Epigenetics in Autism Spectrum Disorder. Mol Diagn Ther;2022 (Aug 13)

Despite decades of investigation into the genetics of autism spectrum disorder (ASD), a current consensus in the field persists that ASD risk is too heterogeneous to be diagnosed by a single set of genetic variants. As such, ASD research has broadened to include assessment of other molecular biomarkers implicated in the condition that may be reflective of environmental exposures or gene by environment interactions. Epigenetic variance, and specifically differential DNA methylation, have emerged as areas of particularly high interest to ASD, as the epigenetic markers from specific chromatin loci collectively can reflect influences of multiple genetic and environmental factors and can also result in differential gene expression patterns. This review examines recent studies of the ASD epigenome, detailing common gene pathways found to be differentially methylated in people with ASD, and considers how these discoveries may inform our understanding of ASD etiology. We also consider future applications of epigenetics in ASD research and clinical practice, focusing on substratification, biomarker development, and experimental preclinical models of ASD that test causality. In combination with other -omics approaches, epigenomics allows an improved conceptualization of the multifactorial nature of ASD, and opens future lines of inquiry for both basic research and clinical practice.

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32. Yang X, Li L, Chai X, Liu J. The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. Front Behav Neurosci;2022;16:929878.

OBJECTIVE: ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. METHODS: In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. RESULTS: The ASD group had lower ST8SIA2 gene expression levels than the control group [t ((0.05/2,143)) = 2.582, p = 0.011]. Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r (s) = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r (s) = -0.510, p = 0.004). The methylation levels of the Chr. 15: 92984625 and Chr. 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. The Chr. 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r (s) = 0.41, p = 0.039). CONCLUSION: This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD.

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33. Zheng J, Long F, Cao X, Xiong B, Li Y. Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish. Int J Mol Sci;2022 (Jul 29);23(15)

KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required for dendritic arborization in mice. However, a causative relationship between the disruption of Katnal2 function and behavioral defects has not been established. Here, we generated a katnal2 null allele in zebrafish using CRISPR/Cas9-mediated genome editing and carried out morphological and behavioral characterizations. We observed that katnal2(-/-) embryos displayed delayed embryonic development especially during the convergence and extension (CE) movement. The hatched larvae showed reduced brain size and body length. In the behavioral tests, the katnal2(-/-) zebrafish exhibited reduced locomotor activity both in larvae and adults; increased nocturnal waking activity in larvae; and enhanced anxiety-like behavior, impaired social interaction, and reduced social cohesion in adults. These findings indicate an important role for katnal2 in development and behavior, providing an in vivo model to study the mechanisms underlying the ASD related to KATNAL2 mutations.

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