1. Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R, Alhawamdeh R. Role of gastrointestinal health in managing children with autism spectrum disorder. World journal of clinical pediatrics. 2023; 12(4): 171-96.

Children with autism spectrum disorders (ASD) or autism are more prone to gastrointestinal (GI) disorders than the general population. These disorders can significantly affect their health, learning, and development due to various factors such as genetics, environment, and behavior. The causes of GI disorders in children with ASD can include gut dysbiosis, immune dysfunction, food sensitivities, digestive enzyme deficiencies, and sensory processing differences. Many studies suggest that numerous children with ASD experience GI problems, and effective management is crucial. Diagnosing autism is typically done through genetic, neurological, functional, and behavioral assessments and observations, while GI tests are not consistently reliable. Some GI tests may increase the risk of developing ASD or exacerbating symptoms. Addressing GI issues in individuals with ASD can improve their overall well-being, leading to better behavior, cognitive function, and educational abilities. Proper management can improve digestion, nutrient absorption, and appetite by relieving physical discomfort and pain. Alleviating GI symptoms can improve sleep patterns, increase energy levels, and contribute to a general sense of well-being, ultimately leading to a better quality of life for the individual and improved family dynamics. The primary goal of GI interventions is to improve nutritional status, reduce symptom severity, promote a balanced mood, and increase patient independence.

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2. Alshehri S, Ahmad SF, Albekairi NA, Alqarni SS, Al-Harbi NO, Al-Ayadhi LY, Attia SM, Alfardan AS, Bakheet SA, Nadeem A. Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury. Toxics. 2023; 11(9).

Autism spectrum disorder (ASD) is a complex developmental disorder in children that results in abnormal communicative and verbal behaviors. Exposure to heavy metals plays a significant role in the pathogenesis or progression of ASD. Mercury compounds pose significant risk for the development of ASD as children are more exposed to environmental toxicants. Increased concentration of mercury compounds has been detected in different body fluids/tissues in ASD children, which suggests an association between mercury exposure and ASD. Thioredoxin1 (Trx1) and thioredoxin reductase1 (TrxR1) redox system plays a crucial role in detoxification of oxidants generated in different immune cells. However, the effect of methylmercury and the Nrf2 activator sulforaphane on the Trx1/TrxR1 antioxidant system in neutrophils of ASD subjects has not been studied previously. Therefore, this study examined the effect of methylmercury on Trx1/TrxR1 expression, TrxR activity, nitrotyrosine, and ROS in neutrophils of ASD and TDC subjects. Our study shows that Trx1/TrxR1 protein expression is dysregulated in ASD subjects as compared to the TDC group. Further, methylmercury treatment significantly inhibits the activity of TrxR in both ASD and TDC groups. Inhibition of TrxR by mercury is associated with upregulation of the Trx1 protein in TDC neutrophils but not in ASD neutrophils. Furthermore, ASD neutrophils have exaggerated ROS production after exposure to methylmercury, which is much greater in magnitude than TDC neutrophils. Sulforaphane reversed methylmercury-induced effects on neutrophils through Nrf2-mediated induction of the Trx1/TrxR1 system. These observations suggest that exposure to the environmental toxicant methylmercury may elevate systemic oxidative inflammation due to a dysregulated Trx1/TrxR1 redox system in the neutrophils of ASD subjects, which may play a role in the progression of ASD.

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3. Binder MS, Bordey A. Semi-natural housing rescues social behavior and reduces repetitive exploratory behavior of BTBR autistic-like mice. Scientific reports. 2023; 13(1): 16260.

Environmental enrichment confers numerous benefits when implemented in murine models and can reduce behavioral symptomatology in models of disease, such as autism spectrum disorder (ASD). However, previous work did not examine the impact of early-life environmental enrichment on each core feature of ASD. We thus implemented a social and physical enrichment at birth, modeling a semi-natural housing, and examined its impact on communicative, social, sensory, and repetitive behaviors using BTBR (autistic-like) and C57BL/6 J (B6, wildtype) mice, comparing them to standard housing conditions. We found that environmental enrichment alleviated the social deficit of juvenile BTBR mice and reduced their repetitive exploratory behavior but did not affect their rough versus smooth texture preference nor the number of maternal isolation-induced pup calls. Environmental enrichment only affected the call characteristics of B6 mice. One interpretation of these data is that early-life environmental enrichment has significant therapeutic potential to treat selective core features of ASD. Another interpretation is that reducing environmental complexity causes selective behavioral deficits in ASD-prone mice suggesting that current standard housing may be suboptimal. Overall, our data illustrate the extent to which the environment influences behavior and highlights the importance of considering housing conditions when designing experiments and interpreting behavioral results.

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4. de Jong JR, Dijkerman HC, Keizer A. Autistic Traits Related to the Importance of Interpersonal Touch and Appreciation of Observed Touch during COVID-19 Social Distancing. International journal of environmental research and public health. 2023; 20(18).

Studies have confirmed the significance of touch for psychological wellbeing. Social distancing regulations during the COVID-19 pandemic reduced people’s ability to engage in interpersonal touch and caused increased an appreciation for observed touch, as well as a longing for touch within the neurotypical population. Yet, while the impact of social distancing and the importance of touch are evident in neurotypical individuals, it remains unclear how these factors manifest in autistic individuals. Previous research has related high levels of autistic traits to reduced levels of perceived pleasantness of touch and a reduced interest in interpersonal touch. Our study aimed to examine the differences in the appreciation of observed touch and longing for touch during social distancing between individuals with low and high levels of autistic traits. We conducted an online survey on autistic traits, the appreciation of observed CT-optimal touch and longing for touch. Consistent with our predictions, our results confirmed that individuals with high levels of autistic traits evaluated videos depicting CT-optimal touch less favorably compared to those with lower scores on autistic traits. Additionally, only the group with low levels of autistic traits exhibited a longing for touch during social distancing, whereas the group with high levels of autistic traits did not. The results provide insights in the appreciation of touch in relation to autistic traits during the unique circumstances of the COVID-19 pandemic.

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5. de Oliveira C, Tanner B. Estimating Cumulative Health Care Costs of Childhood and Adolescence Autism Spectrum Disorder in Ontario, Canada: A Population-Based Incident Cohort Study. PharmacoEconomics – open. 2023.

BACKGROUND: Few studies have estimated cumulative health care costs post-diagnosis for individuals with autism spectrum disorder (ASD). OBJECTIVES: Using an incidence-based approach, the objective of this analysis was to estimate cumulative costs of ASD to the Ontario health care system of children and adolescents. METHODS: Using administrative health records from Ontario, Canada’s most populous province, a retrospective, population-based, incident cohort study of children and adolescents aged 0-19 years old diagnosed with ASD was undertaken to estimate cumulative health care costs of ASD to the health care system from 2010 to 2019. Cumulative health care costs in 2021 Canadian dollars (CAD) from diagnosis to death or end of observation period were estimated using a consistent estimator based on the inverse probability weighting technique. Cumulative health care costs (and respective 95% confidence intervals [CI]) were estimated for 1, 5 and 10 years post-diagnosis by sex, age group and health service. RESULTS: In 2010, there were 2867 diagnosed cases of ASD; in 2019, the number of incident cases had risen to 6072. The first year (i.e., 1-year) post-diagnosis cost of ASD was $4710.18 CAD (95% CI 4560.28-4860.08); just under a third of costs were for physician services. Total cumulative 5- and 10-year discounted costs were $16,025.95 CAD (15,371.64-16,680.26) and $32,635.76 CAD (28,906.94-36,364.58), respectively. Mean costs were higher for females and older age groups. CONCLUSIONS: These results suggest that costs of ASD are high in the year of diagnosis and then increase at a steady rate thereafter. This information will help with future resource planning within the health care sector to ensure individuals with ASD are supported once their diagnosis is established.

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6. Frazier TW, Chetcuti L, Al-Shaban FA, Haslam N, Ghazal I, Klingemier EW, Aldosari M, Whitehouse AJO, Youngstrom EA, Hardan AY, Uljarević M. Categorical versus dimensional structure of autism spectrum disorder: A multi-method investigation. JCPP advances. 2023; 3(2): e12142.

BACKGROUND: A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi-method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD). METHOD: Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non-ASD/NDD controls (aggregate Ns = 512-16,755; ages 1.5-22). Scores from four distinct phenotype measures formed composite « indicators » of the latent ASD construct. The primary indicator set included eye gaze metrics from seven distinct social stimulus paradigms. Logistic regressions were used to combine gaze metrics within/across paradigms, and derived predicted probabilities served as indicator values. Secondary indicator sets were constructed from clinical observation and parent-report measures of ASD symptoms. Indicator sets were submitted to taxometric- and latent class analyses. RESULTS: Across all indicator sets and analytic methods, there was strong support for categorical structure corresponding closely to ASD diagnosis. Consistent with notions of substantial phenotypic heterogeneity, the ASD category had a wide range of symptom severity. Despite the examination of a large sample with a wide range of IQs in both genders, males and children with lower IQ were over-represented in the ASD category, similar to observations in diagnosed cases. CONCLUSIONS: Our findings provide strong support for categorical structure corresponding closely to ASD diagnosis. The present results bolster the use of well-diagnosed and representative ASD groups within etiologic and clinical research, motivating the ongoing search for major drivers of the ASD phenotype. Despite the categorical structure of ASD, quantitative symptom measurements appear more useful for examining relationships with other factors.

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7. Hollywood JB. Integrative Therapies for Magnesium and Calcium Deficiency in a Food Insecure, Autism Subject: A Case Report. Integrative medicine (Encinitas, Calif). 2023; 22(4): 28-32.

INTRODUCTION: Individuals facing homelessness with autism spectrum disorder (ASD) are at increased risk for food insecurity. Financial difficulties increase the demand to donate blood plasma to support hardship. Excessive blood plasma donations may lead to micronutrient deficiencies exacerbating deficits derived from poor food habits. Therapies that may support these populations in securing foods and improving lifestyle habits may be diet, supplements, nutrition education, and holistic lifestyle recovery support group. CASE DESCRIPTION: A homeless, 31-yr-old Caucasian female with ASD presenting with magnesium and calcium deficiencies, and ten year history of blood plasma donations sought medical nutrition therapy. Over 6 months and in conjunction with physician prescriptions, interventions were augmented with magnesium and calcium supporting vegetables; reduction of dairy, fast foods, and ultra-processed foods; nutrition education and holistic lifestyle recovery support group. Upon final visit, the patient had remarkable improvement of nutrition knowledge and food budgeting, in-kitchen housing stability, food access, and stress reduction. CONCLUSION: Nutrition education improves nutrition knowledge and food budgeting facilitating food access, while holistic lifestyle recovery support groups can influence healthier living and stress reduction in homeless patients with ASD. Population-based clinical studies should be done to understand the role of these conjunctive therapies to support nutrition practice.

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8. Li L, Su YE, Hou W, Zhou M, Xie Y, Zou X, Li M. Expressive Language Profiles in a Clinical Screening Sample of Mandarin-Speaking Preschool Children With Autism Spectrum Disorder. Journal of speech, language, and hearing research : JSLHR. 2023: 1-22.

PURPOSE: This cross-sectional study aimed to depict expressive language profiles and clarify lexical-grammatical interrelationships in Mandarin-speaking preschoolers with autism spectrum disorder (ASD) during the administration of the simplified Chinese Psychoeducational Profile-Third Edition screening. METHOD: We collected naturalistic language samples from 81 (74 boys, seven girls) 2- to 7-year-old (M(age) = 55.6 months, SD = 15.17) Mandarin-speaking children with ASD in clinician-child interactions. The child participants were divided into five age subgroups with 12-month intervals according to their chronological age. Computer-assisted part-of-speech tagging, constituency analysis, and dependency analysis addressed the developmental trajectories of early lexical and grammatical growth in each age subgroup. RESULTS: Significant within-ASD differences were observed in content words, function words, and lexical categories. Nouns and verbs were the predominant lexical categories, while noun types overwhelmed verb types in children over 3 years old. The grammatical development of 5- to 6-year-old Mandarin-speaking children with ASD was better than that of 3- to 4-year-old children. The trends of syntactic structures, grammatical relations, and grammatical complexity in each age group were similar. CONCLUSIONS: Mandarin-speaking preschoolers with ASD produce more lexicons with increasing age. They preserve the noun bias as a universal mechanism in early lexical learning. Moreover, their developmental trajectories of grammatical growth were comparable in each age subgroup. In addition, their lexicons and grammar were synchronically developed during early language acquisition.

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9. Mashayekhi P, Omrani MD, Tonekaboni SH, Dehghanifard A. A novel de novo canonical splice site mutation in the PTCH1 gene in a male patient with mild psychomotor retardation and autistic traits: a case report. Human genome variation. 2023; 10(1): 26.

Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare autosomal dominant disorder caused by mutations in the tumor suppressor gene PTCH1 with complete penetrance and variable expressivity characterized by a broad spectrum of developmental anomalies and a predisposition to neoplasms. Herein, we report a novel de novo splice site mutation in the PTCH1 gene related to mild developmental delay and autistic traits in a 4-year-old male patient.

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10. Nowak BVR, Bowen WD, den Heyer CE, Lang SLC, Lidgard DC. Ontogeny of movement patterns in naïve grey seal pups inhabiting a complex continental shelf ecosystem. PloS one. 2023; 18(9): e0290707.

Most vertebrate offspring must transition from the relative security of parental care (nutrition and protection) to independent foraging. Offspring face many challenges during this critical period, particularly in species where parental care ends at weaning, such as the grey seal (Halichoerus grypus). We studied the development of movement behaviour in naïve grey seal pups from their first trips to sea to about five months of age. Twenty-five (12 males and 13 females) newly-weaned pups were fitted with satellite-linked GPS tags on Sable Island, Nova Scotia, Canada in January 2016. The influence of fixed effects (pup size, sex, week) and the random effect of pup identity on trip characteristics were examined. Movement behaviour was analyzed using a move persistence mixed-effects model. Habitat use was highly variable among individuals and covered much of the geographic distribution of the population. Unlike older juveniles, subadults, and adults in this population, most naïve pups used multiple haulout sites to begin and end trips. There was little evidence of area-restricted search behaviour during trips, suggesting that naïve pups were using an opportunistic foraging tactic that may result in more variable foraging success than that of older, experienced animals. Naïve pups made longer trips with longer haulout durations between them than observed for older greys seals. Males and females differed in some trip characteristics, but sex effects were small over the first few months of life. Offspring size at weaning was not a useful predictor of trip characteristics. Move persistence of grey seal pups was initially high and then decreased over time as individuals gained experience. Both intrinsic and extrinsic factors were influential on the movements of grey seal pups. Greater body length at weaning, longer duration spent on shore after weaning, shallower water column depth, and farther distance from shore were all associated with lower move persistence. Female grey seal pups had lower move persistence than males. Overall, the movements of naïve grey seal pups during the first few months of life were characterized by extensive exploration, but move persistence decreased over time suggesting they may be using an exploration-refinement foraging tactic.

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11. Santos FH, Sood P, Gan DRY, Lansang N, Devos H, Heyn PC. Physical Activity for Persons with Intellectual and Developmental Disabilities: A Support Guide for Health Care Professionals. Archives of physical medicine and rehabilitation. 2023.

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12. Shao L, Fu C, Chen X. A heterogeneous graph convolutional attention network method for classification of autism spectrum disorder. BMC bioinformatics. 2023; 24(1): 363.

BACKGROUND: Autism spectrum disorder (ASD) is a serious developmental disorder of the brain. Recently, various deep learning methods based on functional magnetic resonance imaging (fMRI) data have been developed for the classification of ASD. Among them, graph neural networks, which generalize deep neural network models to graph structured data, have shown great advantages. However, in graph neural methods, because the graphs constructed are homogeneous, the phenotype information of the subjects cannot be fully utilized. This affects the improvement of the classification performance. METHODS: To fully utilize the phenotype information, this paper proposes a heterogeneous graph convolutional attention network (HCAN) model to classify ASD. By combining an attention mechanism and a heterogeneous graph convolutional network, important aggregated features can be extracted in the HCAN. The model consists of a multilayer HCAN feature extractor and a multilayer perceptron (MLP) classifier. First, a heterogeneous population graph was constructed based on the fMRI and phenotypic data. Then, a multilayer HCAN is used to mine graph-based features from the heterogeneous graph. Finally, the extracted features are fed into an MLP for the final classification. RESULTS: The proposed method is assessed on the autism brain imaging data exchange (ABIDE) repository. In total, 871 subjects in the ABIDE I dataset are used for the classification task. The best classification accuracy of 82.9% is achieved. Compared to the other methods using exactly the same subjects in the literature, the proposed method achieves superior performance to the best reported result. CONCLUSIONS: The proposed method can effectively integrate heterogeneous graph convolutional networks with a semantic attention mechanism so that the phenotype features of the subjects can be fully utilized. Moreover, it shows great potential in the diagnosis of brain functional disorders with fMRI data.

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13. Singh A, Lawler CP, Walker VR, Pelch KE, Garton AE, Rooney AA, Haugen AC. Becoming aWARE: The Development of a Web-Based Tool for Autism Research and the Environment. Journal of xenobiotics. 2023; 13(3): 492-9.

A sharp rise in autism spectrum disorder (ASD) prevalence estimates, beginning in the 1990s, suggested factors additional to genetics were at play. This stimulated increased research investment in nongenetic factors, including the study of environmental chemical exposures, diet, nutrition, lifestyle, social factors, and maternal medical conditions. Consequently, both peer- and non-peer-reviewed bodies of evidence investigating environmental contributors to ASD etiology have grown significantly. The heterogeneity in the design and conduct of this research results in an inconclusive and unwieldy ‘virtual stack’ of publications. We propose to develop a Web-based tool for Autism Research and the Environment (aWARE) to comprehensively aggregate and assess these highly variable and often conflicting data. The interactive aWARE tool will use an approach for the development of systematic evidence maps (SEMs) to identify and display all available relevant published evidence, enabling users to explore multiple research questions within the scope of the SEM. Throughout tool development, listening sessions and workshops will be used to seek perspectives from the broader autism community. New evidence will be indexed in the tool annually, which will serve as a living resource to investigate the association between environmental factors and ASD.

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14. Stojsavljević A, Lakićević N, Pavlović S. Does Lead Have a Connection to Autism? A Systematic Review and Meta-Analysis. Toxics. 2023; 11(9).

Environmental pollutants, particularly toxic trace metals with neurotoxic potential, have been related to the genesis of autism. One of these metals that stands out, in particular, is lead (Pb). We conducted an in-depth systematic review and meta-analysis of peer-reviewed studies on Pb levels in biological materials retrieved from autistic children (cases) and neurotypical children (controls) in this work. A systematic review was conducted after the careful selection of published studies according to established criteria to gain a broad insight into the higher or lower levels of Pb in the biological materials of cases and controls, and the findings were then strengthened by a meta-analysis. The meta-analysis included 17 studies (hair), 13 studies (whole blood), and 8 studies (urine). The overall number of controls/cases was 869/915 (hair), 670/755 (whole blood), and 344/373 (urine). This meta-analysis showed significantly higher Pb levels in all three types of biological material in cases than in controls, suggesting a higher body Pb burden in autistic children. Thus, environmental Pb exposure could be related to the genesis of autism. Since no level of Pb can be considered safe, the data from this study undoubtedly point to the importance of regularly monitoring Pb levels in autistic children.

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15. Stone-Heaberlin M, Blackburn A, Qian C. Caregiver education programme on intellectual and developmental disabilities: An acceptability and feasibility study in an academic medical setting. Child: care, health and development. 2023.

BACKGROUND: Children and adolescents with intellectual and developmental disabilities (I/DD), including autism spectrum disorder, benefit from a variety of specialized interventions. However, there are barriers that impact families’ ability to access such services for their children. While not intended as a replacement for individualized or group-based interventions, educational classes may be an option in providing supplemental resources and support to families of individuals with I/DD. This study was a programme evaluation that examined the feasibility and acceptability of a Caregiver Education Program that was created in an outpatient specialty clinic of an academic medical centre, designed to provide educational information on a variety of topics relevant to children and adolescents with I/DD (e.g., toilet training, understanding behaviour and managing anxiety). METHOD: The review included 1027 participants from 40 classes led by licensed clinicians, trainees, and/or experienced caregivers. Classes occurred approximately one time per month over the course of three-and-a-half years and targeted caregivers of children and adolescents with I/DD and community-based professionals in the field of I/DD. Participants were able to attend one or multiple classes, based on their interest in the given topic. Participants were asked to complete post-training surveys at the end of each session as part of ongoing programme evaluation. RESULTS: Participants reported a high level of satisfaction and increased knowledge as a result of participating in classes, and higher knowledge gained and higher satisfaction for in-person classes compared to virtual classes. CONCLUSIONS: This programme is one model of education delivery with high acceptability and feasibility, designed to support families and increase access to information beyond specialized interventions. Future directions include improving the model of programme data collection, examination of the programme’s generalization to practice and to other communities, and an emphasis on culturally responsive curricula.

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16. Tang X, Feng C, Zhao Y, Zhang H, Gao Y, Cao X, Hong Q, Lin J, Zhuang H, Feng Y, Wang H, Shen L. A study of genetic heterogeneity in autism spectrum disorders based on plasma proteomic and metabolomic analysis: multiomics study of autism heterogeneity. MedComm. 2023; 4(5): e380.

Genetic heterogeneity poses a challenge to research and clinical translation of autism spectrum disorder (ASD). In this study, we conducted a plasma proteomic and metabolomic study of children with ASD with and without risk genes (de novo mutation) and controls to explore the impact of genetic heterogeneity on the search for biomarkers for ASD. In terms of the proteomic and metabolomic profiles, the groups of children with ASD carrying and those not carrying de novo mutation tended to cluster and overlap, and integrating them yielded differentially expressed proteins and differential metabolites that effectively distinguished ASD from controls. The mechanisms associated with them focus on several common and previously reported mechanisms. Proteomics results highlight the role of complement, inflammation and immunity, and cell adhesion. The main pathways of metabolic perturbations include amino acid, vitamin, glycerophospholipid, tryptophan, and glutamates metabolic pathways and solute carriers-related pathways. Integrating the two omics analyses revealed that L-glutamic acid and malate dehydrogenase may play key roles in the pathogenesis of ASD. These results suggest that children with ASD may have important underlying common mechanisms. They are not only potential therapeutic targets for ASD but also important contributors to the study of biomarkers for the disease.

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