1. Alanazi MM, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Mazroua HA, Aldossari AA, Almutairi MM, Albekairi TH, Hussein MH, Al-Hamamah MA, Ahmad SF. Cadmium Exposure Is Associated with Behavioral Deficits and Neuroimmune Dysfunction in BTBR T(+) Itpr3tf/J Mice. International journal of molecular sciences. 2023; 24(7).

Autism spectrum disorders (ASD) are neurobehavioral disabilities characterized by impaired social interactions, poor communication skills, and restrictive/repetitive behaviors. Cadmium is a common heavy metal implicated in ASD. In this study, we investigated the effects of Cd exposure on BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model. We looked for changes in repetitive behaviors and sociability through experiments. We also explored the molecular mechanisms underlying the effects of Cd exposure, focusing on proinflammatory cytokines and pathways. Flow cytometry measured IL-17A-, IL-17F-, IL-21-, TNF-α-, STAT3-, and RORγt-expressing CD4(+) T cells from the spleens of experimental mice. We then used RT-PCR to analyze IL-17A, IL-17F, IL-21, TNF-α, STAT3, and RORγ mRNA expression in the brain. The results of behavioral experiments showed that Cd exposure significantly increased self-grooming and marble-burying in BTBR mice while decreasing social interactions. Cd exposure also significantly increased the number of CD4(+)IL-17A(+), CD4(+)IL-17F(+), CD4(+)IL-21(+), CD4(+)TNF-α(+), CD4(+)STAT3(+), and CD4(+)RORγt(+) cells, while upregulating the mRNA expression of the six molecules in the brain. Overall, our results suggest that oral exposure to Cd aggravates behavioral and immune abnormalities in an ASD animal model. These findings have important implications for ASD etiology and provide further evidence of heavy metals contributing to neurodevelopmental disorders through proinflammatory effects.

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2. Asmare RF, Taye FN, Kotecho MG, Mishna F, Regehr C. Towards a « New Mothering » Practice? The Life Experiences of Mothers Raising a Child with Autism in Urban Ethiopia. International journal of environmental research and public health. 2023; 20(7).

Autism spectrum disorder (ASD) is a complex neurological and developmental disorder that has seen an increase in prevalence over the past two decades, particularly in low and middle-income countries. The purpose of the current paper is to examine the experiences of mothers in Ethiopia raising a child with ASD through employing a qualitative research design involving semi-structured interviews with twenty mothers. The experiences of mothers in this study fell into three thematic areas: (1) grieving and experiencing other emotions arising from the diagnosis of their child; (2) developing, understanding and defining autism; and (3) accepting the diagnosis and developing coping strategies for raising their child. The findings revealed that raising a child with autism introduced a new lifelong experience to mothers’ everyday lives, profoundly changing their parenting role and transforming their view of mothering. Recognition of the experience of « new mothering » and mothers’ meaning-making process, stress, coping mechanisms and resilience is critical to informing policies, programs, counseling and other therapeutic efforts to assist children with autism and their families for social workers in Ethiopia and those working with the Ethiopian diaspora in other regions of the world.

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3. Bagatell N, Lamarche E, Klinger L. Roles of Caregivers of Autistic Adults: A Qualitative Study. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 2023; 77(2).

IMPORTANCE: Understanding the roles of caregivers of autistic adults is important given the increasing number of autistic adults and their ongoing need for various supports. OBJECTIVE: To address the following question: What roles do caregivers enact to support autistic adults? DESIGN: This study had a descriptive qualitative design. Caregivers completed a two-part interview. Data analyses included extracting narratives and a multiple-step coding process that resulted in the identification of three main caregiving themes. PARTICIPANTS: Thirty-one caregivers of autistic adults. FINDINGS: Three main themes that reflected caregiving roles were identified: (1) managing daily living needs, (2) obtaining services and supports, and (3) providing invisible supports. Each theme comprised three subthemes. The roles were enacted regardless of the autistic adults’ age, gender, adaptive behavior scores, employment status, or residential status. CONCLUSIONS AND RELEVANCE: Caregivers enacted many roles to support their autistic adult to participate in meaningful occupation. Occupational therapy practitioners can support autistic people across the lifespan in areas such as daily living, leisure, and executive function strategies to decrease the need for caregiving or services. They can also support caregivers as they manage the present and plan for the future. What This Article Adds: This study provides descriptions that illustrate the complexity of caregiving for autistic adults. With an understanding of the many roles that caregivers enact, occupational therapy practitioners can provide services that support both autistic people and their caregivers. Positionality Statement: We recognize that use of person-first versus identity-first language is a source of debate and controversy. We have chosen to use identity-first language, for two reasons. First, studies indicate that person with autism is the term least preferred by autistic people (e.g., Botha et al., 2021). Second, autistic is the term used by the majority of our participants during interviews.

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4. Brett JD, Peden B, Preece DA, Whitehouse A, Becerra R, Maybery MT. Assessing Restricted and Repetitive Behaviours in Online-Sampled Autistic and Non-autistic Individuals: Factor Structure of the Repetitive Behaviours Questionnaire for Adults (RBQ-2A). Journal of autism and developmental disorders. 2023.

The Repetitive Behaviours Questionnaire for Adults (RBQ-2A) measures two factors of restricted and repetitive behaviours (RRBs) associated with autism. However, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides four criteria for RRBs: repetitive motor behaviours, insistence on sameness, restricted interests, and interest in sensory aspects of the environment (or atypical sensitivity). The current paper aimed to examine whether the RBQ-2A is a psychometrically sound measure of these four factors. Study 1 had university students (N = 368) complete the RBQ-2A and other related measures online and revealed that the RBQ-2A can assess the factors highlighted in the DSM-5 and that these four factors comprise a general RRB construct. Study 2 had individuals disclosing a diagnosis of autism (N = 283) complete the RBQ-2A and other related measures online and supported that this four-factor structure provided good psychometric properties. While the current paper provides findings for an online autistic population, further research is needed to generalize these findings to autistic individuals less likely to partake in online studies (e.g., those with intellectual or language disabilities). Overall, the results suggest that the RBQ-2A reliably and validly assesses RRBs.

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5. Brito A, Franco F, Brentani H, Beltrão-Braga PCB. Assessment of vulnerability dimensions considering Family History and environmental interplay in Autism Spectrum Disorder. BMC psychiatry. 2023; 23(1): 254.

BACKGROUND: Despite previous studies have recently shown Autism Spectrum Disorders (ASD) as having a strong genetics background, over a minimum environmental background, no study up to date has investigated the interplay between genetics and environment. METHODS: We have collected data regarding Family History (FH) and Environmental Factors (EF) from 2,141 individuals with ASD and their caretakers throughout Brazil, based on an online questionnaire. Most of the ASD individuals were males (81%) and the average age was 02 years minimum for males and females, and the maximum age was 41 years for males and 54 for females. People from all states in Brazil have answered the questionnaire. Genetic inheritance was obtained based on the declared FH of Psychiatric and Neurological diagnosis. As for EF, exposure to risk factors during pregnancy was considered, like infections, diabetes, drugs/chemicals exposure, socioeconomic, and psychological factors. Respondents were invited to answer the questionnaire in lectures given throughout Brazil, and by the social networks of the NGO « The Tooth Fairy Project ». A Multiple Correspondence Analysis (MCA) was conducted to search vulnerability dimensions, and a Cluster Analysis was conducted to classify and identify the subgroups. RESULTS: Regarding EF, social and psychological exposures contributed to the first two dimensions. Concerning FH, the first dimension represented psychiatric FH, while the second represented neurological FH. When analyzed together, EF and FH contributed to two new dimensions: 1. psychiatric FH, and 2. a psychosocial component. Using Cluster Analysis, it was not possible to isolate subgroups by genetic vulnerability or environmental exposure. Instead, a gradient of psychiatric FH with similar contributions of EF was observed. CONCLUSION: In this study, it was not possible to isolate groups of patients that correspond to only one component, but rather a continuum with different compositions of genetic and environmental interplay.

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6. Burke MM, Taylor JL. To better meet the needs of autistic people, we need to rethink how we measure services. Autism : the international journal of research and practice. 2023; 27(4): 873-5.

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7. Chamtouri M, Merghni A, Salazar N, Redruello B, Gaddour N, Mastouri M, Arboleya S, de Los Reyes-Gavilán CG. An Overview on Fecal Profiles of Amino Acids and Related Amino-Derived Compounds in Children with Autism Spectrum Disorder in Tunisia. Molecules (Basel, Switzerland). 2023; 28(7).

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by the impairment of social interaction, difficulties in communication, and repetitive behaviors. Alterations in the metabolism of amino acids have been reported. We performed a chromatographic analysis of fecal amino acids, ammonium, biogenic amines, and gamma aminobutyric acid (GABA) in Tunisian autistic children from 4 to 10 years, and results were compared with their siblings (SIB) and children from the general population (GP). ASD presented significantly higher levels of fecal amino acids than SIB and GP; differences being more pronounced in younger (4-7 years) than in older (8-10 years) individuals whereas no changes were found for the remaining compounds. Lower levels of histidine were the only difference related with severe symptoms of autism (CARS scale). A linear discriminant analysis (LDA) based on fecal amino acid profiles clearly separated ASD, SIB, and GP at 4 to 7 years but not at more advanced age (8-10 years), evidencing more pronounced alterations in younger children. The relationship of fecal amino acids with autism needs deeper research integrating blood analytical parameters, brain metabolism, and intestinal microbiota. Fecal amino acids could be targeted for designing personalized diets to prevent or minimize cognitive impairments associated with ASD.

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8. Dargenio VN, Dargenio C, Castellaneta S, De Giacomo A, Laguardia M, Schettini F, Francavilla R, Cristofori F. Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder. Nutrients. 2023; 15(7).

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a « leaky gut. » A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota-gut-brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut-brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.

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9. Feng J, Shan L, Miao C, Xue Y, Yue X, Jia F. The association of vitamin A, zinc and copper levels with clinical symptoms in children with autism spectrum disorders in Jilin Province, China. BMC pediatrics. 2023; 23(1): 173.

BACKGROUND: This study evaluated vitamin A (VA), copper (Cu), and zinc (Zn) levels in the population with autism spectrum disorder (ASD) in Jilin Province, China. Furthermore, we examined their links to core symptoms and neurodevelopment, as well as gastrointestinal (GI) comorbidities and sleep disorders. METHODS: This study included 181 children with autism and 205 typically developing (TD) children. The participants had not taken vitamin/mineral supplements in the prior three months. High-performance liquid chromatography was used to measure serum VA levels. By using inductively coupled plasma-mass spectrometry, Zn and Cu concentrations in plasma were determined. Importantly, the Childhood Autism Rating Scale, the Social Responsiveness Scale, and the Autism Behavior Checklist were used to measure core ASD symptoms. However, the Griffith Mental Development Scales-Chinese were used to measure neurodevelopment. GI comorbidities and sleep abnormalities were assessed with the 6 Item-Gastrointestinal Severity Index and Children’s Sleep Habits Questionnaire, respectively. Children with ASD with GI issues were grouped according to severity (low GI severity and high GI severity groups). RESULTS: (i) The difference in VA, Zn, Cu levels and the Zn/Cu ratio between ASD and TD children is small. But children with ASD had lower VA levels and Zn/Cu ratio, higher Cu levels than TD children. Cu levels in children with ASD were associated with the severity of core symptoms. (ii) Children with ASD were much more likely than their TD counterparts to suffer from GI comorbidities or sleep problems. Furthermore, it was observed that high GI severity was associated with lower levels of VA, whereas low GI severity was associated with higher levels of VA. (iii) The children with ASD who had both lower VA and lower Zn/Cu ratio had more severe scores on the Autism Behavior Checklist, but not on other measures. CONCLUSION: Children with ASD had lower VA and Zn/Cu ratio, and higher Cu levels. Cu levels in children with ASD were weakly correlated with one subscale on social or self-help. ASD children with lower VA levels may face more serious GI comorbidities. Children with ASD combined VA-Zn/Cu lower had more severe core symptoms. TRIAL REGISTRATION: Registration number: ChiCTR-OPC-17013502. Date of registration: 2017-11-23.

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10. Fombonne E. Editorial: Is autism overdiagnosed?. Journal of child psychology and psychiatry, and allied disciplines. 2023; 64(5): 711-4.

After attention was drawn in the late 1960s to the poor reproducibility of psychiatric diagnosis between clinicians, methods and procedures used to diagnose psychiatric disorders were greatly improved. Sources of variance contributing to the poor reliability of psychiatric diagnosis were identified that included: information variance (how clinicians go about enquiring about symptoms), interpretation variance (how clinicians weigh the observed symptomatology towards diagnostic formulations), and criterion variance (how clinicians arrange symptom constellations to generate specific diagnoses). To improve the reliability of diagnosis, progresses were made in two major directions. First, diagnostic instruments were developed to standardize the way symptoms are elicited, evaluated, and scored. These diagnostic interviews were either highly structured for use in large-scale studies (e.g. the DIS), by lay interviewers without a clinical background, and with a style of questioning that emphasized adherence to the exact wording of probes, reliance on closed questions with simple response formats (Yes/No) and recording respondents’ answers without interviewer’s judgment contribution. By contrast, semi-structured interviews (e.g. the SADS) were designed to be used by clinically trained interviewers and adopted a more flexible, conversational style, using open-ended questions, utilizing all behavioral descriptions generated in the interview, and developing scoring conventions that called upon the clinical judgment of the interviewer. Second, diagnostic criteria and algorithms were introduced in nosographies in 1980 for the DSM and soon after in ICD. Algorithm-derived diagnoses could subsequently be tested for their validity using follow-up, family history, treatment response studies, or other external criteria.

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11. Fulceri F, Gila L, Caruso A, Micai M, Romano G, Scattoni ML. Building Bricks of Integrated Care Pathway for Autism Spectrum Disorder: A Systematic Review. International journal of molecular sciences. 2023; 24(7).

An integrated plan within a defined care pathway for the diagnosis, continuative interventions, and periodic redefinition of care of autistic people is essential for better outcomes. Challenges include delivering services across all domains or life stages and effective coordination between health/social care providers and services. Further, in the ‘real world’, service provision varies greatly, and in many settings is significantly weighted towards diagnosis and children’s services rather than treatment and support or adult care. This study aims to identify existing care pathways for Autism Spectrum Disorder (ASD) from referral to care management after diagnosis. The study reviewed the international literature in PubMed and PsycInfo databases and collected information on care for autistic individuals from the Autism Spectrum Disorders in Europe (ASDEU) project partners. The study found that published data mainly focused on specific components of care pathways rather than an integrated and coordinated plan of care and legislative indications. They should be aimed at facilitating access to the services for support and the inclusiveness of autistic individuals. Given the need for care addressing the complex and heterogeneous nature of ASD, effective coordination between different health/social care providers and services is essential. It is also suggested that research priority should be given to the identification of an integrated care pathway ‘model’ centered around case management, individualization, facilitation, support, continuous training and updating, and quality management.

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12. Girianelli VR, Tomazelli J, Silva C, Fernandes CS. Early diagnosis of autism and other developmental disorders, Brazil, 2013-2019. Revista de saude publica. 2023; 57: 21.

OBJECTIVE: To investigate the factors associated with the early diagnosis of autism and other types of pervasive developmental disorder (PDD) in children treated at the Psychosocial Care Center for Children and Adolescents of the Unified Health System, from 2013 to 2019,in Brazil. METHODS: An exploratory cross-sectional study, based on data from the Record of Outpatient Health Actions (RAAS) of the first appointment of children aged 1 to 12 years. The gross (RRg) and adjusted (RRa) relative risks and respective 95% confidence intervals (95%CI) were estimated using the Poisson regression model with robust variance estimation. RESULTS: Of the 22,483 children included in the study, the majority were male (81.9%), lived in the same municipality where they were diagnosed (96.8%) and in the Southeast region (57.7%). Early diagnosis was higher for childhood autism (RRg = 1.48; 95%CI 1.27-1.71) , PDD without subtype designation (RRg = 1.55; 95%CI 1.34-1.80), other PDD (RRg = 1.48; 95%CI 1.21-1.81) and PDD not otherwise specified (RRg = 1.44; 95%CI 1.22-1.69) than for atypical autism. Children residing in the same municipality where the diagnosis was made had a higher rate of early diagnosis (RRg = 1.31; 95%CI 1.10-1.55) than the others; as well as those referred by primary care (RRg = 1.51; 95%CI 1.37-1.68) and by spontaneous demand (RRg = 1.45; 95%CI 1.31-1.61) than those from other types of referral. Early diagnosis was higher from 2014 and lower in the North region than in the other regions. In the multiple analysis, the magnitude of RRa was similar to that of RRg. CONCLUSIONS: Early identification of autism and other PDD has improved in Brazil, but it still represents about 30% of the diagnoses made. The variables included in the model were significant, but still explain little of the early diagnosis of children with autism and other PDD.

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13. Hilton CL, Ratcliff K, Hong I. Predictors of Participation Difficulties in Autistic Children. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 2023; 77(2).

IMPORTANCE: Participation in meaningful occupations supports quality of life and health. Because quality of life is lower in autistic children than in children without this diagnosis, it is important to consider aspects contributing to the participation difficulties this population experiences. OBJECTIVE: To identify predictors of participation difficulties in a large data set from autistic children to inform professionals about potential intervention targets. DESIGN: Retrospective cross-sectional design using a large data set with multivariate regression models for home life, friendships, classroom learning, and leisure activities. SETTING: 2011 Survey of Pathways to Diagnosis and Services data set. PARTICIPANTS: Parents or caregivers of 834 autistic children with co-occurring intellectual disability (ID) and 227 autistic children with no ID. RESULTS: The strongest participation predictors within the scope of occupational therapy practice were sensory processing, emotional regulation, behavioral variables, and social variables. Our results are consistent with those of smaller previous studies and indicate the importance of addressing these areas in occupational therapy intervention in line with client priorities. CONCLUSION AND RELEVANCE: Focusing interventions with autistic children on sensory processing, emotional regulation, behavioral skills, and social skills to address their underlying neurological processing can support their increased participation in home life, friendships, classroom learning, and leisure activities. What This Article Adds: Our findings support a focus in occupational therapy interventions on sensory processing and social skills to increase activity participation in autistic children with and without ID. Emotional regulation and behavioral skills can be supported by interventions that target cognitive flexibility. Positionality Statement: This article uses the identity-first language autistic people. This nonableist language describes their strengths and abilities and is a conscious decision. This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel et al., 2021; Kenny et al., 2016).

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14. Kaur H, Chinna K, Sivanesom R. Sleep disturbances and their association with behaviour in children with autism spectrum disorder: A cross-sectional study. Singapore medical journal. 2023.

INTRODUCTION: In this study, we aimed to determine the prevalence of sleep disturbances among children aged 2-5 years with autism spectrum disorder (ASD) and their association with behaviour in these children. METHOD: A cross-sectional study was conducted at Hospital Tunku Azizah, Kuala Lumpur, Malaysia, from June 2020 to December 2020. Children between 2 and 5 years old, diagnosed with ASD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, were recruited. Two parent-reported questionnaires, the Children’s Sleep Habits Questionnaire (CSHQ) and the Child Behaviour Checklist (CBCL/1.5-5), were used to assess sleep and behaviour, respectively. Children were classified as good sleepers (CSHQ score <41) and poor sleepers (CSHQ score ≥41). Poor sleepers were further categorised into those with mild or moderate to severe sleep problems (based on the 75(th) percentile CSHQ score). The CBCL/1.5-5 raw scores were converted to standardise T-scores, yielding scores of three summary scales (internalising, externalising and total problems). RESULTS: A total of 134 children participated in this study. Their mean age was 42.23 ± 9.95 months, and 81.3% were males. Mean CSHQ score was 49.77 ± 6.90, and 93.3% were poor sleepers. Internalising, externalising and total problems scores were significantly higher in poor sleepers (62, 59 and 62, respectively) compared to good sleepers (56, 47 and 51, respectively). Children with moderate to severe sleep problems had clinical scores of internalising (median 65) and externalising (median 65) problems, as compared to mild sleep problems (median internalising score 61, median externalising score 57). CONCLUSION: Sleep disturbances are prevalent among children with ASD. Poor sleep quality is associated with more behavioural problems.

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15. Kay C, Leonard H, Smith J, Wong K, Downs J. Genotype and sleep independently predict mental health in Rett syndrome: an observational study. Journal of medical genetics. 2023.

BACKGROUND: Rett syndrome is a genetically caused neurodevelopmental disorder associated with severe impairments and complex comorbidities. This study examined predictors of anxiety and depression in Rett syndrome, including genotype. METHODS: The International Rett Syndrome Database, InterRett, was the data source for this observational study. Associations between genotype, functional abilities, comorbidities, anxiety and depression were estimated with univariate and multivariate regression models. An additional regression model for anxiety included use of an anxiety medication as a predictor variable. RESULTS: The sample included 210 individuals aged 6-51 years of whom 54 (25.7%) were on psychotropic medication for anxiety or depression. Individuals with the p.Arg294* variant had the highest anxiety scores, as did those with insomnia or excessive daytime sleepiness, irrespective of anxiety medication use. Individuals with the p.Arg306Cys variant had the lowest depression scores, as did those with insomnia or excessive daytime sleepiness. CONCLUSION: Findings indicated that genotype and sleep have implications for mental health in Rett syndrome, suggesting that anticipatory guidance and proactive management of poor sleep could improve mental health. More research is needed to understand the effects of psychometric medications, which cannot be inferred from this cross-sectional study.

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16. Kildal ESM, Quintana DS, Szabo A, Tronstad C, Andreassen O, Nærland T, Hassel B. Heart rate monitoring to detect acute pain in non-verbal patients: a study protocol for a randomized controlled clinical trial. BMC psychiatry. 2023; 23(1): 252.

BACKGROUND: Autism entails reduced communicative abilities. Approximately 30% of individuals with autism have intellectual disability (ID). Some people with autism and ID are virtually non-communicative and unable to notify their caregivers when they are in pain. In a pilot study, we showed that heart rate (HR) monitoring may identify painful situations in this patient group, as HR increases in acutely painful situations. OBJECTIVES: This study aims to generate knowledge to reduce the number of painful episodes in non-communicative patients’ everyday lives. We will 1) assess the effectiveness of HR as a tool for identifying potentially painful care procedures, 2) test the effect of HR-informed changes in potentially painful care procedures on biomarkers of pain, and 3) assess how six weeks of communication through HR affects the quality of communication between patient and caregiver. METHODS: We will recruit 38 non-communicative patients with autism and ID residing in care homes. ASSESSMENTS: HR is measured continuously to identify acutely painful situations. HR variability and pain-related cytokines (MCP-1, IL-1RA, IL-8, TGFβ1, and IL-17) are collected as measures of long-term pain. Caregivers will be asked to what degree they observe pain in their patients and how well they believe they understand their patient’s expressions of emotion and pain. Pre-intervention: HR is measured 8 h/day over 2 weeks to identify potentially painful situations across four settings: physiotherapy, cast use, lifting, and personal hygiene. INTERVENTION: Changes in procedures for identified painful situations are in the form of changes in 1) physiotherapy techniques, 2) preparations for putting on casts, 3) lifting techniques or 4) personal hygiene procedures. DESIGN: Nineteen patients will start intervention in week 3 while 19 patients will continue data collection for another 2 weeks before procedure changes are introduced. This is done to distinguish between specific effects of changes in procedures and non-specific effects, such as caregivers increased attention. DISCUSSION: This study will advance the field of wearable physiological sensor use in patient care. TRIAL REGISTRATION: Registered prospectively at ClinicalTrials.gov (NCT05738278).

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17. Kim SA, Jang EH, Lee J, Cho SH. Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats. International journal of molecular sciences. 2023; 24(7).

Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. VPA affects neurotransmission and gene expression through epigenetic mechanisms by acting as a histone deacetylase inhibitor and has been used to establish animal models of autism spectrum disorder (ASD). However, studies on the long-term effects of early exposure to VPA on glucocorticoid and neurosteroid synthesis in the brain are lacking. Therefore, this study aimed to investigate the long-term changes in metabolic alterations and gene expression regulation according to sex, using metabolic steroid profiling data from cerebral cortex samples of rats four weeks after VPA exposure (400 mg/kg). In neonatal VPA-exposed models, estradiol levels decreased, and cytochrome P450 19A1 gene (Cyp19a1) expression was reduced in the prepubertal male cortex. Progesterone and allopregnanolone levels decreased, and 3β-hydroxysteroid dehydrogenase 1 gene (Hsd3b1) expression was also downregulated in the prepubertal female cortex. Furthermore, cortisol levels increased, and mRNA expression of the nuclear receptor subfamily 3 group C member 1 gene (Nr3c1) was downregulated in the cortices of both sexes. Unlike the neonatal VPA-exposed models, although a decrease in progestin and estradiol levels was observed in females and males, respectively, no differences were observed in cortisol levels in the cortex tissues of 8-week-old adult rats administered VPA for four weeks. These results indicate that early environmental chemical exposure induces long-term neurosteroid metabolic effects in the brain, with differences according to sex.

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18. Kouznetsov R, Angelopoulos P, Moulinos S, Dimakos I, Gourzis P, Jelastopulu E. Epidemiological Study of Autism Spectrum Disorders in Greece for 2021: Nationwide Prevalence in 2-17-Year-Old Children and Regional Disparities. Journal of clinical medicine. 2023; 12(7).

This study estimated the crude prevalence of autism spectrum disorders (ASD) in Greece in 2021. A retrospective study was conducted for 2021 using data provided for research purposes for the first time by the Greek National Health Service Organization for Healthcare Services Provision (EOPYY) related to the ICD-10 diagnosis codes F84.0-F84.9 (ASD). Treatments were categorized by gender, age, and location. Statistical analysis was performed using the open-source software R. In total, 15,706 children aged 2-17 years were registered with ASD: 12,380 boys and 3326 girls. In total, 6,117,910 therapies were prescribed: 4,844,173 for boys and 1,273,737 for girls. Boys are estimated to be diagnosed 3.5 times more often than girls. On average, approximately 390 treatments are prescribed per person per year for both sexes. The annual prevalence is estimated at 0.94%, ranging from 0.42% to 1.44% depending on geographic region. Our findings provide evidence-based data for the planning of policies regarding health, education, and employment for people with ASD. The number of children and treatments makes ASD a public health concern to support children and their families and ensure equal participation in all aspects of society.

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19. Lockwood Estrin G, Bhavnani S, Arora R, Gulati S, Divan G. Caregiver Perceptions of Autism and Neurodevelopmental Disabilities in New Delhi, India. International journal of environmental research and public health. 2023; 20(7).

Evidence suggests that parenting an autistic child or a child with neurodevelopmental disabilities can be more challenging than parenting a child meeting their developmental milestones, especially when there is a dearth of support services, such as in low- and middle-income countries (LMICs). Despite the majority of the world’s children residing in LMICs, there are limited studies examining the understanding of developmental disorders and autism in these regions. We therefore aim to investigate perceptions of autism and developmental disabilities in caregivers of children in an urban setting in New Delhi, India. Thirteen semi-structured interviews with parents/caregivers of children were conducted in three groups: (1) caregivers with a child with a diagnosis of autism spectrum disorder (ASD); (2) caregivers with a child with a diagnosis of intellectual disability (ID); (3) and caregivers with children meeting their developmental milestones. Transcripts were analysed using framework analysis. Three themes on the impact of cultural and contextual factors on the recognition, interpretation, and reporting of autistic symptoms are discussed, and additional themes focus on the impact of diagnosis and family support. Our findings highlighted a vital need for greater community awareness and recognition of autism in India, for example through community and healthcare training, which may help to reduce stigma and facilitate wider family support.

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20. Meng F, Xuan B. Reliability and validity of the Chinese version of the Comprehensive Autistic Trait Inventory-short form (CATI-SF-C) in the general population. Asian journal of psychiatry. 2023; 84: 103580.

The current study aims to provide psychometric analyses of a shortened version of the Comprehensive Autistic Trait Inventory (CATI) from three different samples administered to 4910 Chinese populations (56.864 % females, mean age 19.857 ± 4.083) aged 14-56. The factor structure of CATI in Chinese was examined by confirmatory factor analysis and exploratory structural equation modeling, and a 24-item Chinese version short form of CATI (CATI-SF-C) was developed. The validity (structure validity, convergent validity, and discriminant validity) and reliability (internal consistency and test-retest reliability) were evaluated, and the predictive ability for classifying autism was examined (Youden’s Index = 0.690). According to these findings, the CATI-SF-C is a reliable and valid autistic traits assessment tool for the general population.

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21. Muller K. Exploring the Clinical Feasibility of Alternative Word-Understanding Measures for Autistic Children With Minimal Spoken Language. American journal of speech-language pathology. 2023: 1-14.

PURPOSE: The primary aim of this study was to explore the clinical feasibility of using alternate word-understanding assessment modalities for autistic children who have minimal verbal skills. Specifically, assessment duration, occurrence of disruptive behavior, and no-response trials were examined across three word-understanding assessment conditions: a low-tech condition, a touchscreen condition, and a condition that used real-object stimuli. A secondary aim was to examine the relationship between disruptive behavior and assessment outcomes. METHOD: Twenty-seven autistic children between the ages of 3 and 12 years who had minimal verbal skills completed 12 test items on the three assessment conditions. Repeated-measures analyses of variance with post hoc Bonferroni procedures were used to describe and compare assessment duration, occurrence of disruptive behavior, and no-response trials across conditions. A Spearman rank-order correlation coefficient was used to examine the relationship between disruptive behavior and assessment outcomes. RESULTS: The real-object assessment condition took significantly longer than the low-tech and touchscreen conditions. Participants engaged in disruptive behavior most frequently during the low-tech condition; however, differences among conditions were not significant. There were significantly more no-response trials in the low-tech condition than in the touchscreen condition. There was a significant, weak negative correlation between disruptive behavior and experimental assessment outcomes. CONCLUSION: Results show there is promise in using real objects and touchscreen devices to assess word understanding in autistic children who have minimal verbal skills.

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22. Murakami Y, Imamura Y, Kasahara Y, Yoshida C, Momono Y, Fang K, Sakai D, Konishi Y, Nishiyama T. Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder. Cells. 2023; 12(7).

Several studies show that genetic and environmental factors contribute to the onset and progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one of the major environmental factors driving this process. The kynurenine pathway (KP) is a major route of the essential amino acid L-tryptophan (Trp) catabolism in mammalian cells. Activation of the KP following neuro-inflammation can generate various endogenous neuroactive metabolites that may impact brain functions and behaviors. Additionally, neurotoxic metabolites and excitotoxicity cause long-term changes in the trophic support, glutamatergic system, and synaptic function following KP activation. Therefore, investigating the role of KP metabolites during neurodevelopment will likely promote further understanding of additional pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). In this review, we describe the changes in KP metabolism in the brain during pregnancy and represent how maternal inflammation and genetic factors influence the KP during development. We overview the patients with ASD clinical data and animal models designed to verify the role of perinatal KP elevation in long-lasting biochemical, neuropathological, and behavioral deficits later in life. Our review will help shed light on new therapeutic strategies and interventions targeting the KP for neurodevelopmental disorders.

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23. Osman HA, Haridi M, Gonzalez NA, Dayo SM, Fatima U, Sheikh A, Puvvada CS, Soomro FH, Khan S. A Systematic Review of the Efficacy of Early Initiation of Speech Therapy and Its Positive Impact on Autism Spectrum Disorder. Cureus. 2023; 15(3): e35930.

Autism spectrum disorder (ASD) is a condition that consists predominantly of an apparent early delay in communication and social skills. Among the multiple identified etiologies, genetics play a key role. The implementation of early interventional therapy for children with ASD is starting to show promising results. A few medical databases were used to collect multiple published types of research, which were thoroughly screened. Ultimately, a small amount was selected according to the defined eligibility criteria. The 12 articles that were reviewed involved a more significant number of boys than girls, and most clinical trials displayed the importance of starting early therapy. Astonishingly, the overwhelming effects of the COVID-19 pandemic did not affect the continuation of speech therapy in certain areas. In addition, studies emphasize knowledge scarcity, insufficient resources in certain areas, and the demand to educate the community. Conversely, no difference in the level of severity was noted with the implementation of early therapy. Early therapy, chiefly speech therapy used to treat children with ASD, demonstrated favorable outcomes. Communities require awareness about the condition on a broader scale to educate caregivers on early alarming symptoms. All in all, additional exploration needs to be done.

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24. Plunk A, Amat AZ, Tauseef M, Peters RA, Sarkar N. Semi-Supervised Behavior Labeling Using Multimodal Data during Virtual Teamwork-Based Collaborative Activities. Sensors (Basel, Switzerland). 2023; 23(7).

Adaptive human-computer systems require the recognition of human behavior states to provide real-time feedback to scaffold skill learning. These systems are being researched extensively for intervention and training in individuals with autism spectrum disorder (ASD). Autistic individuals are prone to social communication and behavioral differences that contribute to their high rate of unemployment. Teamwork training, which is beneficial for all people, can be a pivotal step in securing employment for these individuals. To broaden the reach of the training, virtual reality is a good option. However, adaptive virtual reality systems require real-time detection of behavior. Manual labeling of data is time-consuming and resource-intensive, making automated data annotation essential. In this paper, we propose a semi-supervised machine learning method to supplement manual data labeling of multimodal data in a collaborative virtual environment (CVE) used to train teamwork skills. With as little as 2.5% of the data manually labeled, the proposed semi-supervised learning model predicted labels for the remaining unlabeled data with an average accuracy of 81.3%, validating the use of semi-supervised learning to predict human behavior.

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25. Qu A, Duan B, Wang Y, Cui Z, Zhang N, Wu D. Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study. BMC pediatrics. 2023; 23(1): 174.

BACKGROUND: Several previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD. METHODS: A case-control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants’ fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared. RESULTS: The gut DNA virome in children aged 3-11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and β diversity did not differ statistically between groups. CONCLUSIONS: This study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.

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26. Rodrigues EL, Figueiredo PS, Marcelino G, de Cássia Avellaneda Guimarães R, Pott A, Santana LF, Hiane PA, do Nascimento VA, Bogo D, de Cássia Freitas K. Maternal Intake of Polyunsaturated Fatty Acids in Autism Spectrum Etiology and Its Relation to the Gut Microbiota: What Do We Know?. Nutrients. 2023; 15(7).

Maternal food habits and gut microbiota composition have potential effects on fetal neurodevelopment, impacting Autism Spectrum Disorder (ASD). Our research aims to outline the relationship that ingestion of polyunsaturated fatty acids (PUFAs) and the composition of maternal gut microbiota have with the possible development of ASD in offspring. We suggest that genetic factors could be related to the different conversions between unsaturated fatty acids according to sex and, mainly, the impact of the pregnancy diet on the higher or lower risk of neurological impairments. The proportion of the phyla Firmicutes/Bacteroidetes is high with an increased consumption of linoleic acid (LA, n-6 PUFA), which is associated with maternal intestinal dysbiosis and consequently starts the inflammatory process, harming myelinization. In contrast, the consumption of α-linolenic acid (ALA, n-3 PUFA) tends to re-establish the balance of the maternal microbiota with anti-inflammatory action. Moreover, human observational studies showed a strong correlation between the consumption of n-3 PUFA, mainly above 340 g of fish per week, with beneficial effects on infant neurodevelopment. Therefore, we suggest that the proper intake of foods rich in n-3 PUFAs and their supplementation during pregnancy until lactation has an impact on reducing the development of ASD. Controlled studies with n-3 PUFA supplementation are still necessary to verify the ideal dose and the best form of administration.

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27. Schwartzman JM, Muscatello RA, Corbett BA. Assessing suicidal thoughts and behaviors and nonsuicidal self-injury in autistic and non-autistic early adolescents using the Columbia Suicide Severity Rating Scale. Autism : the international journal of research and practice. 2023: 13623613231162154.

Autistic adolescents are more likely to experience suicidal thoughts and behaviors and nonsuicidal self-injury than non-autistic adolescents, per caregiver- and self-report on single-item questionnaires. Comprehensive, clinician-rated measures of suicide risk have not been used to measure suicidal thoughts and behaviors and nonsuicidal self-injury in autistic youth despite greater parent-child rating discrepancies among autistic youth than their non-autistic peers. The Columbia Suicide Severity Rating Scale is a widely used, clinician-rated measure of suicide risk that has not been tested with autistic youth. In this study, the Columbia Suicide Severity Rating Scale was employed to assess suicidal thoughts and behaviors and nonsuicidal self-injury in a community sample of 239 early adolescents (10:0-13:9 years old), of whom 138 youth were autistic and 101 were not autistic. Multiple analyses examined diagnostic (autistic vs non-autistic) and sex-based (male vs female) differences in suicidal thoughts and behaviors and nonsuicidal self-injury, as well as youth consistency in reporting across self- and clinician-rated measures. Findings show that a greater proportion of autistic youth reported lifetime suicidal thoughts and nonsuicidal self-injury than non-autistic youth; however, there were no sex-based differences. The majority of non-autistic youth were consistent in reporting suicidal thoughts on self- and clinician-rated measures; however, nearly one in five autistic youth disclosed suicidal thoughts on a self-report measure but not to a psychiatrist on the Columbia Suicide Severity Rating Scale. Findings suggest that autism diagnostic status, but not sex, confers significant risk for suicidal thoughts and behaviors and nonsuicidal self-injury in early adolescents and that the Columbia Suicide Severity Rating Scale may be a useful measure of suicide risk for some autistic youth, but it may not detect all autistic youth experiencing suicidal thoughts.

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28. Stancliffe RJ, Tichá R, Pettingell SL, Houseworth J, Bershadsky J. Current services and outcomes of formerly institutionalised and never-institutionalised US adults with intellectual and developmental disabilities: A propensity score matching analysis. Journal of applied research in intellectual disabilities : JARID. 2023.

BACKGROUND: Deinstitutionalization research shows better services and outcomes relative to institutional life but has not compared formerly institutionalised and never-institutionalised service users. METHODS: We used propensity score matching (PSM) to match formerly institutionalised and never-institutionalised participants on six personal characteristics. Data came from the 2018 to 2019 National Core Indicators In-Person Survey. We excluded current institution residents, and states with 25% + of missing data on former institutionalisation. RESULTS: Overall, 15.5% of participants in the 29-state full sample had lived in an institution for 1 year or more. Findings from the PSM sample showed that former-institution residents were more likely to use congregate living arrangements and less likely to live with family. They experienced more loneliness, less support-related choice, and had a consistent pattern of disability service-focused social connections. CONCLUSIONS: Many former institution residents remain disadvantaged relative to matched peers. There is a need to identify factors to enhance services and outcomes following deinstitutionalization.

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29. Tan WY, Hamzaid NH, Ibrahim N. Parental Perceptions on the Importance of Nutrients for Children with Autism Spectrum Disorder (ASD) and the Coping Strategies: A Qualitative Study. Nutrients. 2023; 15(7).

Autism Spectrum Disorder (ASD) is a developmental disorder that comes with co-occurring eating behavior such as limited food varieties, selective food intake, and repetitive eating patterns, contributing to significant challenges for their parents. Many parents find mealtimes difficult and develop anxiety or stress about their child’s nutrition, health, and overall well-being. Hence, parents must equip themselves with the correct awareness and nutrition knowledge. An online open-ended semi-structured interview was conducted among fifteen parents from the community-rehabilitation program center to explore their understanding of nutrition’s importance and the possible coping strategies when facing challenges. The interview sessions were recorded, followed by three researchers’ coding processes. Data were then subjected to thematic analysis. The interview sessions suggested that the parents were aware of the autism trait eating behavior and had a general knowledge about nutrition. However, it was quite challenging when it came to preparation. Nevertheless, the parents are able to manage the challenges with unique kinds of coping strategies. In addition, a complete educational dietary intervention program including psychosocial aspects for parents is recommended for better effectiveness.

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30. Valiyamattam GJ, Katti H, Chaganti VK, O’Haire ME, Sachdeva V. Circumscribed interests in autism: Can animals potentially re-engage social attention?. Research in developmental disabilities. 2023; 137: 104486.

BACKGROUND: Circumscribed interests (CI) in autism are highly fixated and repetitive interests, generally centering on non-social and idiosyncratic topics. The increased salience of CI objects often results in decreased social attention, thus interfering with social interactions. Behavioural, biomarker and neuroimaging research points to enhanced social functioning in autistic children in the presence of animals. For instance, neuroimaging studies report a greater activation of reward systems in the brain in response to animal stimuli whereas eye-tracking studies reveal a higher visual preference for animal faces in autistic individuals. This potentially greater social reward attached to animals, introduces the interesting and yet unexplored possibility that the presence of competing animal stimuli may reduce the disproportionately higher visual attention to CI objects. METHOD: We examined this using a paired-preference eye-tracking paradigm where images of human and animal faces were paired with CI and non-CI objects. 31 children (ASD n = 16; TD n = 15) participated in the study (3391 observations). RESULTS: Autistic children showed a significantly greater visual attention to CI objects whereas typical controls showed a significantly greater visual attention to social images across pairings. Interestingly, pairing with a CI object significantly reduced the social attention elicited to human faces but not animal faces. Further, in pairings with CI objects, significantly greater sustained attention per visit was seen for animal faces when compared to human faces. CONCLUSIONS: These results thus suggest that social attention deficits in ASD may not be uniform across human and animal stimuli. Animals may comprise a potentially important stimulus category modulating visual attention in ASD.

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31. Wang F, Memis I, Durocher JS, Furar E, Cavalcante L, Eshraghi RS, Samson AC, Van Herwegen J, Dukes D, Alessandri M, Mittal R, Eshraghi AA. Efficacy of coping mechanisms used during COVID-19 as reported by parents of children with autism. PloS one. 2023; 18(4): e0283494.

The COVID-19 pandemic’s alterations to daily life have been especially challenging for families with Autism Spectrum Disorder (ASD), worsening the core features of ASD and overall mental health. With the increased need for effective coping, the current retrospective study used data from a survey regarding parent reports of how often their child with ASD used certain coping strategies (frequency), as well as the extent to which they felt their child benefitted from their use (efficacy) in mitigating stress during the pandemic. This retrospective study Repeated measures ANOVAs were conducted to evaluate whether there were significant differences in both frequency and efficacy ratings for each coping strategy, for the entire sample as well as for three children’s age groups. Using Spearman’s rank-order correlations, correlation coefficients between the frequency and efficacy of each coping strategy were explored. Results revealed that maladaptive strategies were used more frequently than adaptive strategies, while parent routine as the most frequently used and efficacious for all age groups. Additionally, for adaptive strategies, humor and focusing on the positive had the strongest correlations between frequency and efficacy ratings amongst all age groups. Of the maladaptive strategies, repetitive behaviors, rumination, and isolation had the strongest correlations for the youngest, middle, and oldest age groups, respectively. Further, for each age group, the adaptive coping strategies had stronger correlations between frequency and efficacy than the maladaptive ones. It is our hope that the results of this study will lay the foundation for developing adaptive coping strategies to alleviate stress in children with ASD. Further investigations using a larger cohort are warranted to determine effective coping strategies for individuals with ASD across a range of situations, including acute stressors (such as future public health emergencies and natural disasters), as well as common daily stressors.

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32. Yamada K, Kimura T, Cui M, Tanaka E, Kubota Y, Ikehara S, Iso H. Maternal autistic traits and antenatal pain by cross-sectional analysis of the Japan Environment and Children’s Study. Scientific reports. 2023; 13(1): 6068.

The aim of cross-sectional study was to investigate whether the presence of autistic traits in pregnant women was positively associated with the prevalence and severity of antenatal pain. We analyzed 89,068 pregnant women from a Japanese national birth cohort cross-sectionally. Autistic traits were assessed using the Japanese version of the Autism-Spectrum Quotient short form (AQ-10-J). Antenatal pain was measured using the SF-8 bodily pain item (SF-8-Pain). Antenatal pain in the second to third trimester during pregnancy was categorized into three groups: without pain, mild pain, and moderate-to-severe pain. Participants were divided into eight groups by AQ-10-J score: seven consecutive scoring groups (scores 0-6), and those above the cut-off (≥ 7) for probable autistic spectrum disorders. Odds ratios (OR) for the prevalence of mild and moderate-to-severe pain were calculated for each AQ-10-J scoring group (reference: without pain group) using multinominal logistic regression analysis. Autistic traits were positively associated with mild and moderate-to-severe pain in a dose-response manner, but the association with moderate-to-severe pain was strongest. Fully-adjusted ORs (95% confidence intervals) for moderate-to-severe pain were: 1.01 (0.91-1.13) for 1 point, 1.13 (1.02-1.25) for 2 points, 1.16 (1.04-1.29) for 3 points, 1.20 (1.07-1.34) for 4 points, 1.23 (1.09-1.40) for 5 points, 1.27 (1.10-1.47) for 6 points, and 1.24 (1.05-1.46) for ≥ 7 points (AQ-10-J cut-off). We identified an association between maternal autistic traits and antenatal pain. Maternal autistic traits may need to be considered when addressing antenatal pain during healthcare for expectant mothers.

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