1. A MM, M AH, Aboulghate A, Abu-Mandil Hassan N, W SM, A SI, S MES, N HA, H BM, M HM, G AE, Elsaied A, E AA, A SE, Abdelhady S, S EE, M ME-S, S AE-M, N EH, H YB, N AE, Abdelrahman M, K MA. The odds of having obesity in Egyptian children with autism spectrum disorders is higher than stunting compared to healthy developing peers: a national survey. BMC Pediatr;2024 (Jul 20);24(1):465.

BACKGROUND: The nutritional status and growth of children with Autism spectrum disorders (ASD) is influenced significantly by two factors; food selectivity behaviors due to their consumption of a limited variety of food and the high incidence of gastrointestinal (GIT) disorders. AIM: This study aimed to assess the nutritional adequacy and growth pattern of ASD children aged three to twelve years compared to their healthy developing peers. METHODS: A national comparative, facility-based cross-sectional study was conducted in eight Egyptian governorates on 285 Egyptian children diagnosed with ASD and 224 children who are their relatives as healthy developing peers. Anthropometric measurements were obtained, including weight, height, head circumference, and mid-upper arm circumference. Body Mass Index (BMI) was calculated and all numbers were plotted on WHO growth charts. Assessment of food preferences, and nutrient intake adequacy of children was done using the Food preference questionnaire, and the Dietary Reference Intakes (DRIs) of Egyptian children. RESULTS: Calorie-dense food and sugar intake were higher among ASD children than their healthy developing peers. ASD children omit some important protein sources such as dairy (COR = 5.2, 95% CI:2.7-9.9), meat, and poultry (COR = 2.7, 95% CI: 1.6-4.7), and a lower intake of fruits and vegetables than their healthy developing peers. For children with ASD in all age groups, a deficiency in the range of 50-60% was detected for vitamins (C, D, B6, thiamine, riboflavin, niacin) and minerals (iron). A deficiency in the range of 60-70% was detected for folate and calcium. A deficiency of vitamin C calcium and iron was also detected for both children with ASD and their healthy developing relatives aged 6 to 12 years. GIT disorders were common among ASD children compared to healthy developing peers (COR = 2.8 to 10.3). Children with ASD had four-fold higher odds of stunting (COR = 4.1, CI: 1.7-10.1), threefold higher odds of being overweight (COR = 3.3, CI: 1.48-7.32), and nearly eleven-fold higher odds of obesity (COR = 11.4, CI: 4.05-32.17) compared to their healthy developing peers. CONCLUSION: ASD children are prone to overweight and protein malnutrition. Their intake of fruits and vegetables is inadequate and hence their intake of vitamins and minerals is insufficient, contributing to stunting.

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2. Hu C, Yang T, Chen J, Dai Y, Wei H, Wu Q, Chen H, Long D, Feng Y, Wei Q, Zhang Q, Chen L, Li T. Phenotypic characteristics and rehabilitation effect of children with regressive autism spectrum disorder: a prospective cohort study. BMC Psychiatry;2024 (Jul 19);24(1):514.

BACKGROUND: In this prospective cohort study, we determined the phenotypic characteristics of children with regressive autism spectrum disorder (ASD) and explored the effects of rehabilitation. METHODS: We recruited 370 children with ASD aged 1.5-7 years. Based on the Regression Supplement Form, the children were assigned to two groups: regressive and non-regressive. The core symptoms and neurodevelopmental levels of ASD were assessed before and after 1 year of behavioral intervention using the Autism Diagnostic Observation Schedule (ADOS), Social Response Scale (SRS), Children Autism Rating Scale (CARS), and Gesell Developmental Scale (GDS). RESULTS: Among the 370 children with ASD, 28.38% (105/370) experienced regression. Regression was primarily observed in social communication and language skills. Children with regressive ASD exhibited higher SRS and CARS scores and lower GDS scores than those with non-regressive ASD. After 1 year of behavioral intervention, the symptom scale scores significantly decreased for all children with ASD; however, a lesser degree of improvement was observed in children with regressive ASD than in those with non-regressive ASD. In addition, the symptom scores of children with regressive ASD below 4 years old significantly decreased, whereas the scores of those over 4 years old did not significantly improve. Children with regressive ASD showed higher core symptom scores and lower neurodevelopmental levels. Nevertheless, after behavioral intervention, some symptoms exhibited significant improvements in children with regressive ASD under 4 years of age. CONCLUSION: Early intervention should be considered for children with ASD, particularly for those with regressive ASD.

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3. Hull L, Stark I, Lundberg M, Ahlqvist VH, Nordström SI, Ohlis A, Hadlaczky G, Rai D, Magnusson C. Sex differences in self-harm and suicide in young autistic adults. Acta Psychiatr Scand;2024 (Jul 19)

INTRODUCTION: Both suicide and self-harm are disproportionately common in autistic people. Sex differences in risk of self-harm and suicide are observed in the general population, but findings are mixed for autistic people. Self-cutting may be a particularly risky self-harm behaviour for suicide in autistic people. We aimed to explore sex differences and differences in method of self-harm in the association between self-harm and suicide in autistic and non-autistic adolescents and young adults. METHODS: We used a total population register of 2.8 million Swedish residents. Participants were followed from age 12 until December 2021 for medical treatment because of self-harm, and death from suicide. We used Cox proportional hazard regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of death from suicide following self-harm, and Relative Excessive Risk due to Interaction (RERI) to explore the interaction between self-harm and autism in females and males. RESULTS: We identified 85,143 autistic individuals (31,288 female; 53,855 male) and 2,628,382 non-autistic individuals (1,286,481 female; 1,341,901 male) aged 12-37 years. Incidence of suicide following self-harm was higher in autistic males (incidence per 100,000 risk-years = 169.0 [95% CI 135.1, 211.3]) than females (125.4 [99.4, 158.3]). The relative risk was higher for autistic females (HR 26.1 [95% CI 20.2, 33.7]) than autistic males (12.5 [9.9, 15.8]). An additive effect of both autism and self-harm was observed in both females (RERI = 9.8) and males (2.0). Autistic individuals who self-harmed through cutting were at greatest risk of death from suicide (HR 25.1 [17.9, 35.2]), compared to other methods. CONCLUSION: Autistic males and females are at increased risk of death from suicide following severe self-harm, particularly self-cutting.

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4. Ouellette J, Lacoste B. Rock2 heterozygosity improves recognition memory and endothelial function in a mouse model of 16p11.2 deletion autism syndrome. Neurosci Lett;2024 (Jul 17):137904.

Rho-associated protein kinase-2 (ROCK2) is a critical player in many cellular processes and was incriminated in cardiovascular and neurological disorders. Recent evidence has shown that non-selective pharmacological blockage of ROCKs ameliorates behavioral alterations in a mouse model of 16p11.2 haploinsufficiency. We had revealed that 16p11.2-deficient mice also display cerebrovascular abnormalities, including endothelial dysfunction. To investigate whether genetic blockage of ROCK2 also exerts beneficial effects on cognition and angiogenesis, we generated mice with both 16p11.2 and Rock2 haploinsufficiency (16p11.2(df/+);Rock2(+/-)). We find that Rock2 heterozygosity on a 16p11.2(df/+) background significantly improved recognition memory. Furthermore, brain endothelial cells from 16p11.2(df/+);Rock2(+/-) mice display improved angiogenic capacity compared to cells from 16p11.2(df/+) littermates. Overall, this study implicates Rock2 gene as a modulator of 16p11.2-associated alterations, highlighting its potential as a target for treatment of autism spectrum disorders.

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5. Pedrazzi JFC, Hassib L, Ferreira FR, Hallak JC, Del-Bel E, Crippa JA. Therapeutic potential of CBD in Autism Spectrum Disorder. Int Rev Neurobiol;2024;177:149-203.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior. Despite extensive research, effective pharmacological interventions for ASD remain limited. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has potential therapeutic effects on several neurological and psychiatric disorders. CBD interacts with the endocannabinoid system, a complex cell-signaling system that plays a crucial role in regulating various physiological processes, maintaining homeostasis, participating in social and behavioral processing, and neuronal development and maturation with great relevance to ASD. Furthermore, preliminary findings from clinical trials indicate that CBD may have a modulatory effect on specific ASD symptoms and comorbidities in humans. Interestingly, emerging evidence suggests that CBD may influence the gut microbiota, with implications for the bidirectional communication between the gut and the central nervous system. CBD is a safe drug with low induction of side effects. As it has a multi-target pharmacological profile, it becomes a candidate compound for treating the central symptoms and comorbidities of ASD.

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6. Peters SU, Shelton AR, Malow BA, Neul JL. A clinical-translational review of sleep problems in neurodevelopmental disabilities. J Neurodev Disord;2024 (Jul 20);16(1):41.

Sleep disorders are very common across neurodevelopmental disorders and place a large burden on affected children, adolescents, and their families. Sleep disturbances seem to involve a complex interplay of genetic, neurobiological, and medical/environmental factors in neurodevelopmental disorders. In this review, we discuss animal models of sleep problems and characterize their presence in two single gene disorders, Rett Syndrome, and Angelman Syndrome and two more commonly occurring neurodevelopmental disorders, Down Syndrome, and autism spectrum disorders. We then discuss strategies for novel methods of assessment using wearable sensors more broadly for neurodevelopmental disorders in general, including the importance of analytical validation. An increased understanding of the mechanistic contributions and potential biomarkers of disordered sleep may offer quantifiable targets for interventions that improve overall quality of life for affected individuals and their families.

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7. Postma JK, Harrison MA, Kutcher S, Webster RJ, Cloutier M, Bourque DK, Yu AC, Carter MT. The diagnostic yield of genetic and metabolic investigations in syndromic and nonsyndromic patients with autism spectrum disorder, global developmental delay, or intellectual disability from a dedicated neurodevelopmental disorders genetics clinic. Am J Med Genet A;2024 (Jun 20):e63791.

First-tier genetic investigations for patients with neurodevelopmental disorders (NDDs) may include chromosomal microarray, Fragile X testing, and screening for inherited metabolic diseases, but most remain undiagnosed upon completion of testing. Here, we report the diagnostic yields of genetic testing for 537 patients with at least one of autism spectrum disorder, global developmental delay, and/or intellectual disability. Patients were assessed in a single neurodevelopmental genetics clinic, and each underwent a standardized history and physical examination. Each patient was characterized as syndromic or nonsyndromic based on clinical features. Our results demonstrate that multigene sequencing (with an NDD gene panel or exome) had a higher diagnostic yield (8%; 95% confidence interval [CI]: 5%, 13%) than chromosomal microarray and Fragile X testing combined (4%; 95% CI: 3%, 7%). Biochemical screening for inherited metabolic diseases had a diagnostic yield of zero. The diagnostic yield of genetic testing was significantly higher for syndromic patients than for nonsyndromic patients (odds ratio [OR] 3.09; 95% CI: 1.46, 6.83) and higher for female patients than for male (OR 3.21; 95% CI: 1.52, 6.82). These results add to the growing evidence supporting a comprehensive genetic evaluation that includes both copy number analysis and sequencing of known NDD genes for patients with NDDs.

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8. Radhakrishnan M, Ramamurthy K, Shanmugam S, Prasanna G, S V, Y S, Won D. A hybrid model for the classification of Autism Spectrum Disorder using Mu rhythm in EEG. Technol Health Care;2024 (Jul 15)

BACKGROUND: Autism Spectrum Disorder (ASD) is a condition with social interaction, communication, and behavioral difficulties. Diagnostic methods mostly rely on subjective evaluations and can lack objectivity. In this research Machine learning (ML) and deep learning (DL) techniques are used to enhance ASD classification. OBJECTIVE: This study focuses on improving ASD and TD classification accuracy with a minimal number of EEG channels. ML and DL models are used with EEG data, including Mu Rhythm from the Sensory Motor Cortex (SMC) for classification. METHODS: Non-linear features in time and frequency domains are extracted and ML models are applied for classification. The EEG 1D data is transformed into images using Independent Component Analysis-Second Order Blind Identification (ICA-SOBI), Spectrogram, and Continuous Wavelet Transform (CWT). RESULTS: Stacking Classifier employed with non-linear features yields precision, recall, F1-score, and accuracy rates of 78%, 79%, 78%, and 78% respectively. Including entropy and fuzzy entropy features further improves accuracy to 81.4%. In addition, DL models, employing SOBI, CWT, and spectrogram plots, achieve precision, recall, F1-score, and accuracy of 75%, 75%, 74%, and 75% respectively. The hybrid model, which combined deep learning features from spectrogram and CWT with machine learning, exhibits prominent improvement, attained precision, recall, F1-score, and accuracy of 94%, 94%, 94%, and 94% respectively. Incorporating entropy and fuzzy entropy features further improved the accuracy to 96.9%. CONCLUSIONS: This study underscores the potential of ML and DL techniques in improving the classification of ASD and TD individuals, particularly when utilizing a minimal set of EEG channels.

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9. Serrano M, Elias M, Llorens M, Bolasell M, Vall-Roqué H, Villalta L. Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial. Trials;2024 (Jul 20);25(1):496.

BACKGROUND: Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents’ mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children’s mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children’s developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients. METHODS: We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists. DISCUSSION: Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06125093 . Date of registration: first submitted 2023-10-23; first posted 2023-11-09. URL of trial registry record.

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10. Sterrett K, Clarke E, Nofer J, Piven J, Lord C. Toward a functional classification for autism in adulthood. Autism Res;2024 (Jul 19)

Autism spectrum disorder (ASD) is a heterogeneous condition that affects development and functioning from infancy through adulthood. Efforts to parse the heterogeneity of the autism spectrum through subgroups such as Asperger’s and Profound Autism have been controversial, and have consistently struggled with issues of reliability, validity, and interpretability. Nonetheless, methods for successfully identifying clinically meaningful subgroups within autism are needed to ensure that research, interventions, and services address the range of needs experienced by autistic individuals. The purpose of this study was to generate and test whether a simple set of questions, organized in a flowchart, could be used in clinical practice and research to differentiate meaningful subgroups based on individuals’ level of functioning. Once generated, subgroups could also be compared to the recently proposed administrative category of Profound Autism and to groupings based on standardized adaptive measures. Ninety-seven adults with autism or related neurodevelopmental disorders participating in a longstanding longitudinal study, or their caregivers if they could not answer for themselves, completed phone interviews when the participants were ~30 years old. Information from these phone interviews was used to generate vignettes summarizing characteristics and aspects of the daily lives of each participant (e.g., language level, vocational activities, and social relationships). Three expert clinicians then used these vignettes to classify each participant based on their level of support needs. Meaningfully distinct subgroups within the sample were identified which could be reliably distinguished from one another. Implications of such categorizations and future directions are discussed.

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11. Uglik-Marucha N, Mason D, Belcher H, Happé F, Vitoratou S. Protocol for a systematic review evaluating psychometric properties and gender-related measurement (non)invariance of self-report assessment tools for autism in adults. Syst Rev;2024 (Jul 19);13(1):188.

BACKGROUND: Given the recent evidence on gender differences in the presentation of autism, there is an increasing concern that current tools for autism do not adequately capture traits more often found in women. If tools for autism measure autistic traits differently based on gender alone, their validity may be compromised as they may not be measuring the same construct across genders. Measurement invariance investigations of autism measures can help assess the validity of autism constructs for different genders. The aim of this systematic review is to identify and critically appraise the psychometric properties of all self-report tools for autism in adults that meet two criteria: (a) they have been published since or included in the NICE (2014) recommendations, and (b) they have undergone gender-related measurement invariance investigations as part of their validation process. METHODS: A search of electronic databases will be conducted from 2014 until the present using MEDLINE, Embase, and PsycINFO using predefined search terms to identify eligible studies. The search for grey literature will include sources such as OpenGrey, APA PsycEXTRA, and Scopus. Two reviewers will independently screen titles, abstracts, and full texts for eligibility. The references of included studies will be searched for additional records. The methodological quality of the studies will be evaluated using the COSMIN Risk of Bias checklist, while psychometric quality of findings will be assessed based on criteria for good measurement properties and ConPsy checklist. The quality of the total body of evidence will be appraised using the approach outlined in the modified GRADE guidelines. DISCUSSION: This systematic review will be among the first to assess the psychometric properties and gender-related measurement invariance of self-reported measures for autism in adults that were published since (or included in) NICE (2014) guidelines. The review will provide recommendations for the most suitable tool to assess for autism without gender bias. If no such measure is found, it will identify existing tools with promising psychometric properties that require further testing, or suggest developing a new measure. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42023429350.

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12. Wawer A, Chojnicka I, Sarzyńska-Wawer J, Krawczyk M. A cross-dataset study on automatic detection of autism spectrum disorder from text data. Acta Psychiatr Scand;2024 (Jul 20)

OBJECTIVE: The goals of this article are as follows. First, to investigate the possibility of detecting autism spectrum disorder (ASD) from text data using the latest generation of machine learning tools. Second, to compare model performance on two datasets of transcribed statements, collected using two different diagnostic tools. Third, to investigate the feasibility of knowledge transfer between models trained on both datasets and check if data augmentation can help alleviate the problem of a small number of observations. METHOD: We explore two techniques to detect ASD. The first one is based on fine-tuning HerBERT, a BERT-based, monolingual deep transformer neural network. The second one uses the newest, multipurpose text embeddings from OpenAI and a classifier. We apply the methods to two separate datasets of transcribed statements, collected using two different diagnostic tools: thought, language, and communication (TLC) and autism diagnosis observation schedule-2 (ADOS-2). We conducted several cross-dataset experiments in both a zero-shot setting and a setting where models are pretrained on one dataset and then training continues on another to test the possibility of knowledge transfer. RESULTS: Unlike previous studies, the models we tested obtained average results on ADOS-2 data but reached very good performance of the models in TLC. We did not observe any benefits from knowledge transfer between datasets. We observed relatively poor performance of models trained on augmented data and hypothesize that data augmentation by back translation obfuscates autism-specific signals. CONCLUSION: The quality of machine learning models that detect ASD from text data is improving, but model results are dependent on the type of input data or diagnostic tool.

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13. Yan Z. Targeting epigenetic enzymes for autism treatment. Trends Pharmacol Sci;2024 (Jul 20)

Emerging preclinical autism research has shown the therapeutic promise of pharmacological inhibitors for epigenetic enzymes, such as histone deacetylases (HDAC), euchromatic histone methyltransferases (EHMT), and lysine-specific histone demethylase 1A (LSD1). These interventions restore gene expression, synaptic function, and behavioral performance in autism models, highlighting a new strategy for autism treatment.

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14. Yazdani A, Samms-Vaughan M, Saroukhani S, Bressler J, Hessabi M, Tahanan A, Grove ML, Gangnus T, Putluri V, Kamal AHM, Putluri N, Loveland KA, Rahbar MH. Metabolomic Profiles in Jamaican Children With and Without Autism Spectrum Disorder. J Autism Dev Disord;2024 (Jul 20)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, metabolic perturbations associated with ASD, which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls in order to identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, an age and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and missing data imputation, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child’s parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. The amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

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15. Zhang Y, Delahanty MT, Engel SM, Marshall S, O’Shea TM, Garcia T, Schieve LA, Bradley C, Daniels JL. Malpresentation and autism spectrum disorder in the study to explore early development. Paediatr Perinat Epidemiol;2024 (Jun 21)

BACKGROUND: An infant’s presentation at delivery may be an early indicator of developmental differences. Non-vertex presentation (malpresentation) complicates delivery and often leads to caesarean section, which has been associated with neurodevelopmental delays, including autism spectrum disorder (ASD). However, malpresentation could be an early sign of an existing developmental problem that is also an upstream factor from caesarean delivery. Little research has been done to investigate the association between malpresentation and ASD. OBJECTIVES: We examine the association between malpresentation at delivery and ASD and whether this association differs by gestational age. METHODS: We used data from the Study to Explore Early Development (SEED), a multi-site, case-control study of children with ASD compared to population controls. The foetal presentation was determined using medical records, birth records and maternal interviews. We defined malpresentation as a non-vertex presentation at delivery, then further categorised into breech and other malpresentation. We used multivariable logistic regression to estimate the adjusted odds ratio (aOR) for the association between malpresentation and ASD. RESULTS: We included 4047 SEED participants, 1873 children with ASD and 2174 controls. At delivery, most infants presented vertex (n = 3760, 92.9%). Malpresentation was associated with higher odds of ASD (aOR 1.31, 95% confidence interval [CI] 1.02, 1.68) after adjustment for maternal age, poverty level, hypertensive disorder and smoking. The association was similar for breech and other types of malpresentation (aOR 1.28, 95% CI 0.97, 1.70 and aOR 1.40, 95% CI 0.87, 2.26, respectively) and did not differ markedly by gestational age. CONCLUSIONS: Malpresentation at delivery was modestly associated with ASD. Early monitoring of the neurodevelopment of children born with malpresentation could identify children with ASD sooner and enhance opportunities to provide support to optimise developmental outcomes.

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