1. Bourke-Taylor HM, Joyce KS, Morgan P, Reddihough DS, Tirlea L. Maternal and child factors associated with the health-promoting behaviours of mothers of children with a developmental disability. Research in developmental disabilities. 2021; 118: 104069.

BACKGROUND/AIM: Mothers caring for their child or adult with a developmental disability can experience mental health disparity. Protective factors such as healthy behaviours are under-researched. This study investigated relationships between mental health, healthy behaviours, and disability factors. METHODS: The cross-sectional online survey included: Depression Anxiety Stress Scales (DASS); Family Empowerment Scale (FES); Health Promoting Activities Scale (HPAS); and a measure of childhood quality of life (QoL). RESULTS: All mothers were raising offspring (aged 3-36 years) with a developmental disability. Fifty-two percent of mothers (N = 81) had a mental health diagnosis. DASS scores were elevated for depression (58 %), anxiety (52 %) and stress (68 %). Mothers participated in health promoting activities infrequently and reported low satisfaction with community health-supporting facilities. Depressive symptoms, maternal empowerment and two indicators of child-related QoL explained 29.7 % of the variance in healthy behaviours. Depressive symptoms were the most important predictor of lack of health promoting behaviours. CONCLUSIONS: Better mental health predicted more frequent participation in health promoting behaviour. Future research might explore the extent to which health promoting behaviours protect mental health. Service changes including family health focused services, and custom designed health promotion or coaching programs may improve the health behaviours of mothers with high care responsibilities.

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2. Elsayed AK, Salloum-Asfar S, Abdulla SA. Human induced pluripotent stem cell line (QBRIi013-A) derivation from a 6-year-old female diagnosed with Autism spectrum disorder (ASD) and intellectual disability (ID). Stem cell research. 2021; 56: 102500.

Autism spectrum disorder (ASD) is a childhood-onset neurodevelopmental disorder characterized by social interaction, behavior, and communication challenges. Here, we generated an induced pluripotent stem cell (iPSC) line, QBRIi013-A using a non-integrating Sendai virus from a 6-year-old female diagnosed with ASD and intellectual disability. The QBRIi013-A cell line was fully characterized and exhibited a pluripotency capacity and trilineage differentiation potential. Furthermore, it showed normal karyotype and genetic identity to the patient’s PBMCs. Consequently, this iPSC line provides a valuable cell model in understanding the molecular mechanism underlying the complexities of ASD pathogenesis.

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3. Guo H, Jin ZL, Yao X, Park J, Gwon YP, Kim S, Kim KP, Cui XS, Kim NH, Yoo H, Han DW. Derivation of iPSC lines from two idiopathic ASD patients (OFi001-A, OFi002-A). Stem cell research. 2021; 56: 102510.

Here we described two human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD) patients through forced expression of OCT4, SOX2, KLF4, and c-MYC. The hiPSC lines displayed morphology, gene expression patterns, and pluripotential differentiation potentials similar to those of human embryonic stem cells (hESCs). The hiPSC lines from idiopathic ASD patients might be useful to unveil the underlying mechanism of idiopathic ASD and finding its therapeutics.

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4. Lawrence A. How Zoom helped the neurotypical world hear my autistic voice. Nature. 2021.

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5. Lindly OJ, Cabral J, Mohammed R, Garber I, Mistry KB, Kuhlthau KA. « I Don’t Do Much Without Researching Things Myself »: A Mixed Methods Study Exploring the Role of Parent Health Literacy in Autism Services Use for Young Children. Journal of autism and developmental disorders. 2021.

Little is known about how parent health literacy contributes to health-related outcomes for children with autism. This mixed-methods study included 82 U.S. parents of a child with autism 2-5 years-old and sought to describe (1) health literacy dimensions, (2) how health literacy influences services use, and (3) health literacy improvement strategies. Results showed: autism information was accessed from multiple sources; understanding autism information involved « doing your own research »; autism information empowered decision-making; health literacy facilitated behavioral services use; health literacy influenced medication use; family and system characteristics also affected services use; autism education remains needed; services information is needed across the diagnostic odyssey; and greater scientific information accessibility would increase uptake. Findings demonstrate how parent health literacy affects services use.

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6. McCrae CS, Mazurek MO, Curtis AF, Beversdorf DQ, Deroche CB, Golzy M, Sohl KA, Ner ZH, Davis BE, Stearns MA, Nair N. Protocol for targeting insomnia in school-aged children with autism spectrum disorder without intellectual disability: a randomised control trial. BMJ open. 2021; 11(8): e045944.

INTRODUCTION: Insomnia affects up to 80% of children with autism spectrum disorder (ASD). Negative consequences of insomnia in ASD include decreased quality of life (QOL), impaired learning and cognition, increased stereotypic and challenging behaviours, and increased parental stress. Cognitive behavioural treatment for childhood insomnia (CBT-CI) is a promising treatment for dealing with insomnia and its negative consequences but has not yet been studied in school-aged children with ASD and comorbid insomnia. Access to healthcare is another challenge for children with ASD, particularly in rural and underserved regions. Previous studies indicate that ASD and insomnia share common arousal-based underpinnings, and we hypothesise that CBT-CI will reduce the hyperarousal associated with insomnia and ASD. This trial will be the first to examine CBT-CI adapted for children with ASD and will provide new information about two different modes of delivery across a variety of primary and secondary child and parent sleep and related outcomes. Knowledge obtained from this trial might allow us to develop new or modify current treatments to better target childhood insomnia and ASD. METHODS AND ANALYSIS: Children (N=180) 6-12 years of age with ASD and insomnia will be recruited from an established autism database, a paediatric clinic and community outreach in the Columbia, MO and surrounding areas. Participants will be randomised to CBT-CI adapted for children with ASD (in-person or remote using computers with cameras) or Sleep Hygiene and Related Education. Participants will be assessed at baseline, post-treatment, 6-month and 12-month follow-ups. The following assessments will be completed regarding the children: objective and subjective sleep, daytime functioning (adaptive functioning, attention, challenging behaviours, anxiety), QOL and physiological arousal (heart rate variability) and parents: objective and subjective sleep, daytime functioning (anxiety, depression, fatigue), QOL, physiological arousal and parental burden/stress. ETHICS AND DISSEMINATION: Ethics approval was obtained in January 2020 from the University of Missouri. Ethics approval was obtained in July 2020 from the US Army Medical Research and Development Command, Office of Research Protections and Human Research Protection Office. All data are expected to be collected by 2024. Full trial results are planned to be published by 2025. Secondary analyses of baseline data will be subsequently published. TRIAL REGISTRATION NUMBER: NCT04545606; Pre-results.

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7. Reyes ST, Deacon RMJ, Guo SG, Altimiras FJ, Castillo JB, van der Wildt B, Morales AP, Park JH, Klamer D, Rosenberg J, Oberman LM, Rebowe N, Sprouse J, Missling CU, McCurdy CR, Cogram P, Kaufmann WE, Chin FT. Effects of the sigma-1 receptor agonist blarcamesine in a murine model of fragile X syndrome: neurobehavioral phenotypes and receptor occupancy. Scientific reports. 2021; 11(1): 17150.

Fragile X syndrome (FXS), a disorder of synaptic development and function, is the most prevalent genetic form of intellectual disability and autism spectrum disorder. FXS mouse models display clinically-relevant phenotypes, such as increased anxiety and hyperactivity. Despite their availability, so far advances in drug development have not yielded new treatments. Therefore, testing novel drugs that can ameliorate FXS’ cognitive and behavioral impairments is imperative. ANAVEX2-73 (blarcamesine) is a sigma-1 receptor (S1R) agonist with a strong safety record and preliminary efficacy evidence in patients with Alzheimer’s disease and Rett syndrome, other synaptic neurodegenerative and neurodevelopmental disorders. S1R’s role in calcium homeostasis and mitochondrial function, cellular functions related to synaptic function, makes blarcamesine a potential drug candidate for FXS. Administration of blarcamesine in 2-month-old FXS and wild type mice for 2 weeks led to normalization in two key neurobehavioral phenotypes: open field test (hyperactivity) and contextual fear conditioning (associative learning). Furthermore, there was improvement in marble-burying (anxiety, perseverative behavior). It also restored levels of BDNF, a converging point of many synaptic regulators, in the hippocampus. Positron emission tomography (PET) and ex vivo autoradiographic studies, using the highly selective S1R PET ligand [(18)F]FTC-146, demonstrated the drug’s dose-dependent receptor occupancy. Subsequent analyses also showed a wide but variable brain regional distribution of S1Rs, which was preserved in FXS mice. Altogether, these neurobehavioral, biochemical, and imaging data demonstrates doses that yield measurable receptor occupancy are effective for improving the synaptic and behavioral phenotype in FXS mice. The present findings support the viability of S1R as a therapeutic target in FXS, and the clinical potential of blarcamesine in FXS and other neurodevelopmental disorders.

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8. Schirwani S, Albaba S, Carere DA, Guillen Sacoto MJ, Milan Zamora F, Si Y, Rabin R, Pappas J, Renaud DL, Hauser N, Reid E, Blanchet P, Foulds N, Dixit A, Fisher R, Armstrong R, Isidor B, Cogne B, Schrier Vergano S, Demirdas S, Dykzeul N, Cohen JS, Grand K, Morel D, Slavotinek A, Albassam HF, Naik S, Dean J, Ragge N, Cinzia C, Tedesco MG, Harrison RE, Bouman A, Palen E, Challman TD, Willemsen MH, Vogt J, Cunniff C, Bergstrom K, Walia JS, Bruel AL, Kini U, Alkuraya FS, Slegesky V, Meeks N, Girotto P, Johnson D, Newbury-Ecob R, Ockeloen CW, Prontera P, Lynch SA, Li D, Graham JM, Jr., Balasubramanian M. Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3. American journal of medical genetics Part A. 2021; 185(11): 3446-58.

The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro-behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low-hanging columella. The presented data will inform clinical management of individuals with ASXL3-related syndrome and improve interpretation of new ASXL3 sequence variants.

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9. Sturm A, Huang S, Kuhfeld M. Advancing methodologies to improve RRB outcome measures in autism research: Evaluation of the RBS-R. Psychological assessment. 2022; 34(1): 30-42.

This study evaluates the psychometric properties (dimensionality, item bias, reliability) of the Repetitive Behavior Scale-Revised (RBS-R), provides scoring guidelines for the dimensional measure, and makes recommendations for future RRB measure development. Participants included individuals from three large autism data repositories; Simon Foundation Powering Autism Research for Knowledge (SPARK), Simons Simplex Collection (SSC), and National Database for Autism Research (NDAR). The total sample included N = 15,318 autistic individuals ages 3-18. Confirmatory factor analysis was used to evaluate competing theoretical factor structures. Item response theory (IRT) was used to evaluate differential item functioning, estimate the reliability of each RBS-R subdomain, and score the subdomains. A unidimensional factor structure demonstrated clearly inadequate model fit, calling into question the practice of reporting a total score on the RBS-R. A five-dimensional factor structure was supported by the theoretical and empirical evidence, though the fifth factor (restricted interests) was not sufficiently reliable for use. IRT-based scoring tools were generated for use in research. The present study illustrates the promise in the future development of measures for RRBs, particularly in the development of measures to separately and specifically assess RRB constructs using rigorous methodological guidelines. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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10. Sturrock A, Adams C, Freed J. A Subtle Profile With a Significant Impact: Language and Communication Difficulties for Autistic Females Without Intellectual Disability. Frontiers in psychology. 2021; 12: 621742.

The presentation of autism in females is poorly understood, which is thought to contribute to missed or later- age diagnosis, especially for those without intellectual disability. Dedicated research into social and behavioral differences has indicated a specific female phenotype of autism. However, less has been done to explore language and communication profiles, despite known sex/gender differences in typically developing populations. This article provides a synthesis of recent work from this small but emerging field. It focuses on a series of four preliminary and explorative studies conducted by the authors and embeds this within the wider literature. Findings suggest a specific profile of language and communication strengths and weaknesses for autistic females without intellectual disability (compared to autistic males and typically developing females). Furthermore, despite the relatively subtle presentation of difficulties (compared to autistic males), the impact on functionality, social inter-relations and emotional well-being, appears to be equitable and significant. The discussion highlights the need for further empirical research and proposes areas for investigation. Implications for clinical practice include the need for better recognition, testing and provision of interventions dedicated to the language and communication difficulties for autistic females. This has relevance for diagnostic, mental health and speech and language therapy services.

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11. Sun CK, Cheng YS, Hung KC. N-acetylcysteine is effective as add-on therapy to risperidone-based combination for children with autistic disorders. The Australian and New Zealand journal of psychiatry. 2022; 56(1): 91-2.

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12. Sun YJ, Xu LZ, Ma ZH, Yang YL, Yin TN, Gong XY, Gao ZL, Liu YL, Liu J. Health-related risky behaviors and their risk factors in adolescents with high-functioning autism. World journal of clinical cases. 2021; 9(22): 6329-42.

BACKGROUND: Health-related risky behaviors generally refer to behaviors that have a negative impact on health and quality of life. Health-related risky behaviors in adolescents with high-functioning autism (HFA) have not been well understood so far. Adolescents with HFA may have more health-related risky behaviors than neurotypical adolescents. AIM: To investigate health-related risky behaviors and their risk factors with HFA. METHODS: This is an observational study. Our study enrolled 110 adolescents aged 12-19-years-old meeting Diagnostic and Statistical Manual of Mental Disorders 4(th) edition criteria for HFA. They were recruited from Peking University Sixth Hospital. There were also 110 age, sex and nationality matched controls enrolled who came from a public school in Beijing, China. Both groups completed the Adolescents Health-related Risky Behavior Inventory. Nonparametric tests were carried out for comparison of the Adolescents Health-related Risky Behavior Inventory scores between the two groups. Expression recognition, the Inventory of Subjective Life Quality for Child and Adolescent, Chinese Wechsler Intelligence Scale for Children, Wechsler Intelligence Scale for Adult-Chinese Revised, Theory of Mind test and Autism Spectrum Screening Questionnaire were assessed in the autism group to explore factors associated with health-related risky behaviors. Multivariate regression analysis was conducted to explore the risk factors of health-related risky behaviors in the HFA group. RESULTS: The results showed that the total score of the Adolescents Health-related Risky Behavior Inventory and scores of « aggression and violence, » « suicide and self-injury, » « health compromising behavior » and « unprotected sex » subscales in the HFA group were significantly higher than those in the control group (Z range -4.197 to -2.213, P < 0.05). Among the associated factors, poor emotional experience (B = -0.268, P < 0.001), depression (B = -0.321, P < 0.001), low score of intelligence (B = -0.032, P = 0.042), low score of Theory of Mind test (B = -1.321, P = 0.003) and poor adaptation to school life (B = -0.152, P = 0.006) were risk factors. These risky behaviors may promote the occurrence of health-related risky behaviors in adolescents with HFA. CONCLUSION: This study showed that adolescents with HFA were more likely to be involved in health-related risky behaviors. Different health-related risky behaviors have different reasons.

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13. Urresti J, Zhang P, Moran-Losada P, Yu NK, Negraes PD, Trujillo CA, Antaki D, Amar M, Chau K, Pramod AB, Diedrich J, Tejwani L, Romero S, Sebat J, Yates Iii JR, Muotri AR, Iakoucheva LM. Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism. Molecular psychiatry. 2021; 26(12): 7560-80.

Reciprocal deletion and duplication of the 16p11.2 region is the most common copy number variation (CNV) associated with autism spectrum disorders. We generated cortical organoids from skin fibroblasts of patients with 16p11.2 CNV to investigate impacted neurodevelopmental processes. We show that organoid size recapitulates macrocephaly and microcephaly phenotypes observed in the patients with 16p11.2 deletions and duplications. The CNV dosage affects neuronal maturation, proliferation, and synapse number, in addition to its effect on organoid size. We demonstrate that 16p11.2 CNV alters the ratio of neurons to neural progenitors in organoids during early neurogenesis, with a significant excess of neurons and depletion of neural progenitors observed in deletions. Transcriptomic and proteomic profiling revealed multiple pathways dysregulated by the 16p11.2 CNV, including neuron migration, actin cytoskeleton, ion channel activity, synaptic-related functions, and Wnt signaling. The level of the active form of small GTPase RhoA was increased in both, deletions and duplications. Inhibition of RhoA activity rescued migration deficits, but not neurite outgrowth. This study provides insights into potential neurobiological mechanisms behind the 16p11.2 CNV during neocortical development.

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14. Zhao Z, Tang H, Zhang X, Qu X, Hu X, Lu J. Classification of Children With Autism and Typical Development Using Eye-Tracking Data From Face-to-Face Conversations: Machine Learning Model Development and Performance Evaluation. Journal of medical Internet research. 2021; 23(8): e29328.

BACKGROUND: Previous studies have shown promising results in identifying individuals with autism spectrum disorder (ASD) by applying machine learning (ML) to eye-tracking data collected while participants viewed varying images (ie, pictures, videos, and web pages). Although gaze behavior is known to differ between face-to-face interaction and image-viewing tasks, no study has investigated whether eye-tracking data from face-to-face conversations can also accurately identify individuals with ASD. OBJECTIVE: The objective of this study was to examine whether eye-tracking data from face-to-face conversations could classify children with ASD and typical development (TD). We further investigated whether combining features on visual fixation and length of conversation would achieve better classification performance. METHODS: Eye tracking was performed on children with ASD and TD while they were engaged in face-to-face conversations (including 4 conversational sessions) with an interviewer. By implementing forward feature selection, four ML classifiers were used to determine the maximum classification accuracy and the corresponding features: support vector machine (SVM), linear discriminant analysis, decision tree, and random forest. RESULTS: A maximum classification accuracy of 92.31% was achieved with the SVM classifier by combining features on both visual fixation and session length. The classification accuracy of combined features was higher than that obtained using visual fixation features (maximum classification accuracy 84.62%) or session length (maximum classification accuracy 84.62%) alone. CONCLUSIONS: Eye-tracking data from face-to-face conversations could accurately classify children with ASD and TD, suggesting that ASD might be objectively screened in everyday social interactions. However, these results will need to be validated with a larger sample of individuals with ASD (varying in severity and balanced sex ratio) using data collected from different modalities (eg, eye tracking, kinematic, electroencephalogram, and neuroimaging). In addition, individuals with other clinical conditions (eg, developmental delay and attention deficit hyperactivity disorder) should be included in similar ML studies for detecting ASD.

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