1. Akkus N, Cubuk PO. Diagnostic yield of the chromosomal microarray analysis in turkish patients with unexplained development delay/ıntellectual disability(ID), autism spectrum disorders and/or multiple congenital anomalies and new clinical findings. Mol Biol Rep. 2024; 51(1): 577.

BACKGROUND: Chromosomal microarray analysis is an essential tool for copy number variants detection in patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, and multiple congenital anomalies. The study aims to determine the clinical significance of chromosomal microarray analysis in this patient group. Another crucial aspect is the evaluation of copy number variants detected in terms of the diagnosis of patients. METHODS AND RESULTS: A Chromosomal microarray analysis was was conducted on a total of 1227 patients and phenotype-associated etiological diagnosis was established in 135 patients. Phenotype-associated copy number variants were detected in 11% of patients. Among these, 77 patients 77 (57%, 77/135) were diagnosed with well-recognized genetic syndromes and phenotype-associated copy number variants were found in 58 patients (42.9%, 58/135). The study was designed to collect data of patients in Kocaeli Derince Training and Research Hospital retrospectively. In our study, we examined 135 cases with clinically significant copy number variability among all patients. CONCLUSIONS: In this study, chromosomal microarray analysis revealed pathogenic de novo copy number variants with new clinical features. Chromosomal microarray analysis in the Turkish population has been reported in the largest patient cohort to date.

Lien vers le texte intégral (Open Access ou abonnement)

2. Ambarchi Z, Boulton KA, Thapa R, Arciuli J, DeMayo MM, Hickie IB, Thomas EE, Guastella AJ. Social and joint attention during shared book reading in young autistic children: a potential marker for social development. J Child Psychol Psychiatry. 2024.

BACKGROUND: Atypical patterns of social engagement and joint attention behaviors are diagnostic criteria for people with autism spectrum disorder. Experimental tasks using eye-tracking methodologies have, however, shown inconsistent results. The development of tasks with greater ecological validity and relevance for developmentally appropriate social milestones has been identified as important for the field. METHODS: We developed a novel, dynamic eye-tracking task emulating a shared book reading (SBR) scenario. Four SBR videos of an adult reader engaging with the viewer while reading a children’s picture book and including sequenced bids for joint attention were developed. Participants included 90 children (N = 56 autistic children, N = 34 neurotypical children; aged 3-12). Social attention was also measured in a live free play task between participants and an experimenter. RESULTS: Compared to neurotypical children, autistic children displayed reduced attention to socially salient stimuli including the reader’s face and picture book across SBR videos and during joint attention bids specifically. In contrast, they showed increased attention to nonsalient background stimuli compared to their neurotypical peers. These attention patterns in autistic children were associated with reduced verbal and nonverbal cognitive skills and increased symptoms associated with autism. Interestingly, positive correlations in the frequency of eye gaze between SBR and free play suggested a potential predictive value for social attention in live social interactions. CONCLUSIONS: Findings highlight the utility of SBR eye-tracking tasks in understanding underlying divergences in social engagement and joint attention between autistic and neurotypical children. This commonly practiced early childhood activity may provide insights into the relationship between social engagement and learning to reveal how such attentional patterns might influence broader developmental and educational outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

3. Arias V, Esteban L, Navas P, Verdugo M. Improving Quality of Life and Reducing Behavioral Problems of People With Intellectual and Developmental Disabilities Through Deinstitutionalization. Psicothema. 2023; 36(2): 113-22.

ANTECEDENTS: People with intellectual and developmental disability (IDD) with extensive support needs are more likely to live in segregated and highly institutionalized environments. The aim of this study was to analyze changes in functioning and quality of life for people with IDD and extensive support needs after transitioning to ordinary homes in the community. METHOD: The sample included 54 adults with IDD and extensive support needs, who were assessed at three time points: before transition, six months later, and one year after transition. The Resident Choice Scale, San Martin Quality of Life Scale, Active Support Participation Measure, and the Behavior Problem section of the Inventory for Client and Agency Planning were administered. Partial least squares-structural equation modeling (PLS-SEM) and t-tests for repeated measures were carried out. RESULTS: There were significant improvements in decision-making, participation and independence in daily activities and quality of life, as well as a reduction in the presence and intensity of behavioral problems. CONCLUSIONS: The benefits found in this study support transformation processes towards more inclusive services and professional practices that foster people’s rights and feeling of belonging to the community.

Lien vers le texte intégral (Open Access ou abonnement)

4. Bae HG, Wu WC, Nip K, Gould E, Kim JH. Scn2a deletion disrupts oligodendroglia function: Implication for myelination, neural circuitry, and auditory hypersensitivity in ASD. bioRxiv. 2024.

Autism spectrum disorder (ASD) is characterized by a complex etiology, with genetic determinants significantly influencing its manifestation. Among these, the Scn2a gene emerges as a pivotal player, crucially involved in both glial and neuronal functionality. This study elucidates the underexplored roles of Scn2a in oligodendrocytes, and its subsequent impact on myelination and auditory neural processes. The results reveal a nuanced interplay between oligodendrocytes and axons, where Scn2a deletion causes alterations in the intricate process of myelination. This disruption, in turn, instigates changes in axonal properties and neuronal activities at the single cell level. Furthermore, oligodendrocyte-specific Scn2a deletion compromises the integrity of neural circuitry within auditory pathways, leading to auditory hypersensitivity-a common sensory abnormality observed in ASD. Through transcriptional profiling, we identified alterations in the expression of myelin-associated genes, highlighting the cellular consequences engendered by Scn2a deletion. In summary, the findings provide unprecedented insights into the pathway from Scn2a deletion in oligodendrocytes to sensory abnormalities in ASD, underscoring the integral role of Scn2a -mediated myelination in auditory responses. This research thereby provides novel insights into the intricate tapestry of genetic and cellular interactions inherent in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

5. Chen X, Birey F, Li MY, Revah O, Levy R, Thete MV, Reis N, Kaganovsky K, Onesto M, Sakai N, Hudacova Z, Hao J, Meng X, Nishino S, Huguenard J, Pașca SP. Antisense oligonucleotide therapeutic approach for Timothy syndrome. Nature. 2024; 628(8009): 818-25.

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions(1). TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A(2-6). We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed(7), we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.

Lien vers le texte intégral (Open Access ou abonnement)

6. Conner CM, Ionadi A, Mazefsky CA. Recent Research Points to a Clear Conclusion: Autistic People are Thinking About, and Dying by, Suicide at High Rates. Pa J Posit Approaches. 2023; 12(3): 69-76.

Lien vers le texte intégral (Open Access ou abonnement)

7. Corbett BA, Muscatello RA, Cyperski M, Sadikova E, Edmiston EK, McGonigle TW, Calvosa R, Vandekar S. Gender diversity in autistic and neurotypical youth over adolescence and puberty: A longitudinal study. Autism Res. 2024.

Recent research in autism spectrum disorder (ASD) has suggested a higher prevalence of gender diversity in individuals diagnosed with ASD. Adolescence is a critical period for the consolidation of gender identity, yet the extent to which the experience of gender diversity is stable over adolescence and puberty in autistic youth is poorly understood. The aim of the study was to examine the consistency of gender diversity using the gender diversity screening questionnaire for self- and parent-report of youth (GDSQ-S, GDSQ-P) over a four-year longitudinal study of pubertal development in youth with ASD (N = 140, 36 assigned-female-at birth (AFAB)) and typical development (TD, N = 104, 58 assigned-male-at-birth [AMAB]) and their parents. The extent to which diagnosis (ASD vs. TD), assigned sex (AFAB vs. AMAB) and developmental level (age, puberty) predict GDSQ trajectory over time was explored. There was a significant diagnosis by sex-assigned-at-birth by age interaction for GDSQ-S Gender Diversity, p = 0.002, showing higher scores in autistic AFAB youth over adolescence, and TD AFAB showing initially lower, then increasing levels over adolescence. For GDSQ-P, Gender Incongruence was significantly different between the groups, p = 0.032, showing higher incongruence for autistic AFAB around age 10, decreasing between age 12-14 before increasing again, while TD AFAB evidence the inverse trend. AMAB trends were stable. The significant diagnostic, developmental and sex-based differences indicate AFAB youth experience greater gender diversity that evolves over development. Findings suggest gender identity formation is nuanced and may be influenced by pubertal progression, hormonal patterns, and psychosocial factors. Results underscore the need for enhanced understanding of the unique, dynamic profiles of females-assigned-at-birth.

Lien vers le texte intégral (Open Access ou abonnement)

8. Dudas A, Nakahara TS, Pellissier LP, Chamero P. Parenting behaviors in mice: olfactory mechanisms and features in models of autism spectrum disorders. Neurosci Biobehav Rev. 2024: 105686.

Rodents, along with numerous other mammals, heavily depend on olfactory cues to navigate their social interactions. Processing of olfactory sensory inputs is mediated by conserved brain circuits that ultimately trigger social behaviors, such as social interactions and parental care. Although innate, parenting is influenced by internal states, social experience, genetics, and the environment, and any significant disruption of these factors can impact the social circuits. Here, we review the molecular mechanisms and social circuits from the olfactory epithelium to central processing that initiate parental behaviors and their dysregulations that may contribute to the social impairments in mouse models of autism spectrum disorders (ASD). We discuss recent advances of the crucial role of olfaction in parental care, its consequences for social interactions, and the reciprocal influence on social interaction impairments in mouse models of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

9. Farmer C, Kaat AJ, Edwards MC, Lecavalier L. Measurement Invariance in Intellectual and Developmental Disability Research. Am J Intellect Dev Disabil. 2024; 129(3): 191-8.

Measurement invariance (MI) is a psychometric property of an instrument indicating the degree to which scores from an instrument are comparable across groups. In recent years, there has been a marked uptick in publications using MI in intellectual and developmental disability (IDD) samples. Our goal here is to provide an overview of why MI is important to IDD researchers and to describe some challenges to evaluating it, with an eye towards nudging our subfield into a more thoughtful and measured interpretation of studies using MI.

Lien vers le texte intégral (Open Access ou abonnement)

10. Hempkin N, Sivaraman M, Barnes-Holmes D. Deictic Relational Responding and Perspective-Taking in Autistic Individuals: A Scoping Review. Perspect Behav Sci. 2024; 47(1): 107-37.

Perspective-taking skills are crucial for successful social interactions and some autistic individuals seem to demonstrate great difficulty in this area. The concept continues to generate clinical and research interest across mainstream psychology and within behavior analysis. Within behavior analysis, relational frame theorists have argued that deictic relational responding is critically involved in perspective-taking. We conducted a systematic search of the behavior analytic studies on deictic relational responding and perspective-taking in autistic individuals to highlight methods used to test perspective-taking and deictic relations, methods to train these if deficits were observed, and evidence for a relationship between deictic relational responding and perspective-taking. Seven studies met inclusion criteria and we conducted a descriptive analysis of these studies. We found some variation in the methods used to test and train perspective-taking through deictic relations. Only three of the studies attempted to demonstrate a link between deictic relational responding and perspective-taking. Overall, our review highlighted a need for more research into deictic relational responding and perspective-taking in autistic individuals, and we discussed specific areas for future research.

Lien vers le texte intégral (Open Access ou abonnement)

11. Hongo M, Oshima F, Guan S, Takahashi T, Nitta Y, Seto M, Hull L, Mandy W, Ohtani T, Tamura M, Shimizu E. Reliability and validity of the Japanese version of the camouflaging autistic traits questionnaire. Autism Res. 2024.

This study investigated the factor structure and determined the reliability and validity of the Camouflaging Autistic Traits Questionnaire-Japanese version (CAT-Q-J) among 204 autistic and 410 non-autistic people. Since a confirmatory factor analysis revealed no factor validity of the CAT-Q-J for both autistic and non-autistic adults, an exploratory factor analysis was conducted to ensure the psychometric properties matched those of the original scale as much as possible. The results showed the CAT-Q-J comprised three subscales, a four-item compensation subscale, a five-item masking scale, and a five-item assimilation subscale. The overall CAT-Q-J and all three subscales showed sufficient internal consistency and moderate-to-good and stable test-retest reliability in both the autistic and non-autistic samples. Convergent validity was also supported by the correlations found with measures of autistic traits, well-being, anxiety, and depression. Different from the original CAT-Q, compensation/masking for the autistic sample was not correlated with mental health or autistic traits. The reliability and the validity of the overall CAT-Q-J were confirmed; however, caution should be exercised when interpreting its subscales.

Lien vers le texte intégral (Open Access ou abonnement)

12. Karimi M, Dhopeshwarkar R, Jiménez F, Ryan S, Plourde E. Improving Data Infrastructure for Person-Centered Outcomes Research on Intellectual and Developmental Disabilities. Am J Intellect Dev Disabil. 2024; 129(3): 231-41.

Individuals with intellectual and developmental disabilities (IDD) continue to experience disparities in health and well-being despite improved provisions of person-centered care. Patient-centered outcomes research (PCOR) translates evidence into practice for meaningful outcomes. This piece describes findings from an environmental scan and stakeholder outreach to identify and prioritize opportunities to enhance IDD PCOR data infrastructure. These opportunities include developing a standardized research definition; advancing data standards for service systems; improving capture of IDD at point of care; developing standardized outcome measures; and encouraging Medicaid data use for IDD research. Within this piece, we discuss the implications of addressing data gaps for enhanced research. While the identified activities provide a path towards advancing IDD PCOR data infrastructure, collaborative efforts between government, researchers, and others are paramount.

Lien vers le texte intégral (Open Access ou abonnement)

13. Kim NY, He J, Wu Q, Dai N, Kohlhoff K, Turner J, Paul LK, Kennedy DP, Adolphs R, Navalpakkam V. Smartphone-based gaze estimation for in-home autism research. Autism Res. 2024.

Atypical gaze patterns are a promising biomarker of autism spectrum disorder. To measure gaze accurately, however, it typically requires highly controlled studies in the laboratory using specialized equipment that is often expensive, thereby limiting the scalability of these approaches. Here we test whether a recently developed smartphone-based gaze estimation method could overcome such limitations and take advantage of the ubiquity of smartphones. As a proof-of-principle, we measured gaze while a small sample of well-assessed autistic participants and controls watched videos on a smartphone, both in the laboratory (with lab personnel) and in remote home settings (alone). We demonstrate that gaze data can be efficiently collected, in-home and longitudinally by participants themselves, with sufficiently high accuracy (gaze estimation error below 1° visual angle on average) for quantitative, feature-based analysis. Using this approach, we show that autistic individuals have reduced gaze time on human faces and longer gaze time on non-social features in the background, thereby reproducing established findings in autism using just smartphones and no additional hardware. Our approach provides a foundation for scaling future research with larger and more representative participant groups at vastly reduced cost, also enabling better inclusion of underserved communities.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kuo NC, Wang Y. [Recent advances in the virtual reality technology for treating children with autism spectrum disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2024; 26(4): 414-9.

Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders in children, and there are currently no specific treatments, with the main interventions focusing on educational training and behavioral correction. Virtual reality, as an emerging technology, is a computer-based environmental simulation system that achieves interactive dynamics and immersive experiences by integrating information from multiple sources. In recent years, it has been gradually applied in intervention training for children with ASD. This paper reviews the recent studies on the effects of virtual reality intervention on emotional cognition, social skills, daily living skills, motor skills, and specific phobias in children with ASD, offering a new direction for ASD intervention training.

Lien vers le texte intégral (Open Access ou abonnement)

15. Mantzalas J, Richdale AL, Li X, Dissanayake C. Measuring and validating autistic burnout. Autism Res. 2024.

Researchers have begun to explore the characteristics and risk factors for autistic burnout, but assessment tools are lacking. Our study comprehensively examined and compared the psychometric properties of the unpublished 27-item AASPIRE Autistic Burnout Measure (ABM), and personal and work scales of the Copenhagen Burnout Inventory (CBI) to evaluate their efficacy as screening measures for autistic burnout, with a group of 238 autistic adults. Exploratory factor analyses (EFA) revealed a 4-factor structure for the ABM and a 2-factor structure for the CBI personal scale (CBI-P). Factorial validity and dimensionality were examined with four exploratory models which indicated a unidimensional structure for the ABM with an overarching ‘Autistic Burnout’ construct, and multidimensional CBI-P structure comprising two subscales and overarching ‘Personal Burnout’ construct. Other reliability and validity indicators included Spearman correlations, analysis of variance, receiver operating characteristics, sensitivity, specificity, and intra-class correlations (ICC). The ABM and CBI-P were strongly correlated with depression, anxiety, stress, and fatigue. Unexpectedly, correlations between the burnout measures and camouflaging, and wellbeing measures were moderate. Potential overlap between burnout and depression and fatigue was examined through EFA, which supported convergent validity of the ABM and depression measure, while correlations and ICC analyses revealed mixed results. We concluded that the ABM and the CBI-P Emotional Exhaustion subscale were valid preliminary screening tools for autistic burnout. Testing with larger and more diverse autistic samples is required to further examine the psychometric properties of the ABM, and to understand the relationships between autistic burnout and depression, and masking.

Lien vers le texte intégral (Open Access ou abonnement)

16. Mittertreiner EJ, Ng-Cordell E, McVey AJ, Kerns CM. Research methods at the intersection of gender diversity and autism: A scoping review. Autism. 2024: 13623613241245595.

Research has increasingly focused on the intersection between gender diversity and autism. To better understand this literature, this scoping review systematically searched five databases for peer-reviewed literature on gender diversity and autism published between 2018 and 2023. Included studies (N = 84) were of English language, featured original qualitative or quantitative findings, and examined a psychosocial connection between autism and gender spectra variables. Most studies focused on measuring prevalence of autism among gender-diverse individuals. While the overall study rigor was acceptable, weaknesses in measurement, sample selection, and definition of key terms were noted. Promisingly, studies in this area appear to be shifting away from a pathologizing lens and towards research methods that engage in meaningful collaboration with the autistic, gender-diverse community to investigate how to best enhance the quality of life and wellbeing of this population.

Lien vers le texte intégral (Open Access ou abonnement)

17. Myers RK, Labows C, McDonald CC, Yerys BE, Sartin EB, Carey ME, Mollen CJ, Curry AE. Preparing to « Live a Life of Possibilities »: Experiences of Healthcare Providers Readying Autistic Adolescents and Their Families for Independent Driving. J Autism Dev Disord. 2024.

Autistic adolescents and their families may experience barriers to transportation, including independent driving, which is critical to supporting quality of life and engagement in social, educational, and employment opportunities. Healthcare providers may feel unprepared to provide guidance to autistic adolescents, although they are among the professionals families turn to for guidance. This study describes providers’ experiences supporting autistic adolescents and families in the decision to pursue licensure and identifies barriers experienced in providing support. We conducted interviews with 15 healthcare providers focused on how they support autistic adolescents and their families in navigating topics related to independence, driving, and transportation. Key themes identified included: importance of understanding adolescents’ perspectives and motivations, approaches to readying caregivers for children to pursue driving, and role of providers in fostering agreement between adolescents and caregivers. Results reflect healthcare providers as intermediaries between autistic adolescents and caregivers making the decision to pursue licensure and bring families to consensus. Our findings emphasize the importance of healthcare providers, in collaboration with community-based providers, in supporting autistic adolescents and their families considering licensure. Improving conversations between providers and families provides opportunity to better support quality of life among autistic adolescents and their caregivers navigating the transition to independence.

Lien vers le texte intégral (Open Access ou abonnement)

18. O’Neill S, O’Donnell GM. Identifying autistic children: Priorities for research arising from a systematic review of parents’ experiences of the assessment process. Autism. 2024: 13623613241243107.

Hearing about parents’ experiences of having their child recognised as autistic could help improve the supports offered to parents. Our article may also help guide future research on this topic. We made a list of the type of research that interested us. We searched the studies already completed, only studying the research that matched our interests. After reading the studies, we rated their quality using the Critical Appraisal Skills Programme tool.It became clear that parents went through four phases during the identification process. The first phase occurred before their child was identified as autistic. The second involved the actual assessment of their child. Parents’ emotional reactions to the news were the focus of the third phase. The final phase occurred after their child was identified as autistic. We discuss the findings of our research. As there are sensitivities involved in conducting research on this topic, we identify how researchers can ensure that their research is of the best quality. We are committed to respecting the human rights of all involved, so we emphasise the need for professionals to develop good relationships with the parents of autistic children. Researchers have recently come to see autism as typical of human diversity. We encourage the professionals involved to adopt this understanding of autistic children and make practical suggestions to enable them to do so.

Lien vers le texte intégral (Open Access ou abonnement)

19. Ouyang Y, Feng J, Wang T, Xue Y, Mohamed ZA, Jia F. Comparison of the efficacy of parent-mediated NDBIs on developmental skills in children with ASD and fidelity in parents: a systematic review and network meta-analysis. BMC Pediatr. 2024; 24(1): 270.

BACKGROUND: Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children’s developmental skills and parent fidelity. METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. RESULTS: Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children’s social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children’s language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. CONCLUSION: In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.

Lien vers le texte intégral (Open Access ou abonnement)

20. Peristeri E, Frantzidis CA, Andreou M. Reading comprehension differences between children with Autism Spectrum Disorder and low cognitive abilities and children with Autism Spectrum Disorder and intact cognitive skills: the roles of decoding, fluency and morphosyntax. Front Psychol. 2024; 15: 1357590.

INTRODUCTION: Reading comprehension is one of the most important skills learned in school and it has an important contribution to the academic success of children with Autism Spectrum Disorder (ASD). Though previous studies have investigated reading comprehension difficulties in ASD and highlighted factors that contribute to these difficulties, this evidence has mainly stemmed from children with ASD and intact cognitive skills. Also, much emphasis has been placed on the relation between reading comprehension and word recognition skills, while the role of other skills, including fluency and morphosyntax, remains underexplored. This study addresses these gaps by investigating reading comprehension in two groups of school-aged children with ASD, one with intact and one with low cognitive abilities, also exploring the roles of word decoding, fluency and morphosyntax in each group’s reading comprehension performance. METHODS: The study recruited 16 children with ASD and low cognitive abilities, and 22 age-matched children with ASD and intact cognitive skills. The children were assessed on four reading subdomains, namely, decoding, fluency, morphosyntax, and reading comprehension. RESULTS: The children with ASD and low cognitive abilities scored significantly lower than their peers with intact cognitive abilities in all reading subdomains, except for decoding, verb production and compound word formation. Regression analyses showed that reading comprehension in the group with ASD and intact cognitive abilities was independently driven by their decoding and fluency skills, and to a lesser extent, by morphosyntax. On the other hand, the children with ASD and low cognitive abilities mainly drew on their decoding, and to a lesser extent, their morphosyntactic skills to perform in reading comprehension. DISCUSSION: The results suggest that reading comprehension was more strongly affected in the children with ASD and low cognitive abilities as compared to those with intact cognitive skills. About half of the children with ASD and intact cognitive skills also exhibited mild-to-moderate reading comprehension difficulties, further implying that ASD may influence reading comprehension regardless of cognitive functioning. Finally, strengths in decoding seemed to predominantly drive cognitively-impaired children’s reading performance, while the group with ASD and intact cognitive skills mainly recruited fluency and metalinguistic lexical skills to cope with reading comprehension demands, further suggesting that metalinguistic awareness may be a viable way to enhance reading comprehension in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

21. Phan J, Calvo DC, Nair D, Jain S, Montagne T, Dietsche S, Blanchard K, Treadwell S, Adams J, Krajmalnik-Brown R. Precision synbiotics increase gut microbiome diversity and improve gastrointestinal symptoms in a pilot open-label study for autism spectrum disorder. mSystems. 2024: e0050324.

The efficacy of prebiotics and probiotics (synbiotics when combined) to improve symptoms associated with autism spectrum disorder (ASD) has shown considerable inter-study variation, likely due to the complex, heterogeneous nature of the disorder and its associated behavioral, developmental, and gastrointestinal symptoms. Here, we present a precision synbiotic supplementation study in 296 children and adults diagnosed with ASD versus 123 age-matched neurotypical controls. One hundred seventy ASD participants completed the study. Baseline and post-synbiotic assessment of ASD and gastrointestinal (GI) symptoms and deep metagenomic sequencing were performed. Within the ASD cohort, there were significant differences in microbes between subpopulations based on the social responsiveness scale (SRS2) survey (Prevotella spp., Bacteroides, Fusicatenibacter, and others) and gluten and dairy-free diets (Bifidobacterium spp., Lactococcus, Streptococcus spp., and others). At the baseline, the ASD cohort maintained a lower taxonomic alpha diversity and significant differences in taxonomic composition, metabolic pathways, and gene families, with a greater proportion of potential pathogens, including Shigella, Klebsiella, and Clostridium, and lower proportions of beneficial microbes, including Faecalibacterium compared to controls. Following the 3-month synbiotic supplementation, the ASD cohort showed increased taxonomic alpha diversity, shifts in taxonomy and metabolic pathway potential, and improvements in some ASD-related symptoms, including a significant reduction in GI discomfort and overall improved language, comprehension, cognition, thinking, and speech. However, the open-label study design may include some placebo effects. In summary, we found that precision synbiotics modulated the gut microbiome and could be used as supplementation to improve gastrointestinal and ASD-related symptoms. IMPORTANCE: Autism spectrum disorder (ASD) is prevalent in 1 out of 36 children in the United States and contributes to health, financial, and psychological burdens. Attempts to identify a gut microbiome signature of ASD have produced varied results. The limited pre-clinical and clinical population sizes have hampered the success of these trials. To understand the microbiome associated with ASD, we employed whole metagenomic shotgun sequencing to classify microbial composition and genetic functional potential. Despite being one of the most extensive ASD post-synbiotic assessment studies, the results highlight the complexity of performing such a case-control supplementation study in this population and the potential for a future therapeutic approach in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

22. Punatar R, Angkustsiri K, Kair LR, Tancredi DJ, Harvey DJ, Schmidt RJ. Association of Breastfeeding Duration with Neurodevelopmental Outcomes in an Enriched Familial Likelihood Cohort for Autism Spectrum Disorder. Child Psychiatry Hum Dev. 2024.

This study aimed to compare the breastfeeding (BF) duration of the younger siblings of children with ASD in an enriched-likelihood cohort for autism spectrum disorder (ASD), and to determine whether longer BF duration was associated with differences in neurodevelopmental outcomes in this cohort. Information on BF practices was collected via surveys in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. Developmental evaluations, including the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, were conducted by expert clinicians. Participants’ neurodevelopmental outcome was classified by an algorithm into three groups: typical development, ASD, and non-typical development. The median duration of BF was 10.70 months (interquartile range of 12.07 months). There were no significant differences in the distribution of duration of BF among the three neurodevelopmental outcome categories. Children in this enriched-likelihood cohort who were breastfed for > 12 months had significantly higher scores on cognitive testing compared to those who were breastfed for 0-3 months. There was no significant difference in ASD symptomatology or ASD risk based on BF duration.

Lien vers le texte intégral (Open Access ou abonnement)

23. Regener P, Heffer N, Love SA, Petrini K, Pollick F. Differences in audiovisual temporal processing in autistic adults are specific to simultaneity judgments. Autism Res. 2024.

Research has shown that children on the autism spectrum and adults with high levels of autistic traits are less sensitive to audiovisual asynchrony compared to their neurotypical peers. However, this evidence has been limited to simultaneity judgments (SJ) which require participants to consider the timing of two cues together. Given evidence of partly divergent perceptual and neural mechanisms involved in making temporal order judgments (TOJ) and SJ, and given that SJ require a more global type of processing which may be impaired in autistic individuals, here we ask whether the observed differences in audiovisual temporal processing are task and stimulus specific. We examined the ability to detect audiovisual asynchrony in a group of 26 autistic adult males and a group of age and IQ-matched neurotypical males. Participants were presented with beep-flash, point-light drumming, and face-voice displays with varying degrees of asynchrony and asked to make SJ and TOJ. The results indicated that autistic participants were less able to detect audiovisual asynchrony compared to the control group, but this effect was specific to SJ and more complex social stimuli (e.g., face-voice) with stronger semantic correspondence between the cues, requiring a more global type of processing. This indicates that audiovisual temporal processing is not generally different in autistic individuals and that a similar level of performance could be achieved by using a more local type of processing, thus informing multisensory integration theory as well as multisensory training aimed to aid perceptual abilities in this population.

Lien vers le texte intégral (Open Access ou abonnement)

24. Shpigelman CN, Araten-Bergman T. Adults With IDD in Supported Accommodation During COVID-19 Lockdown: The Families’ Perspective. Am J Intellect Dev Disabil. 2024; 129(3): 215-30.

The present study aims to understand and describe family caregivers’ perceptions and experiences regarding contact and relationships with their adult relatives with intellectual and developmental disabilities (IDD) living in supported accommodation during the COVID-19 lockdown. A qualitative phenomenological approach was applied in which 19 Israeli family caregivers (parents and siblings) were interviewed. Inductive thematic analysis revealed themes at the microsystem level (the resident, the caregiver, and their relationship), and at the mesosystem level (the caregivers’ interactions with service providers and other residents’ families). The findings highlight the pivotal role of family caregivers in times of uncertainty and the need to develop explicit policies and mechanisms to facilitate family engagement in the residents’ lives.

Lien vers le texte intégral (Open Access ou abonnement)

25. Strang JF, Fischbach AL, Rao S, Clawson A, Knauss M, Bernstein SN, van der Miesen AIR, Inge AP, Alonzo K, Zeroth J, Kenworthy L, Morgan CI, Brandt A, Moore CC, Ahlers K, Jankowski MK, McClellan LS, Henise SB, Cap CJ, Exley SL, Youmatz A, Song M, McLaren JL, Parchem B. Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults. Clin Neuropsychol. 2024: 1-37.

Objective: Situated in Children’s National Hospital (CNH)’s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP’s feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Lien vers le texte intégral (Open Access ou abonnement)

26. Tokatly Latzer I, Roullet JB, Afshar-Saber W, Lee HHC, Bertoldi M, McGinty GE, DiBacco ML, Arning E, Tsuboyama M, Rotenberg A, Opladen T, Jeltsch K, García-Cazorla À, Juliá-Palacios N, Gibson KM, Sahin M, Pearl PL. Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder. J Neurodev Disord. 2024; 16(1): 21.

BACKGROUND: Succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a model neurometabolic disease at the fulcrum of translational research within the Boston Children’s Hospital Intellectual and Developmental Disabilities Research Centers (IDDRC), including the NIH-sponsored natural history study of clinical, neurophysiological, neuroimaging, and molecular markers, patient-derived induced pluripotent stem cells (iPSC) characterization, and development of a murine model for tightly regulated, cell-specific gene therapy. METHODS: SSADHD subjects underwent clinical evaluations, neuropsychological assessments, biochemical quantification of γ-aminobutyrate (GABA) and related metabolites, electroencephalography (standard and high density), magnetoencephalography, transcranial magnetic stimulation, magnetic resonance imaging and spectroscopy, and genetic tests. This was parallel to laboratory molecular investigations of in vitro GABAergic neurons derived from induced human pluripotent stem cells (hiPSCs) of SSADHD subjects and biochemical analyses performed on a versatile murine model that uses an inducible and reversible rescue strategy allowing on-demand and cell-specific gene therapy. RESULTS: The 62 SSADHD subjects [53% females, median (IQR) age of 9.6 (5.4-14.5) years] included in the study had a reported symptom onset at ∼ 6 months and were diagnosed at a median age of 4 years. Language developmental delays were more prominent than motor. Autism, epilepsy, movement disorders, sleep disturbances, and various psychiatric behaviors constituted the core of the disorder’s clinical phenotype. Lower clinical severity scores, indicating worst severity, coincided with older age (R= -0.302, p = 0.03), as well as age-adjusted lower values of plasma γ-aminobutyrate (GABA) (R = 0.337, p = 0.02) and γ-hydroxybutyrate (GHB) (R = 0.360, p = 0.05). While epilepsy and psychiatric behaviors increase in severity with age, communication abilities and motor function tend to improve. iPSCs, which were differentiated into GABAergic neurons, represent the first in vitro neuronal model of SSADHD and express the neuronal marker microtubule-associated protein 2 (MAP2), as well as GABA. GABA-metabolism in induced GABAergic neurons could be reversed using CRISPR correction of the pathogenic variants or mRNA transfection and SSADHD iPSCs were associated with excessive glutamatergic activity and related synaptic excitation. CONCLUSIONS: Findings from the SSADHD Natural History Study converge with iPSC and animal model work focused on a common disorder within our IDDRC, deepening our knowledge of the pathophysiology and longitudinal clinical course of a complex neurodevelopmental disorder. This further enables the identification of biomarkers and changes throughout development that will be essential for upcoming targeted trials of enzyme replacement and gene therapy.

Lien vers le texte intégral (Open Access ou abonnement)

27. Voelker R. What Is Autism Spectrum Disorder?. Jama. 2024.

This JAMA Patient Page describes autism spectrum disorder (ASD) and its signs and symptoms, diagnosis, and therapy options. eng.

Lien vers le texte intégral (Open Access ou abonnement)

28. Wang C, Xiao Z, Xu Y, Zhang Q, Chen J. A novel approach for ASD recognition based on graph attention networks. Front Comput Neurosci. 2024; 18: 1388083.

Early detection and diagnosis of Autism Spectrum Disorder (ASD) can significantly improve the quality of life for affected individuals. Identifying ASD based on brain functional connectivity (FC) poses a challenge due to the high heterogeneity of subjects’ fMRI data in different sites. Meanwhile, deep learning algorithms show efficacy in ASD identification but lack interpretability. In this paper, a novel approach for ASD recognition is proposed based on graph attention networks. Specifically, we treat the region of interest (ROI) of the subjects as node, conduct wavelet decomposition of the BOLD signal in each ROI, extract wavelet features, and utilize them along with the mean and variance of the BOLD signal as node features, and the optimized FC matrix as the adjacency matrix, respectively. We then employ the self-attention mechanism to capture long-range dependencies among features. To enhance interpretability, the node-selection pooling layers are designed to determine the importance of ROI for prediction. The proposed framework are applied to fMRI data of children (younger than 12 years old) from the Autism Brain Imaging Data Exchange datasets. Promising results demonstrate superior performance compared to recent similar studies. The obtained ROI detection results exhibit high correspondence with previous studies and offer good interpretability.

Lien vers le texte intégral (Open Access ou abonnement)

29. Whelan TP, Daly E, Puts NA, Smith P, Allison C, Baron-Cohen S, Malievskaia E, Murphy DGM, McAlonan GM. The ‘PSILAUT’ protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin. BMC Psychiatry. 2024; 24(1): 319.

BACKGROUND: The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT(2A) receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin – principally, but not exclusively, 5HT(2A) receptor pathways-function differently in autistic and non-autistic adults. METHODS: The ‘PSILAUT’ « shiftability » study is a case-control study autistic and non-autistic adults. How neural responses ‘shift’ in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order. RESULTS: This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function. CONCLUSIONS: This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches. TRIAL REGISTRATION: NCT05651126.

Lien vers le texte intégral (Open Access ou abonnement)

30. Wu Y, Yang T, Chen HY, Long D, Xiang XL, Feng YR, Wei QH, Chen J, Li TY. [Serum folate and vitamin B(12) levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2024; 26(4): 371-7.

OBJECTIVES: To investigate the levels of serum folate and vitamin B(12) (VB(12)) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB(12) were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB(12) in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB(12) levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB(12) levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB(12) levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB(12) levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB(12) levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Lien vers le texte intégral (Open Access ou abonnement)

31. Yang Y, Chen D, Cai K, Zhu L, Shi Y, Dong X, Sun Z, Qiao Z, Yang Y, Zhang W, Mao H, Chen A. Effects of mini-basketball training program on social communication impairments and regional homogeneity of brain functions in preschool children with autism spectrum disorder. BMC Sports Sci Med Rehabil. 2024; 16(1): 92.

BACKGROUND: Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise has been shown to improve SCI, this finding has not been supported by comprehensive scientific evidence. Existing research has established a strong link between the SCI in children with ASD and abnormalities in regional homogeneity (ReHo). Therefore, investigating the effects of physical exercise on SCI and Reho in patients with ASD may help to elucidate the neurological mechanisms involved. METHODS: The present study included 30 preschool children diagnosed with ASD, with 15 participants in each group (experimental and control). The experimental group underwent a 12-week mini-basketball training program (MBTP) based on routine behavioral rehabilitation, while the control group only received routine behavioral rehabilitation. The Social Responsiveness Scale-Second Edition (SRS-2) was employed to assess SCI in both groups. Resting-state functional magnetic resonance imaging technology was used to evaluate ReHo in both groups. RESULTS: After 12-week of MBTP, significant group × time interactions were observed between the experimental and control groups in total SRS-2 scores (F = 14.514, p < 0.001, η(p)(2) = 0.341), as well as in the domains of social cognition (F = 15.620, p < 0.001, η(p)(2) = 0.358), social communication (F = 12.460, p < 0.01, η(p)(2) = 0.308), and autistic mannerisms (F = 9.970, p < 0.01, η(p)(2) = 0.263). No statistical difference was found in the scores for the social awareness subscale and social motivation subscale in the group × time interaction (all p > 0.05). The experimental group exhibited increased ReHo in the right Cerebellum_Crus1 and right parahippocampal gyrus, coupled with decreased ReHo in the left middle frontal gyrus (orbital part), left superior frontal gyrus (dorsolateral), left postcentral gyrus, and right superior parietal gyrus. Furthermore, a decrease in ReHo in the left postcentral gyrus positively correlated with changes in social communication scores in SCI behaviors (p < 0.05). CONCLUSIONS: Our study underscores the effectiveness of a 12-week MBTP in ameliorating SCI and abnormalities in ReHo among preschool children with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973; August 5, 2019).

Lien vers le texte intégral (Open Access ou abonnement)

32. Zhan X, Asmara H, Pfaffinger P, Turner RW. Calcium-dependent regulation of neuronal excitability is rescued in Fragile X Syndrome by a tat-conjugated N-terminal fragment of FMRP. J Neurosci. 2024.

Fragile X Syndrome arises from the loss of Fragile X Messenger Ribonucleoprotein (FMRP) needed for normal neuronal excitability and circuit functions. Recent work revealed that FMRP contributes to mossy fiber LTP by adjusting Kv4 A-type current availability through interactions with a Cav3-Kv4 ion channel complex, yet the mechanism has not yet been defined. In this study using wild-type and Fmr1 knockout (KO) tsA-201 cells and cerebellar sections from male Fmr1 KO mice, we show that FMRP associates with all subunits of the Cav3.1-Kv4.3-KChIP3 complex, and is critical to enabling calcium-dependent shifts in Kv4.3 inactivation to modulate A-type current. Specifically, upon depolarization Cav3 calcium influx activates dual specific phosphatase 1/6 (DUSP1/6) to deactivate ERK1/2 (ERK) and lower phosphorylation of Kv4.3, a signalling pathway that does not function in Fmr1 KO cells. In Fmr1 KO mouse tissue slices cerebellar granule cells exhibit a hyperexcitable response to membrane depolarizations. Either incubating Fmr1 KO cells or in vivo administration of a tat-conjugated FMRP N-terminus fragment (FMRP-N-tat) rescued Cav3-Kv4 function and granule cell excitability, with a decrease in the level of DUSP6. Together these data reveal a Cav3-activated DUSP signalling pathway critical to the function of a FMRP-Cav3-Kv4 complex that is misregulated in Fmr1 KO conditions. Moreover, FMRP-N-tat restores function of this complex to rescue calcium-dependent control of neuronal excitability as a potential therapeutic approach to alleviating the symptoms of Fragile X Syndrome.Significance Statement Changes in neuronal excitability and ion channel functions have been a focus in studies of Fragile X Syndrome. Previous work identified ion channels that are regulated by FMRP through either protein translation or direct protein-protein interactions. The current study reveals FMRP as a constitutive member of a Cav3-Kv4 complex that is required for a Cav3-DUSP-ERK signalling pathway to increase A-type current and reduce cerebellar granule cell excitability. In Fmr1 KO cells, Cav3-Kv4 function and calcium-dependent modulation of A-type current is lost, leading to a hyperexcitable state of cerebellar granule cells. Pretreating with FMRP-N-tat restores all Cav3-Kv4 function and granule cell excitability, providing support for FMRP-tat peptide treatment as a potential therapeutic strategy for Fragile X Syndrome.

Lien vers le texte intégral (Open Access ou abonnement)