1. Baixauli I, Rosello B, Berenguer C, Téllez de Meneses M, Miranda A. Reading and Writing Skills in Adolescents With Autism Spectrum Disorder Without Intellectual Disability. Frontiers in psychology. 2021; 12: 646849.

The purpose of this study is to extend the knowledge about academic achievement in individuals with autism spectrum disorder (ASD). To this end, first, we analyzed differences in a wide range of reading and writing skills in adolescents with ASD without intellectual disability (ASD-WID) and adolescents with typical development (TD). Second, these two groups were compared on academic outcomes in core subjects and indicators of successful transition to secondary school. Third, the potential contribution of literacy skills to academic outcomes was examined in the two groups. Participants were 56 adolescents between 12 and 14 years old, 30 with ASD-WID and 26 with TD. Results showed no significant differences between the two groups on measures of reading fluency or literal and inferential comprehension. However, the performance of the group with ASD was significantly lower on reading comprehension processes that assess cognitive flexibility. Regarding their written expression skills, significant differences were observed between the group with ASD and the group with TD on most of the indicators analyzed as: productivity, lexical diversity, and overall coherence (resolution component). In addition, findings showed that the deficits in reading and writing observed in the adolescents with ASD significantly affected their academic achievement, which was lower than that of their peers with TD and below what would be expected based on their intellectual capacity. Moreover, their families’ perceptions of the transition to high school reflected worse adjustment and lower self-esteem, confidence, and motivation.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bashirian S, Seyedi M, Razjouyan K, Jenabi E. The Association between Labor Induction and Autism Spectrum Disorders Among Children: A Meta-Analysis. Current pediatric reviews. 2021; 17(3): 238-43.

BACKGROUND: It was hypothesized that the oxytocin used during labor could increase the risk of neurodevelopmental disorders, such as ASD. OBJECTIVE: This meta-analysis pooled all observational studies to obtain the association between labor induction and the risk of ASD among children. We identified all published studies up to August 2020 by search in PubMed, Scopus, Web of Science and gray literature. The pooled odds ratios (OR), relative ratio (RR) and 95% confidence intervals (CI (were calculated as random effect estimates of association among studies. RESULTS: The pooled estimates of OR and RR reported a significant association between labor induction and ASD among children, respectively (OR = 1.09, 95% CI = 1.04 to 1.15) and (RR = 1.06, 95% CI = 1.02 to 1.09). The subgroup analyses were performed based on the adjusted form and design of studies. OR in crude and adjusted studies were reported to be 1.25(1.01, 1.49) and 1.08(1.02, 1.14), respectively. A significant association was found in adjusted and crude studies. There is no significant association between labor induction and ASD in case-control studies (OR=1.08, 95% CI = 0.99, 1.17). CONCLUSION: The findings showed that labor induction is associated with an increased risk of ASD among children. Therefore, the findings support that clinical use of oxytocin during labor has a significant negative impact on the long-term mental health of children.

Lien vers le texte intégral (Open Access ou abonnement)

3. Budisteanu M, Papuc SM, Streata I, Cucu M, Pirvu A, Serban-Sosoi S, Erbescu A, Andrei E, Iliescu C, Ioana D, Severin E, Ioana M, Arghir A. The Phenotypic Spectrum of 15q13.3 Region Duplications: Report of 5 Patients. Genes. 2021; 12(7).

Chromosome 15q13.3 microduplications are associated with a wide spectrum of clinical presentations ranging from normal to different neuropsychiatric conditions, such as developmental delay (DD), intellectual disability (ID), epilepsy, hypotonia, autism spectrum disorders (ASD), attention-deficit hyperactivity disorder, and schizophrenia. The smallest region of overlap for 15q13.3 duplications encompasses the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, a strong candidate for the behavioral abnormalities. We report on a series of five patients with 15q13.3 duplications detected by chromosomal microarray. The size of the duplications ranged from 378 to 537 kb, and involved the CHRNA7 gene in all patients. The most common clinical features, present in all patients, were speech delay, autistic behavior, and muscle hypotonia; DD/ID was present in three patients. One patient presented epileptic seizures; EEG anomalies were observed in three patients. No consistent dysmorphic features were noted. Neuroimaging studies revealed anomalies in two patients: Dandy-Walker malformation and a right temporal cyst. 15q13.3 duplications are associated with various neuropsychiatric features, including speech delay, hypotonia, ASD, and ID, also present in our patient group. Our study brings detailed clinical and molecular data from five ASD patients with 15q13.3 microduplications involving the CHRNA7 gene, contributing to the existing knowledge about the association of 15q13.3 duplications with neuropsychiatric phenotypes.

Lien vers le texte intégral (Open Access ou abonnement)

4. Chatterjee R, Paluh JL, Chowdhury S, Mondal S, Raha A, Mukherjee A. SyNC, a Computationally Extensive and Realistic Neural Net to Identify Relative Impacts of Synaptopathy Mechanisms on Glutamatergic Neurons and Their Networks in Autism and Complex Neurological Disorders. Frontiers in cellular neuroscience. 2021; 15: 674030.

Synaptic function and experience-dependent plasticity across multiple synapses are dependent on the types of neurons interacting as well as the intricate mechanisms that operate at the molecular level of the synapse. To understand the complexity of information processing at synaptic networks will rely in part on effective computational models. Such models should also evaluate disruptions to synaptic function by multiple mechanisms. By co-development of algorithms alongside hardware, real time analysis metrics can be co-prioritized along with biological complexity. The hippocampus is implicated in autism spectrum disorders (ASD) and within this region glutamatergic neurons constitute 90% of the neurons integral to the functioning of neuronal networks. Here we generate a computational model referred to as ASD interrogator (ASDint) and corresponding hardware to enable in silicon analysis of multiple ASD mechanisms affecting glutamatergic neuron synapses. The hardware architecture Synaptic Neuronal Circuit, SyNC, is a novel GPU accelerator or neural net, that extends discovery by acting as a biologically relevant realistic neuron synapse in real time. Co-developed ASDint and SyNC expand spiking neural network models of plasticity to comparative analysis of retrograde messengers. The SyNC model is realized in an ASIC architecture, which enables the ability to compute increasingly complex scenarios without sacrificing area efficiency of the model. Here we apply the ASDint model to analyse neuronal circuitry dysfunctions associated with autism spectral disorder (ASD) synaptopathies and their effects on the synaptic learning parameter and demonstrate SyNC on an ideal ASDint scenario. Our work highlights the value of secondary pathways in regard to evaluating complex ASD synaptopathy mechanisms. By comparing the degree of variation in the synaptic learning parameter to the response obtained from simulations of the ideal scenario we determine the potency and time of the effect of a particular evaluated mechanism. Hence simulations of such scenarios in even a small neuronal network now allows us to identify relative impacts of changed parameters and their effect on synaptic function. Based on this, we can estimate the minimum fraction of a neuron exhibiting a particular dysfunction scenario required to lead to complete failure of a neural network to coordinate pre-synaptic and post-synaptic outputs.

Lien vers le texte intégral (Open Access ou abonnement)

5. Crosswell AD, Sagui-Henson S, Prather AA, Coccia M, Irwin MR, Epel ES. Psychological Resources and Biomarkers of Health in the Context of Chronic Parenting Stress. International journal of behavioral medicine. 2022; 29(2): 175-87.

BACKGROUND: Epidemiological studies link psychological resources to better physical health. One reason may be that psychological resources are protective in stressful contexts. This study tested whether indeed psychological resources are protective against biological degradation for healthy mid-life women under the chronic stress of caring for a child with an autism spectrum disorder diagnosis (« caregivers »). METHODS: We tested whether five types of psychosocial resources (i.e., eudaimonic well-being, autonomy, purpose in life, self-acceptance, and mastery) were associated with biological indices of aging in a sample of mid-life women stratified by chronic stress; half were caregivers (n = 92) and half were mothers of neurotypical children (n = 91; controls). Selected stress and age related biological outcomes were insulin resistance (HOMA-IR), systemic inflammation (IL-6, CRP), and cellular aging (leukocyte telomere length). We tested whether each resource was associated with these biomarkers, and whether caregiving status and high parenting stress moderated that relationship. RESULTS: All the psychological resources except mastery were significantly negatively associated with insulin resistance, while none were related to systemic inflammation or telomere length. The relationships between eudaimonic well-being and HOMA-IR, and self-acceptance and HOMA-IR, were moderated by parental stress; lower resources were associated with higher insulin resistance, but only for women reporting high parental stress. The well-known predictors of age and BMI accounted for 46% of variance in insulin resistance, and psychological resources accounted for an additional 13% of variance. CONCLUSION: These findings suggest that higher eudaimonic well-being and greater self-acceptance may be protective for the metabolic health of mid-life women, and particularly in the context of high parenting stress. This has important implications given the rising rates of both parental stress and metabolic disease, and because psychological interventions can increase eudaimonic well-being and self-acceptance.

Lien vers le texte intégral (Open Access ou abonnement)

6. Dhaliwal J, Qiao Y, Calli K, Martell S, Race S, Chijiwa C, Glodjo A, Jones S, Rajcan-Separovic E, Scherer SW, Lewis S. Contribution of Multiple Inherited Variants to Autism Spectrum Disorder (ASD) in a Family with 3 Affected Siblings. Genes. 2021; 12(7).

Autism Spectrum Disorder (ASD) is the most common neurodevelopmental disorder in children and shows high heritability. However, how inherited variants contribute to ASD in multiplex families remains unclear. Using whole-genome sequencing (WGS) in a family with three affected children, we identified multiple inherited DNA variants in ASD-associated genes and pathways (RELN, SHANK2, DLG1, SCN10A, KMT2C and ASH1L). All are shared among the three children, except ASH1L, which is only present in the most severely affected child. The compound heterozygous variants in RELN, and the maternally inherited variant in SHANK2, are considered to be major risk factors for ASD in this family. Both genes are involved in neuron activities, including synaptic functions and the GABAergic neurotransmission system, which are highly associated with ASD pathogenesis. DLG1 is also involved in synapse functions, and KMT2C and ASH1L are involved in chromatin organization. Our data suggest that multiple inherited rare variants, each with a subthreshold and/or variable effect, may converge to certain pathways and contribute quantitatively and additively, or alternatively act via a 2nd-hit or multiple-hits to render pathogenicity of ASD in this family. Additionally, this multiple-hits model further supports the quantitative trait hypothesis of a complex genetic, multifactorial etiology for the development of ASDs.

Lien vers le texte intégral (Open Access ou abonnement)

7. Egidy Assenza G, Spinardi L, Mariucci E, Balducci A, Ragni L, Ciuca C, Formigari R, Angeli E, Vornetti G, Gargiulo GD, Donti A. Transcatheter Closure of PFO and ASD: Multimodality Imaging for Patient Selection and Perioperative Guidance. Journal of cardiovascular development and disease. 2021; 8(7).

Transcatheter closure of patent foramen ovale (PFO) and secundum type atrial septal defect (ASD) are common transcatheter procedures. Although they share many technical details, these procedures are targeting two different clinical indications. PFO closure is usually considered to prevent recurrent embolic stroke/systemic arterial embolization, ASD closure is indicated in patients with large left-to-right shunt, right ventricular volume overload, and normal pulmonary vascular resistance. Multimodality imaging plays a key role for patient selection, periprocedural monitoring, and follow-up surveillance. In addition to routine cardiovascular examinations, advanced neuroimaging studies, transcranial-Doppler, and interventional transesophageal echocardiography/intracardiac echocardiography are now increasingly used to deliver safely and effectively such procedures. Long-standing collaboration between interventional cardiologist, neuroradiologist, and cardiac imager is essential and it requires a standardized approach to image acquisition and interpretation. Periprocedural monitoring should be performed by experienced operators with deep understanding of technical details of transcatheter intervention. This review summarizes the specific role of different imaging modalities for PFO and ASD transcatheter closure, describing important pre-procedural and intra-procedural details and providing examples of procedural pitfall and complications.

Lien vers le texte intégral (Open Access ou abonnement)

8. Gesi C, Migliarese G, Torriero S, Capellazzi M, Omboni AC, Cerveri G, Mencacci C. Gender Differences in Misdiagnosis and Delayed Diagnosis among Adults with Autism Spectrum Disorder with No Language or Intellectual Disability. Brain sciences. 2021; 11(7).

Autism Spectrum Disorder (ASD) is often unrecognized, especially in mild forms and in women. Studies evaluating features associated with missed/misdiagnosis in men and women with ASD are warranted. 61 subjects (22 females, 39 males, age 28.5 ± 10.8 years) with ASD with no language/intellectual deficit were enrolled in the service for the treatment of psychiatric comorbidities in adults with ASD of the ASST Fatebenefratelli-Sacco in Milan (Italy). A detailed clinical history was gathered, and two self-report questionnaires (Autism Spectrum Quotient-AQ and Adult Autism Subthreshold Spectrum-AdAS Spectrum) were administered. 75.4% received their ASD diagnosis average eight years later than the first evaluation by mental health services. Compared to males, females showed a significantly greater delay in referral to mental health services and a significantly higher age at diagnosis of ASD. Among men, diagnostic delay inversely correlated with scores on the AdAS Spectrum total, Verbal communication, Empathy and Inflexibility and adherence to routine domains. Among women, diagnostic delay positively correlated with the Attention to detail score while the age at diagnosis of ASD positively correlated with the AdAS Spectrum Verbal communication and Restricted interests and rumination domain scores. Females were less likely to be correctly diagnosed and more likely to be misdiagnosed at first evaluation than men. Females reported significantly higher scores than men in the Hyper/Hyporeactivity to sensory input domain only among subjects who were misdiagnosed. Our findings provide gender-specific information about ASD patients seeking help for comorbid conditions and might be a primary ground for future research.

Lien vers le texte intégral (Open Access ou abonnement)

9. Gevezova M, Minchev D, Pacheva I, Sbirkov Y, Yordanova R, Timova E, Kotetarov V, Ivanov I, Sarafian V. Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder. Current topics in medicinal chemistry. 2021; 21(11): 985-94.

BACKGROUND: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. INTRODUCTION: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. METHODS: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed with a Seahorse XFp analyzer. RESULTS: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. CONCLUSION: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.

Lien vers le texte intégral (Open Access ou abonnement)

10. Golovina E, Fadason T, Lints TJ, Walker C, Vickers MH, O’Sullivan JM. Understanding the impact of SNPs associated with autism spectrum disorder on biological pathways in the human fetal and adult cortex. Scientific reports. 2021; 11(1): 15867.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein-protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5 × 10(-8)) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein-protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast, in the adult cortex they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.

Lien vers le texte intégral (Open Access ou abonnement)

11. Gunning M, Pavlidis P. « Guilt by association » is not competitive with genetic association for identifying autism risk genes. Scientific reports. 2021; 11(1): 15950.

Discovering genes involved in complex human genetic disorders is a major challenge. Many have suggested that machine learning (ML) algorithms using gene networks can be used to supplement traditional genetic association-based approaches to predict or prioritize disease genes. However, questions have been raised about the utility of ML methods for this type of task due to biases within the data, and poor real-world performance. Using autism spectrum disorder (ASD) as a test case, we sought to investigate the question: can machine learning aid in the discovery of disease genes? We collected 13 published ASD gene prioritization studies and evaluated their performance using known and novel high-confidence ASD genes. We also investigated their biases towards generic gene annotations, like number of association publications. We found that ML methods which do not incorporate genetics information have limited utility for prioritization of ASD risk genes. These studies perform at a comparable level to generic measures of likelihood for the involvement of genes in any condition, and do not out-perform genetic association studies. Future efforts to discover disease genes should be focused on developing and validating statistical models for genetic association, specifically for association between rare variants and disease, rather than developing complex machine learning methods using complex heterogeneous biological data with unknown reliability.

Lien vers le texte intégral (Open Access ou abonnement)

12. Hirai M, Sakurada T, Izawa J, Ikeda T, Monden Y, Shimoizumi H, Yamagata T. Greater reliance on proprioceptive information during a reaching task with perspective manipulation among children with autism spectrum disorders. Scientific reports. 2021; 11(1): 15974.

Difficulties with visual perspective-taking among individuals with autism spectrum disorders remain poorly understood. Many studies have presumed that first-person visual input can be mentally transformed to a third-person perspective during visual perspective-taking tasks; however, existing research has not fully revealed the computational strategy used by those with autism spectrum disorders for taking another person’s perspective. In this study, we designed a novel approach to test a strategy using the opposite-directional effect among children with autism spectrum disorders. This effect refers to how a third-person perspective as a visual input alters a cognitive process. We directly manipulated participants’ visual perspective by placing a camera at different positions; participants could watch themselves from a third-person perspective during a reaching task with no endpoint feedback. During a baseline task, endpoint bias (with endpoint feedback but no visual transformation) did not differ significantly between groups. However, the endpoint was affected by extrinsic coordinate information in the control group relative to the autism spectrum disorders group when the visual perspective was transformed. These results indicate an increased reliance on proprioception during the reaching task with perspective manipulation in the autism spectrum disorders group.

Lien vers le texte intégral (Open Access ou abonnement)

13. Knott R, Johnson BP, Tiego J, Mellahn O, Finlay A, Kallady K, Kouspos M, Mohanakumar Sindhu VP, Hawi Z, Arnatkeviciute A, Chau T, Maron D, Mercieca EC, Furley K, Harris K, Williams K, Ure A, Fornito A, Gray K, Coghill D, Nicholson A, Phung D, Loth E, Mason L, Murphy D, Buitelaar J, Bellgrove MA. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology. Molecular autism. 2021; 12(1): 55.

BACKGROUND: ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has hampered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours; investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters; and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. METHODS: The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. CONCLUSION: The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures.

Lien vers le texte intégral (Open Access ou abonnement)

14. Konieczny P, Mukherjee S, Stepniak-Konieczna E, Taylor K, Niewiadomska D, Piasecka A, Walczak A, Baud A, Dohno C, Nakatani K, Sobczak K. Cyclic mismatch binding ligands interact with disease-associated CGG trinucleotide repeats in RNA and suppress their translation. Nucleic acids research. 2021; 49(16): 9479-95.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a limited expansion of CGG repeats in the FMR1 gene. Degeneration of neurons in FXTAS cell models can be triggered by accumulation of polyglycine protein (FMRpolyG), a by-product of translation initiated upstream to the repeats. Specific aims of our work included testing if naphthyridine-based molecules could (i) block FMRpolyG synthesis by binding to CGG repeats in RNA, (ii) reverse pathological alterations in affected cells and (iii) preserve the content of FMRP, translated from the same FMR1 mRNA. We demonstrate that cyclic mismatch binding ligand CMBL4c binds to RNA structure formed by CGG repeats and attenuates translation of FMRpolyG and formation of nuclear inclusions in cells transfected with vectors expressing RNA with expanded CGG repeats. Moreover, our results indicate that CMBL4c delivery can reduce FMRpolyG-mediated cytotoxicity and apoptosis. Importantly, its therapeutic potential is also observed once the inclusions are already formed. We also show that CMBL4c-driven FMRpolyG loss is accompanied by partial FMRP reduction. As complete loss of FMRP induces FXS in children, future experiments should aim at evaluation of CMBL4c therapeutic intervention in differentiated tissues, in which FMRpolyG translation inhibition might outweigh adverse effects related to FMRP depletion.

Lien vers le texte intégral (Open Access ou abonnement)

15. Mody M, Petibon Y, Han P, Kuruppu D, Ma C, Yokell D, Neelamegam R, Normandin MD, Fakhri GE, Brownell AL. In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker. Scientific reports. 2021; 11(1): 15897.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the Fragile X Mental Retardation (FMR1) gene. The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) which has been implicated in the pathogenesis of the disorder. In the present study we used the radioligand 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([(18)F]FPEB) in simultaneous PET-MR imaging of males with FXS and age- and gender-matched controls to assess the availability of mGlu5 receptors in relevant brain areas. Patients with FXS showed lower [(18)F]FPEB binding potential (p <  0.01), reflecting reduced mGluR5 availability, than the healthy controls throughout the brain, with significant group differences in insula, anterior cingulate, parahippocampal, inferior temporal and olfactory cortices, regions associated with deficits in inhibition, memory, and visuospatial processes characteristic of the disorder. The results are among the first to provide in vivo evidence of decreased availability of mGluR5 in the brain in individuals with FXS than in healthy controls. The consistent results across the subjects, despite the tremendous challenges with neuroimaging this population, highlight the robustness of the protocol and support for its use in drug occupancy studies; extending our radiotracer development and application efforts from mice to humans.

Lien vers le texte intégral (Open Access ou abonnement)

16. Narzisi A, Muccio R. A Neuro-Phenomenological Perspective on the Autism Phenotype. Brain sciences. 2021; 11(7).

In the current paper, we present a view of autism spectrum disorder (ASD) which avoids the typical relational issues, instead drawing on philosophy, in particular Husserlian phenomenology. We begin by following the recent etiological perspectives that suggest a natural predisposition of a part of individuals with ASD towards hypersensitivity and the reduced influence of cognitive priors (i.e., event schemas). Following this perspective, these two characteristics should be considered as a sort of phenomenological a priori that, importantly, could predispose people with ASD towards a spiritual experience, not intended in its religious meaning, but as an attribute of consciousness that consists of being aware of and attentive to what is occurring in the present moment. Potential clinical implications are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

17. Ni HC, Lin HY, Chen YL, Hung J, Wu CT, Wu YY, Liang HY, Chen RS, Shur-Fen Gau S, Huang YZ. 5-day Multi-Session Intermittent Theta Burst Stimulation over Bilateral Posterior Superior Temporal Sulci in Adults with Autism-a Pilot Study. Biomedical journal. 2021.

BACKGROUND: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. MATERIAL AND METHODS: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. RESULTS: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. CONCLUSIONS: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Lien vers le texte intégral (Open Access ou abonnement)

18. Podgórska-Bednarz J, Perenc L. Hyperbaric Oxygen Therapy for Children and Youth with Autism Spectrum Disorder: A Review. Brain sciences. 2021; 11(7).

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder determined by a complex of factors (genetic and environmental). On a pathophysiological basis hyperbaric oxygen therapy (HBOT) has been suggested as an effective therapeutic method in ASD, and thus many parents/guardians attempt to treat their child with ASD using this method. Therefore, this review aimed to verify the significant therapeutic value of this method for individuals with ASD. The literature review included all articles from the last 5 years (2015-2021) that met the inclusion criteria-both original papers and literature reviews. None of the 10 literature reviews indicated that HBOT was a clearly effective form of therapy in the case of ASD. Two out of four papers presenting the results of the intervention studies also did not recommend the use of this form of therapy in children with ASD. The results of the other two studies were not entirely relevant to the purpose of this review because one study had no control group, while the other study focused solely on auditory processing disorders. A review of the literature on whether HBOT as a therapy significantly affects the symptoms of ASD does not confirm its effectiveness.

Lien vers le texte intégral (Open Access ou abonnement)

19. Poeta L, Padula A, Lioi MB, van Bokhoven H, Miano MG. Analysis of a Set of KDM5C Regulatory Genes Mutated in Neurodevelopmental Disorders Identifies Temporal Coexpression Brain Signatures. Genes. 2021; 12(7).

Dysregulation of transcriptional pathways is observed in multiple forms of neurodevelopmental disorders (NDDs), such as intellectual disability (ID), epilepsy and autism spectrum disorder (ASD). We previously demonstrated that the NDD genes encoding lysine-specific demethylase 5C (KDM5C) and its transcriptional regulators Aristaless related-homeobox (ARX), PHD Finger Protein 8 (PHF8) and Zinc Finger Protein 711 (ZNF711) are functionally connected. Here, we show their relation to each other with respect to the expression levels in human and mouse datasets and in vivo mouse analysis indicating that the coexpression of these syntenic X-chromosomal genes is temporally regulated in brain areas and cellular sub-types. In co-immunoprecipitation assays, we found that the homeotic transcription factor ARX interacts with the histone demethylase PHF8, indicating that this transcriptional axis is highly intersected. Furthermore, the functional impact of pathogenic mutations of ARX, KDM5C, PHF8 and ZNF711 was tested in lymphoblastoid cell lines (LCLs) derived from children with varying levels of syndromic ID establishing the direct correlation between defects in the KDM5C-H3K4me3 pathway and ID severity. These findings reveal novel insights into epigenetic processes underpinning NDD pathogenesis and provide new avenues for assessing developmental timing and critical windows for potential treatments.

Lien vers le texte intégral (Open Access ou abonnement)

20. Pratesi CB, Garcia AB, Pratesi R, Gandolfi L, Hecht M, Nakano EY, Zandonadi RP. Quality of Life in Caregivers of Children and Adolescents with Autistic Spectrum Disorder: Development and Validation of the Questionnaire. Brain sciences. 2021; 11(7).

Studies have shown that children and adolescents with autism and their relatives present a high level of stress and more family problems, impacting parents’ and caregivers’ quality of life (QoL). Despite studies on this subject, there is no specific questionnaire to evaluate QoL in parents or caregivers of children and adolescents with an autistic spectrum disorder (ASD) in Brazil. Therefore, this study’s primary purpose was to develop and validate a specific questionnaire to evaluate QoL in these individuals. The study was performed using the following steps: development of the ASD Parent/caregiver QoL questionnaire (autistic spectrum disorder parent/caregiver quality of life-ASDPC-QoL), subjective evaluation, validation of the questionnaire by the Delphi method, assessment of internal consistency, responsiveness, and reliability of the ASLPC-QoL, and administration of the questionnaire to 881 Brazilian ASD caregivers or parents. ASDPC-QoL comprises 28 questions divided into four domains (social, concerns, physical and mental health) with good psychometric properties (reproducibility, reliability, internal consistency, responsiveness, and validity). Our data showed that worries and physical health were the domains with the lowest scores in ASDPCA-QoL. ASDPCA-QoL did not differ among gender and age of child considering the total and all domains. Older participants (≥41 y/o) presented the best scores for social and worries domains but did not differ in other domains and the total. Parents or caregivers of ASD children diagnosed for more than three years have better mental and physical health domains than those recently diagnosed (up to 1 year) but did not differ in the total and other domains. Individuals with a partner and with the highest educational level present the best score for the social domain. Employed individuals showed better scores than unemployed ones for all domains and the total, except for worries, which did not differ. It also occurred comparing the individuals that do not use antidepressants and the ones that use them. Assessing and better understanding the QoL of caregivers is highly relevant. By understanding the social, worries, physical, and emotional health domains of caregivers, it is possible to track harmful aspects, prevent and treat pathologies, in addition to assisting in the implementation of effective public policies.

Lien vers le texte intégral (Open Access ou abonnement)

21. Raja GL, Subhashree KD, Kantayya KE. In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life. Environmental research. 2022; 203: 111829.

Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants that interfere with the endocrine system, resulting in developmental malformations, reproductive disorders, and alterations to immune and nervous system function. The emergence of screening studies identifying these chemicals in fetal developmental matrices such as maternal blood, placenta and amniotic fluid has steered research focus towards elucidation of in utero effects of exposure to these chemicals, as their capacity to cross the placenta and reach the fetus was established. The presence of EDCs, a majority of which are estrogen mimics, in the fetal environment during early development could potentially affect neurodevelopment, with implications for behavioural and neurological disorders in adult life. This review summarizes studies in animal models and human cohorts that aim to elucidate mechanisms of action of EDCs in the context of neurodevelopment and disease risk in adult life. This is a significant area of study as early brain development is heavily mediated by estrogen and could be particularly sensitive to EDC exposure. A network analysis presented using genes summarized in this review, further show a significant association with disorders such as major depressive disorder, alcoholic disorder, psychotic disorders and autism spectrum disorder. Functional outcomes such as alterations in memory, behaviour, cognition, learning memory, feeding behaviour and regulation of ion transport are also highlighted. Interactions between genes, receptors and signaling pathways like NMDA glutamate receptor activity, 5-hydroxytryptamine receptor activity, Ras-activated Ca(2)(+) influx and Grin2A interactions, provide further potential mechanisms of action of EDCs in mediating brain function. Taken together with the growing pool of human and animal studies, this review summarizes current status of EDC neurotoxicity research, limitations and future directions of study for researchers.

Lien vers le texte intégral (Open Access ou abonnement)

22. Roquette Viana C, Caldeira S, Lourenço M, Simões Figueiredo A. Parenting of Children with Autism Spectrum Disorder: A Grounded Theory Study. Healthcare (Basel, Switzerland). 2021; 9(7).

BACKGROUND: Parenting a child with an autism spectrum disorder (ASD) involves several processes and emotions during this transition. In addition to the family’s natural transition when a child is born, the family of a child with ASD has to deal with the particularities of the disability, its characteristics, and its evolution. METHODS: This is a qualitative grounded theory study aiming to deepen the knowledge about the process of parenting children with ASD. Data were collected using interviews and observations of nine couples and one single mother. RESULTS: Coding and analysis led to the main theme, which is as follows: parenting of children with ASD as representative of the parents’ transformation while caring for the child, also based on adaptation throughout this experience. CONCLUSIONS: Parenting is a dynamic process, grounded on the interaction of different contexts, such as family, education, health, and society, and on the co-construction of different times and episodes. These characteristics underline the complex and individual nature of parenting children with autism, which requires specific assessments and interventions by nurses when caring for these families, whether in a family nursing context, community nursing, and pediatric nursing or midwifery.

Lien vers le texte intégral (Open Access ou abonnement)

23. Schuster S, Reece J, Florentzou A, Apos E. Treating enuresis in children with neurodevelopmental disorders using bell and pad alarm. Journal of pediatric urology. 2021; 17(5): 645.e1-.e8.

OBJECTIVE: There is a high prevalence of enuresis in children with neurodevelopmental disorders, yet research regarding treatment for this group has been neglected. The efficacy of treatment using bell and pad alarm therapy is not well reported especially in children with neurodevelopmental disorders. This study sought to compare the treatment efficacy of practitioner-assisted bell-and-pad enuresis alarm therapy for children with neurodevelopmental disorders and typically developing children. STUDY DESIGN: This study utilized the data of Apos et al. (2018), a retrospective medical record audit collected from multiple clinical settings across Australia. A total of 2986 patient records (3659 treatment records) were included. The participants were children aged 5-16 years, who were diagnosed with enuresis. Children with a neurodevelopmental disorder (n = 158) had a clinical diagnosis present in the medical history of attention deficit disorder, autism spectrum disorder, or intellectual disability. Children who indicated any of the following comorbidities were excluded: cerebral palsy, brain injury, malformation of the renal tract, previous bladder or renal surgery, spinal cord malformation, spinal cord trauma or tumor, or a neurodegenerative disorder. Treatment success was defined as ≥ 14 dry nights. Relapse was defined as one symptom recurrence per month post-interruption of treatment, as defined by the International Children’s Continence Society definitions. RESULTS: The success rate for children with neurodevelopmental disorders was 62% and typically developing children was 78%. There was no significant difference between the number of treatments received or relapse rates by those children with a neurodevelopmental disorder and typically developing children. The summary figure shows the percentage of children in each group after their first treatment who were successful (success defined as dry for ≥ 14 days), who succeeded (dry for ≥ 14 days) but then relapsed and those who showed no success. The percentage of children with no NDD who were successfully dry after the first treatment was 78%. Children with ID had success after the first treatment of 59%, the lowest of all groups analyzed. CONCLUSION: The type of alarm therapy reported in this study is effective for treating enuresis in children with neurodevelopmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

24. Siafis S, Rodolico A, Çıray O, Murphy DG, Parellada M, Arango C, Leucht S. Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder. Brain sciences. 2021; 11(7).

INTRODUCTION: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence. METHODS: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland-Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis. RESULTS: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [-8.1%, 16.74%]; no subgroup differences χ(2) = 1.24, p-value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [-0.87, 1.04]; χ(2) = 0.02, p-value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used. DISCUSSION: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed.

Lien vers le texte intégral (Open Access ou abonnement)

25. Sugino Y, Nishikawa K, Kato M, Sasaki T, Kato M, Masui S, Yoshio Y, Kanda H, Sugimura Y, Inoue T. [Initial Experience of Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumor (PDD-TURBT)]. Hinyokika kiyo Acta urologica Japonica. 2021; 67(7): 303-8.

Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (p＜0.01, McNemar’s test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.

Lien vers le texte intégral (Open Access ou abonnement)

26. Tian C, Paskus JD, Fingleton E, Roche KW, Herring BE. Autism Spectrum Disorder/Intellectual Disability-Associated Mutations in Trio Disrupt Neuroligin 1-Mediated Synaptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2021; 41(37): 7768-78.

We recently identified an autism spectrum disorder/intellectual disability (ASD/ID)-related de novo mutation hotspot in the Rac1-activating GEF1 domain of the protein Trio. Trio is a Rho guanine nucleotide exchange factor (RhoGEF) that is essential for glutamatergic synapse function. An ASD/ID-related mutation identified in Trio’s GEF1 domain, Trio D1368V, produces a pathologic increase in glutamatergic synaptogenesis, suggesting that Trio is coupled to synaptic regulatory mechanisms that govern glutamatergic synapse formation. However, the molecular mechanisms by which Trio regulates glutamatergic synapses are largely unexplored. Here, using biochemical methods, we identify an interaction between Trio and the synaptogenic protein Neuroligin 1 (NLGN1) in the brain. Molecular biological approaches were then combined with super-resolution dendritic spine imaging and whole-cell voltage-clamp electrophysiology in hippocampal slices from male and female rats to examine the impact ASD/ID-related Trio mutations have on NLGN1-mediated synaptogenesis. We find that an ASD/ID-related mutation in Trio’s eighth spectrin repeat region, Trio N1080I, inhibits Trio’s interaction with NLGN1 and prevents Trio D1368V-mediated synaptogenesis. Inhibiting Trio’s interaction with NLGN1 via Trio N1080I blocked NLGN1-mediated synaptogenesis and increases in synaptic NMDA Receptor function but not NLGN1-mediated increases in synaptic AMPA Receptor function. Finally, we show that the aberrant synaptogenesis produced by Trio D1368V is dependent on NLGN signaling. Our findings demonstrate that ASD/ID-related mutations in Trio are able to pathologically increase as well as decrease NLGN-mediated effects on glutamatergic neurotransmission, and point to an NLGN1-Trio interaction as part of a key pathway involved in ASD/ID etiology.SIGNIFICANCE STATEMENT A number of genes have been implicated in the development of autism spectrum disorder/intellectual disability (ASD/ID) in humans. It is now important to identify relationships between these genes to uncover specific cellular regulatory pathways that contribute to these disorders. In this study, we discover that two glutamatergic synapse regulatory proteins implicated in ASD/ID, Trio and Neuroligin 1, interact with one another to promote glutamatergic synaptogenesis. We also identify ASD/ID-related mutations in Trio that either inhibit or augment Neuroligin 1-mediated glutamatergic synapse formation. Together, our results identify a synaptic regulatory pathway that, when disrupted, likely contributes to the development of ASD/ID. Going forward, it will be important to determine whether this pathway represents a point of convergence of other proteins implicated in ASD/ID.

Lien vers le texte intégral (Open Access ou abonnement)

27. Unterman I, Bloch I, Cazacu S, Kazimirsky G, Ben-Zeev B, Berman BP, Brodie C, Tabach Y. Expanding the MECP2 network using comparative genomics reveals potential therapeutic targets for Rett syndrome. eLife. 2021; 10.

Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are the main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT are currently available. Here, we used an evolutionary genomics approach to construct an unbiased MECP2 gene network, using 1028 eukaryotic genomes to prioritize proteins with strong co-evolutionary signatures with MECP2. Focusing on proteins targeted by FDA-approved drugs led to three promising targets, two of which were previously linked to MECP2 function (IRAK, KEAP1) and one that was not (EPOR). The drugs targeting these three proteins (Pacritinib, DMF, and EPO) were able to rescue different phenotypes of MECP2 inactivation in cultured human neural cell types, and appeared to converge on Nuclear Factor Kappa B (NF-κB) signaling in inflammation. This study highlights the potential of comparative genomics to accelerate drug discovery, and yields potential new avenues for the treatment of RTT.

Lien vers le texte intégral (Open Access ou abonnement)

28. Valentino F, Bruno LP, Doddato G, Giliberti A, Tita R, Resciniti S, Fallerini C, Bruttini M, Lo Rizzo C, Mencarelli MA, Mari F, Pinto AM, Fava F, Baldassarri M, Fabbiani A, Lamacchia V, Benetti E, Zguro K, Furini S, Renieri A, Ariani F. Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations. Brain sciences. 2021; 11(7).

Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that « reverse phenotyping » is fundamental to enlarge the phenotypic spectra associated with specific genes.

Lien vers le texte intégral (Open Access ou abonnement)

29. Wang L, Beaman CP, Jiang C, Liu F. Perception and Production of Statement-Question Intonation in Autism Spectrum Disorder: A Developmental Investigation. Journal of autism and developmental disorders. 2021.

Prosody or « melody in speech » in autism spectrum disorder (ASD) is often perceived as atypical. This study examined perception and production of statements and questions in 84 children, adolescents and adults with and without ASD, as well as participants’ pitch direction discrimination thresholds. The results suggested that the abilities to discriminate (in both speech and music conditions), identify, and imitate statement-question intonation were intact in individuals with ASD across age cohorts. Sensitivity to pitch direction predicted performance on intonation processing in both groups, who also exhibited similar developmental changes. These findings provide evidence for shared mechanisms in pitch processing between speech and music, as well as associations between low- and high-level pitch processing and between perception and production of pitch.

Lien vers le texte intégral (Open Access ou abonnement)

30. Wilson WJ, Harper-Hill K, Armstrong R, Downing C, Perrykkad K, Rafter M, Ashburner J. A preliminary investigation of sound-field amplification as an inclusive classroom adjustment for children with and without Autism Spectrum Disorder. Journal of communication disorders. 2021; 93: 106142.

PURPOSE: This study aimed to determine if sound-field amplification (SFA) could be used as an inclusive classroom adjustment to support primary school students with and without Autism Spectrum Disorder (ASD). METHODS: A two-group, randomised controlled trial (RCT) with crossover was conducted involving 13 students with ASD (9 males, aged 7.6 to 8.4 years) and 17 typically progressing students without ASD (7 males, aged 7.6 to 9.3 years) from 10 primary schools in and near to Brisbane, Australia. Eighteen of these children had an SFA system in their classrooms in semester one and 12 in semester two of their fourth year of formal schooling (Year 3). Potential proximate benefits were assessed using teacher questionnaire and video analysis of student listening behaviours. Potential distant benefits were assessed using measures of phonological processing in quiet and in noise, attention, memory, and educational achievement. RESULTS: Potential proximate benefits were observed for all students with teachers rating student listening behaviours higher with SFA versus without SFA. Potential distant benefits were observed for students with ASD who showed greater improvements in one area of phonological processing (blending nonsense words in noise) following SFA versus no SFA. No other potential proximate or distant benefits following SFA were observed. CONCLUSIONS: SFA could be used as an inclusive classroom adjustment to support some primary school students with and without ASD by potentially putting those students in a better position to learn, but their learning must still take place over time and realistic expectations of what can reasonably be achieved by SFA alone are needed.

Lien vers le texte intégral (Open Access ou abonnement)