1. Abdi S, Tarameshlu M, Nakhostin Ansari N, Ghelichi L, Hakim Shooshtari M. The Effect of Combined Intervention on Improvement of Early Lexical Development in Minimally Verbal Children with Autism Spectrum Disorder. Medical journal of the Islamic Republic of Iran. 2023; 37: 104.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by severe communication deficits and limited and repetitive behavioral tendencies. There are several treatment approaches and methods for minimally verbal children with ASD; nonetheless, there is inconclusive evidence about how early lexical development could be improved. The present study aimed to investigate the effect of combined intervention derived from the principles of different theories-including contemporary behaviorism, schemas, sociocultural, and event representation theories-to improve early lexical development in minimally verbal children with ASD. METHODS: In this single-group pretest-posttest study, 10 children with ASD (mean age, 47.9 ± 8.3 months), including 7 boys and 3 girls, participated. Participants received 16 intervention sessions in 8 weeks. The combined intervention consisted of various methods derived from contemporary behaviorism, schemas, sociocultural, and event representation approaches. The MacArthur-Bates Communicative Development Inventory 1 (Infant form) assessed early lexical development before and after intervention and after a 2-month follow-up. The Friedman test was used to analyze the data, and pairwise comparisons were performed with the Will-Coxon test. Cohen’s d was used to investigate the effect sizes. RESULTS: Significant increases in expressive vocabulary (P < 0.001) and receptive language (P < 0.001) were seen after the end of the intervention and at the follow-up (P = 0.005). Large effect sizes were found for expressive vocabulary (d = 3.7) and receptive vocabulary (d = 2.17). CONCLUSION: This study suggests that the combination of intervention based contemporary behaviorism, schemas, sociocultural, and event representation approaches improved receptive and expressive vocabulary in minimally verbal children with ASD.

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2. Akintunde ME, Lin YP, Krakowiak P, Pessah IN, Hertz-Picciotto I, Puschner B, Ashwood P, Van de Water J. Ex vivo exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children. Brain, behavior, & immunity – health. 2023; 34: 100697.

Children on the autism spectrum have been shown to have immune dysregulation that often correlates with behavioral deficits. The role of the post-natal environment in this dysregulation is an area of active investigation. We examined the association between plasma levels of polybrominated diphenyl ether (PBDE) and immune cell function in age-matched autistic children and non-autistic controls. Plasma from children on the autism spectrum (n = 38) and typically developing controls (TD; n = 60) were analyzed for 14 major PBDE congeners. Cytokine/chemokine production was measured in peripheral blood mononuclear cell (PBMC) supernatants with and without ex vivo BDE-49 exposure. Total plasma concentration (∑(PBDE14)) and individual congener levels were also correlated with T cell function. ∑(PBDE14) did not differ between diagnostic groups but correlated with reduced immune function in children on the autism spectrum. In autistic children, IL-2 and IFN-γ production was reduced in association with several individual BDE congeners, especially BDE-49 (p = 0.001). Furthermore, when PBMCs were exposed ex vivo to BDE-49, cells from autistic children produced elevated levels of IL-6, TNF-α, IL-1β, MIP-1α and MCP-1 (p < 0.05). Therefore, despite similar plasma levels of PBDE, these data suggest that PBMC function was differentially impacted in the context of several PBDE congeners in autistic children relative to TD children where increased body burden of PBDE significantly correlated with a suppressed immune response in autistic children but not TD controls. Further, acute ex vivo exposure of PBMCs to BDE-49 stimulates an elevated cytokine response in AU cases versus a depressed response in TD controls. These data suggest that exposure to the toxicant BDE-49 differentially impacts immune cell function in autistic children relative to TD children providing evidence for an underlying association between susceptibility to PBDE exposure and immune anomalies in children on the autism spectrum.

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3. Akter R, Urme NA, Hossain KMA, Hossain T, Ahammad S, Yeasmin MH, Hossain MZ, Parvin R, Hossain MS, Zahid MA. Protocol for a randomized clinical trial comparing the efficacy of Structured Diet (SD) and Regular Therapy (RT) for adolescents with malnutrition having Autism Spectrum Disorder (ASD). PloS one. 2023; 18(11): e0292326.

BACKGROUND: Autism spectrum disorders (ASD) have a lifelong impact on behavior, communication, cognitive function, education, physical functioning, and personal, or social life. Separate studies suggest, Therapeutic and dietary interventions are effective to some extent in managing these issues. No study integrated the nutrition and therapeutic approaches and examined the outcome on disease severity, overall health, and behavioral status in ASD. The proposed study is designed to evaluate the combined effect of regular therapy (RT) and structured diet (SD) compared to the usual diet (UD) for Adolescents with ASD. METHODS: The proposed study will be a randomized clinical trial (RCT) with the assessor, therapist, and participants blinded to group allocation. Seventy ASD children with malnutrition will be enrolled in two different facilities of the Centre for the Rehabilitation of the Paralysed (CRP) between January 2023 and June 2023. Participants will be enrolled through a hospital-based randomization process from a population-based screening dataset, and with a concealed group allocation to either RT+ SD or RT+ UD group with a 1:1 ratio. The outcome measures are the Childhood Autism Rating Scale as per DSM-5 to determine the severity of ASD, Mid-upper arm circumference (MUAC), and BMI for nutritional status, and Gilliam Autism Rating Scale (GARS-2) to assess the behavioral status. Post-test will be performed after 12 weeks of intervention, and Follow-up will be taken after 6 months of post-test. PERSPECTIVES: The result of the study will contribute to the provision of a comprehensive approach to malnourished Adolescents with ASD, and manage the issues related to the severity of ASD, stereotypical behavior, and anticipated health hazards. CLINICAL TRIAL IDENTIFIER: CTRI/2022/11/047653.

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4. Alaqel SI, Alqahtani AS, Alharbi A, Althobaiti YS, Bamaga AK, Algarni MA, Almrasy AA, Almalki AH. Spectrofluorometric quantitative analysis of aripiprazole based on quenching of natural derived carbon quantum dots in spiked human plasma. Scientific reports. 2023; 13(1): 21048.

Autism spectrum disorder is a significant concern worldwide, particularly in Middle Eastern countries. Aripiprazole, a psychiatric medicine that works as a partial agonist at D(2) receptors, is often used for autism-related behavior issues in children. Monitoring the therapy of aripiprazole could enhance the safety and effectiveness of treatment for autistic individuals. The purpose of this study was to develop a highly sensitive and environmentally friendly method for analysis of aripiprazole in plasma matrix. To achieve this, water-soluble N-carbon quantum dots were produced from a natural green precursor, guava fruit, and used in fluorescence quenching spectroscopy to determine the presence of aripiprazole. The synthesized dots were analyzed and characterized using transmission electron microscopy and Fourier transform infrared spectroscopy, and they showed a strong fluorescence emission peak at 475 nm. The proposed method was validated according to ICH M10 guidelines and was shown to be highly sensitive, allowing for nanoscale determination of aripiprazole in plasma matrix. Additionally, the method was compared to a previously reported spectrophotometric method, and it was found to be more sensitive and consistent with the principles of green analytical chemistry.

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5. Al-Bishri WM. Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis. Saudi journal of biological sciences. 2023; 30(12): 103849.

The neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-inducible factor 1 α (HIF-1 α), heat shock protein 70 (HSP-70), interleukin-17A (IL-17A), IL-35, vitamin D3 (VITD), glucose transporter-1 (GUT1), and AMP-activated protein kinase (AMPK) were estimated in Saudi ASD children versus age-matched neurotypical controls, aiming to investigate whether these parameters have potential roles in the pathophysiologic mechanisms of ASD and hoping to find a reliable marker for early ASD diagnosis. This study included 25 ASD children and 25 typically developing children (3-11 years old). The diagnosis of ASD cases was made based on the Autism Diagnostic Observation Schedule (ADOS) and the Statistical Manual of Mental Disorders (DSM-5). ASD subjects were commonly male and revealed an intelligence quotient (IQ) < 70.The results detected that ASD children have remarkable greater serum levels of nitrosative stress (3-NT), hypoxia (HIF-1 α), inflammatory (HSP-70, IL-17A, and AMPK) biomarkers and lower serum levels of anti-inflammatory (IL-35 and VITD) and metabolic stress (GUT-1) biomarkers versus age-matched controls (P ≤ 0.0001). Pearson's correlation study revealed that 3-NT was positively associated with HIF-1 α and HSP-70. HIF-1 α was also positively correlated with HSP-70. AMPK was positively associated with GUT-1, however, IL-17A was negatively correlated with IL-35 and VITD.Limitation:No specific therapeuticdrugs were administered in this study, and further studies are required to confirm the role of the selected biomarkers in ASD managements. CONCLUSION: Changes in concentrations of different biomarkers indicate that they are involved in oxidative stress, metabolic stress, immune dysregulation and ASD pathogenesis. Hence, these parameters can prove to be promising biomarkers as well as therapeutic targets for the timely diagnosis and treatment of ASD patients.

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6. Alhaddad AY, So WC, Cabibihan JJ, Bonarini A. Editorial: Technologies to support the diagnosis and therapy of individuals with autism. Frontiers in psychiatry. 2023; 14: 1304178.

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7. Alhasan A, Caruana N. Evidence for the adaptive parsing of non-communicative eye movements during joint attention interactions. PeerJ. 2023; 11: e16363.

During social interactions, the ability to detect and respond to gaze-based joint attention bids often involves the evaluation of non-communicative eye movements. However, very little is known about how much humans are able to track and parse spatial information from these non-communicative eye movements over time, and the extent to which this influences joint attention outcomes. This was investigated in the current study using an interactive computer-based joint attention game. Using a fully within-subjects design, we specifically examined whether participants were quicker to respond to communicative joint attention bids that followed predictive, as opposed to random or no, non-communicative gaze behaviour. Our results suggest that in complex, dynamic tasks, people adaptively use and dismiss non-communicative gaze information depending on whether it informs the locus of an upcoming joint attention bid. We also went further to examine the extent to which this ability to track dynamic spatial information was specific to processing gaze information. This was achieved by comparing performance to a closely matched non-social task where eye gaze cues were replaced with dynamic arrow stimuli. Whilst we found that people are also able to track and use dynamic non-social information from arrows, there was clear evidence for a relative advantage for tracking gaze cues during social interactions. The implications of these findings for social neuroscience and autism research are discussed.

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8. Almars AM, Badawy M, Elhosseini MA. ASD(2)-TL∗ GTO: Autism spectrum disorders detection via transfer learning with gorilla troops optimizer framework. Heliyon. 2023; 9(11): e21530.

Autism Spectrum Disorder (ASD) treatment requires accurate diagnosis and effective rehabilitation. Artificial intelligence (AI) techniques in medical diagnosis and rehabilitation can aid doctors in detecting a wide range of diseases more effectively. Nevertheless, due to its highly heterogeneous symptoms and complicated nature, ASD diagnostics continues to be a challenge for researchers. This study introduces an intelligent system based on the Artificial Gorilla Troops Optimizer (GTO) metaheuristic optimizer to detect ASD using Deep Learning and Machine Learning. Kaggle and UCI ML Repository are the data sources used in this study. The first dataset is the Autistic Children Data Set, which contains 3,374 facial images of children divided into Autistic and Non-Autistic categories. The second dataset is a compilation of data from three numerical repositories: (1) Autism Screening Adults, (2) Autistic Spectrum Disorder Screening Data for Adolescents, and (3) Autistic Spectrum Disorder Screening Data for Children. When it comes to image dataset experiments, the most notable results are (1) a TF learning ratio greater than or equal to 50 is recommended, (2) all models recommend data augmentation, and (3) the DenseNet169 model reports the lowest loss value of 0.512. Concerning the numeric dataset, five experiments recommend standardization and the final five attributes are optional in the classification process. The performance metrics demonstrate the worthiness of the proposed feature selection technique using GTO more than counterparts in the literature review.

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9. Arenella M, Fanelli G, Kiemeney LA, McAlonan G, Murphy DG, Bralten J. Genetic relationship between the immune system and autism. Brain, behavior, & immunity – health. 2023; 34: 100698.

Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined; however, it includes a strong genetic component and there is increasing evidence to support a role of immune dysregulation. Nonetheless, it is unclear which immune phenotypes link to ASD through genetics. Hence, we investigated the genetic correlation between ASD and diverse classes of immune conditions and markers; and if these immune-related genetic factors link to specific autistic-like traits in the population. We estimated global and local genetic correlations between ASD (n = 55,420) and 11 immune phenotypes (n = 14,256-755,406) using genome-wide association study summary statistics. Subsequently, polygenic scores (PGS) for these immune phenotypes were calculated in a population-based sample (n = 2487) and associated to five autistic-like traits (i.e., attention to detail, childhood behaviour, imagination, rigidity, social skills), and a total autistic-like traits score. Sex-stratified PGS analyses were also performed. At the genome-wide level, ASD was positively correlated with allergic diseases (ALG), and negatively correlated with lymphocyte count, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) (FDR-p = 0.01-0.02). At the local genetic level, ASD was correlated with RA, C-reactive protein, and granulocytes and lymphocyte counts (p = 5.8 × 10(-6)-0.002). In the general population sample, increased genetic liability for SLE, RA, ALG, and lymphocyte levels, captured by PGS, was associated with the total autistic score and with rigidity and childhood behaviour (FDR-p = 0.03). In conclusion, we demonstrated a genetic relationship between ASD and immunity that depends on the type of immune phenotype considered; some increase likelihood whereas others may potentially help build resilience. Also, this relationship may be restricted to specific genetic loci and link to specific autistic dimensions (e.g., rigidity).

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10. Askri W, Bouden A. Editorial: Reviews in psychiatry 2022: child and adolescent autism. Frontiers in psychiatry. 2023; 14: 1317073.

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11. Bjørklund G, Semenova Y, El-Ansary A, Al-Ayadhi LY. Porphyrinuria in Autism Spectrum Disorder: A Review. Current medicinal chemistry. 2023.

Numerous studies demonstrated that the number of children with autism spectrum disorder (ASD) has increased remarkably in the past decade. A portion of ASD etiology, however, is attributed to environmental issues and genetic disorders. We highlighted a scoping review to principally evaluate the current information on mercury exposure in ASD children and to reveal knowledge gaps. Elevated porphyrins concentration in the urinary system related to mercury exposure, such as precoproporphyrin (prcP), coproporphyrin (cP), and pentacarboxyporphyrin (5cxP), was shown in comparison with controls. Moreover, high levels of urinary porphyrins have been elevated in response to heavy metal exposure. The related pattern (increased prcP, cP, and 5cxP) with Hg exposure may be used as biomarkers in the characteristics of ASD symptoms. However, this review highlighted the data gaps because the control groups were not genderand age-matched for ASD children.

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12. Chen CC, Lin CH, Lin MC. Maternal autoimmune disease and risk of offspring autism spectrum disorder – a nationwide population-based cohort study. Frontiers in psychiatry. 2023; 14: 1254453.

INTRODUCTION: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which cause long term social and behavior impairment, and its prevalence is on the rise. Studies about the association between maternal autoimmune diseases and offspring ASD have controversial results. The aim of this study was to investigate whether maternal autoimmune diseases increase the risk of ASD in offspring from a population-based perspective. METHODS: The data sources were Taiwan’s National Health Insurance Research Database (NHIRD) and Taiwan’s Maternal and Child Health Database (MCHD), which were integrated and used to identify newborns whose mothers were diagnosed with autoimmune disease. Newborns were matched by maternal age, neonatal gender, and date of birth with controls whose mothers were without autoimmune disease using a ratio of 1:4 between 2004 and 2019. Data on diagnoses of autoimmune disease and autism spectrum disorders were retrieved from NHIRD. Patients who had at least 3 outpatient visits or at least 1 admission with a diagnosis of autoimmune disease and autism spectrum disorders were defined as incidence cases. The risks of ASD in offspring were compared between mothers with or without autoimmune disorders. RESULTS: We identified 20,865 newborns whose mothers had been diagnosed with autoimmune disease before pregnancy and matched them at a ratio of 1:4 with a total of 83,460 newborn whose mothers were without autoimmune disease, by maternal age, neonatal gender, and date of birth. They were randomly selected as the control group. The cumulative incidence rates of autism spectrum disorders (ASD) were significantly higher among the offspring of mothers with autoimmune diseases. After adjusting for cofactors, the risk of ASD remained significantly higher in children whose mother had autoimmune diseases. Regarding to specific maternal autoimmune disease, Sjögren’s syndrome and rheumatoid arthritis were both associated with elevated risks of ASD in offspring. CONCLUSION: Mother with autoimmune disease might be associated with increasing the risk of autism spectrum disorder in offspring.

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13. Chladek M, Burbridge C, Gibbons E, Willgoss T, Smith J, Clinch S. Qualitative Exploration in Exit Interviews of Changes Observed in Clinical Trials for Individuals with Autism Spectrum Disorder Without Intellectual Disability. Patient related outcome measures. 2023; 14: 313-35.

PURPOSE: To explore, from the perspective of Study Partners (SPs; eg, caregivers) of clinical trial participants with autism spectrum disorder (ASD), any changes experienced in socialization and communication over the clinical trial, how these changes manifested, and the impact these changes had on the autistic individual, the SP, and family. This helps interpret whether changes in trial outcomes were meaningful. PATIENTS AND METHODS: Interviews were conducted with the SPs of individuals with ASD, without intellectual disability, from 2 clinical trials: 86 children (aged 5-12 years) or adolescents (aged 13-17 years) who took part in the aV1ation trial (83.7% male), and 41 adults (aged 18+ years) who took part in the V1aduct trial (80.5% male). The primary endpoint for both trials was change from baseline in the Vineland(TM)-II two-domain composite, consisting of the mean of the Socialization and Communication domains. In these interviews the participants verbally indicated level of change for each of these key domains on 7-point change scales. RESULTS: Improvements in the Socialization domain enabled greater awareness of the feelings of others and allowed for stronger empathy and kindness. Improvements in the Communication domain allowed for the autistic individual to be better at listening and better at self-expression. Together, changes in these two domains, which were considered most important, allowed for richer, deeper relationships. Study Partners noted that improvements in these domains allowed for better integration within the family unit, decreased stress, and increased optimism about the autistic individual’s future. CONCLUSIONS: The impacts of changes in either domain were synergistic, combining together to create positive experiences which in turn led to further positive impacts in other skills. These qualitative insights provide context to the changes that were observed during the clinical trial and captured using the Vineland(TM)-II, illustrating the meaning of these changes to the individuals with ASD without intellectual disability and their families, and the impact that they have on people’s everyday lives and overall health-related quality of life.

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14. Chojnacka M, Beroun A, Magnowska M, Stawikowska A, Cysewski D, Milek J, Dziembowska M, Kuzniewska B. Impaired synaptic incorporation of AMPA receptors in a mouse model of fragile X syndrome. Frontiers in molecular neuroscience. 2023; 16: 1258615.

Fragile X syndrome (FXS) is the most common monogenetic cause of inherited intellectual disability and autism in humans. One of the well-characterized molecular phenotypes of Fmr1 KO mice, a model of FXS, is increased translation of synaptic proteins. Although this upregulation stabilizes in adulthood, abnormalities during the critical period of plasticity have long-term effects on circuit formation and synaptic properties. Using high-resolution quantitative proteomics of synaptoneurosomes isolated from the adult, developed brains of Fmr1 KO mice, we show a differential abundance of proteins regulating the postsynaptic receptor activity of glutamatergic synapses. We investigated the AMPA receptor composition and shuttling in adult Fmr1 KO and WT mice using a variety of complementary experimental strategies such as surface protein crosslinking, immunostaining of surface receptors, and electrophysiology. We discovered that the activity-dependent synaptic delivery of AMPARs is impaired in adult Fmr1 KO mice. Furthermore, we show that Fmr1 KO synaptic AMPARs contain more GluA2 subunits that can be interpreted as a switch in the synaptic AMPAR subtype toward an increased number of Ca(2+-)impermeable receptors in adult Fmr1 KO synapses.

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15. Clinch S, Hudgens S, Gibbons E, Willgoss T, Smith J, Polek E, Burbridge C. Quantitative and Qualitative Exploration of Meaningful Change on the Vineland Adaptive Behavior Scales (Vineland™-II) in Children and Adolescents with Autism Without Intellectual Disability Following Participation in a Clinical Trial. Patient related outcome measures. 2023; 14: 337-54.

PURPOSE: The Vineland(TM) Adaptive Behavior Scale is often used in autism spectrum disorder (ASD) trials. The Adaptive Behavior Composite Score (VABS-ABC) is the standardized overall score (the average of the Socialization, Communication and Daily Living skills domains), and the standardized 2-Domain Composite Score (VABS-2DC) is a novel outcome measure (average of the Socialization and Communication domains). A within-person meaningful change threshold (MCT) has not been established for the VABS-2DC. This paper presents a quantitative and qualitative interpretation of what constitutes a meaningful change in these scores to individuals with ASD without Intellectual Disability (ID; IQ≥70) and their families, as reported by their study partners (SPs). PARTICIPANTS AND METHODS: Data were obtained from the aV1ation clinical trial in children and adolescents with ASD and associated exit interviews. The intent-to-treat (ITT) clinical trial population included 308 individuals with autism (85.4% male; average age: 12.4 years [standard deviation (SD)=2.97]); 124 in the child cohort (aged 5 to 12 years; average age: 9.4 years [SD=1.86]), and 184 in the adolescent cohort (aged 13 to 17 years; average age: 14.5 years [SD=1.39]). Study partners of 86 trial participants were included in the Exit Interview Population (EIP): participants represented were 83.7% male, average age: 12.3 years [SD=2.98]). Anchor and distribution-based methods were used to estimate within-person change to support a responder definition, to aid interpretation of the clinical trial data; qualitative data were used to contextualize the meaning of changes observed. RESULTS: A within-person MCT range of 4 to 8 points was proposed for both VABS-ABC and VABS-2DC, which was associated with at least a 1-point improvement on 4 different anchors. Evidence for this within-person MCT was further supported by qualitative data, which suggested any change was considered meaningful to the individual with ASD, as reported by their SP, no matter what the magnitude. CONCLUSION: A change in standardized score of 4 to 8 points constitutes a within-person MCT on both VABS-ABC and novel VABS-2DC in those with ASD and no ID. A change of this, or more, was reported by the SPs in this trial to be meaningful and highly impactful upon the individuals with ASD and their family.

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16. Cording KR, Bateup HS. Altered motor learning and coordination in mouse models of autism spectrum disorder. Frontiers in cellular neuroscience. 2023; 17: 1270489.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing prevalence. Over 1,000 risk genes have now been implicated in ASD, suggesting diverse etiology. However, the diagnostic criteria for the disorder still comprise two major behavioral domains – deficits in social communication and interaction, and the presence of restricted and repetitive patterns of behavior (RRBs). The RRBs associated with ASD include both stereotyped repetitive movements and other motor manifestations including changes in gait, balance, coordination, and motor skill learning. In recent years, the striatum, the primary input center of the basal ganglia, has been implicated in these ASD-associated motor behaviors, due to the striatum’s role in action selection, motor learning, and habit formation. Numerous mouse models with mutations in ASD risk genes have been developed and shown to have alterations in ASD-relevant behaviors. One commonly used assay, the accelerating rotarod, allows for assessment of both basic motor coordination and motor skill learning. In this corticostriatal-dependent task, mice walk on a rotating rod that gradually increases in speed. In the extended version of this task, mice engage striatal-dependent learning mechanisms to optimize their motor routine and stay on the rod for longer periods. This review summarizes the findings of studies examining rotarod performance across a range of ASD mouse models, and the resulting implications for the involvement of striatal circuits in ASD-related motor behaviors. While performance in this task is not uniform across mouse models, there is a cohort of models that show increased rotarod performance. A growing number of studies suggest that this increased propensity to learn a fixed motor routine may reflect a common enhancement of corticostriatal drive across a subset of mice with mutations in ASD-risk genes.

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17. Davidson D, Morales D. Reducing stigma toward autistic peers: a pilot investigation of a virtual autism acceptance program for children. Frontiers in psychiatry. 2023; 14: 1241487.

Inclusive educational practices can be beneficial for autistic children, especially when the general education classroom can better meet the child’s academic and socio-emotional needs than a special education classroom. Unfortunately, autistic children may not thrive in general education classrooms if they are perceived negatively, subject to bullying, and are socially isolated and rejected by their typically developing peers. Autism acceptance programs may help address the root cause of these problems, autism stigma. Thus, this study evaluated the effectiveness of a virtual autism acceptance program presented to typically developing, 8-10-year-old children through remote learning technology. The 5-week, stakeholder-approved pilot program included a themed module each week (e.g., facts about autism and reducing stigma, sensory sensitivities, strengths of those with autism) presented through a variety of online educational materials. Pretest, posttest, and maintenance results showed that the program was effective in improving children’s knowledge about autism, and children’s attitudes and behavioral intentions toward their peers with autism. In addition to reducing autism stigma, study findings suggest that remote learning and virtual tools can be used to implement an efficacious autism acceptance program to children, allowing for greater and more cost-effective outreach to children and schools.

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18. de Lange S, Muller D, Dafkin C. The relationship between balance and urinary cortisol and neopterin in autistic children. Comprehensive psychoneuroendocrinology. 2023; 16: 100216.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by stereotyped behavior, restricted interests and social/communicative deficits. The physiological etiology of ASD is not currently understood, however recent research has implicated dysregulation of the immune system as a central feature. The interplay between the stress systems, the immune system and the brain has been well-documented and implicated in other psychiatric and neurological disorders. This interplay suggests a role for the hypothalamic-pituitary-adrenal (HPA) axis in the etiology of ASD. We assessed levels of urinary cortisol and neopterin as markers of immune function and HPA activation in a cohort of 50 children from the central Johannesburg region. Additionally, we used the Autism Treatment Evaluation Checklist to assess autistic symptomatology and the Bruininks-Oseretsky Motor Proficiency Test (Second Edition) (BOT-2) to assess motor skills. No relationships were found between cortisol and autistic symptomatology. No relationships were found between neopterin and any of the other measures. However, a relationship was observed between urinary cortisol and performance on balance-related tasks from the BOT-2 (P < 0.05). Our findings support a theory of neurological interconnectedness between postural modulation and activation of the stress system, which has not previously been documented in children with ASD.

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19. Donoso J, Rattray F, de Bildt A, Tillmann J, Williams P, Absoud M, Totsika V. Association of cognitive and adaptive skills with internalizing and externalizing problems in autistic children and adolescents. Autism research : official journal of the International Society for Autism Research. 2023.

The presence of an intellectual disability (ID) alongside autism is considered to increase the risk for mental health and behavior problems in children and adolescents. Existing evidence is restricted by looking at ID as a categorical classification. The study aimed to examine the association of cognitive and adaptive behavior skills with internalizing and externalizing problems in a large sample of autistic children and adolescents, across a wide range of cognitive skills. Participants were 2759 children and adolescents aged between 4 and 18 years recruited as part of the Simons Simplex Collection (SSC), of whom 709 (approximately 25%) had ID. Multiple regression models examined associations of internalizing and externalizing problems with cognitive and adaptive skills (communication, daily living, and socialization skills). Cognitive skills were not associated with externalizing problems but were associated with more internalizing problems in autistic children without ID (Cog β: 0.126). All adaptive skill domains were inversely associated with externalizing (Communication β: -0.145; Daily-Living β: -0.132; Socialization β: -0.289) and internalizing problems (Communication β: -0.074; Daily-Living β: -0.064; Socialization β: -0.213) in those without ID. Daily living (β: -0.158) and socialization skills (β: -0.104) were inversely correlated with externalizing problems in autistic children with ID, while only socialization problems (β: -0.099) were associated with internalizing problems in this group. Socialization skills were systematically associated with internalizing and externalizing problems across all levels of cognitive functioning. Supporting social skills development may benefit all aspects of child mental health, while recognizing that children with higher cognitive skills are more vulnerable to internalizing problems might assist with earlier identification of these problems.

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20. Elangovan P, Ramasamy G, Sundaram M, Ramasamy M. Efficacy of Siddha Therapeutics on Mantha Sanni (Autism Spectrum Disorder) Among Pediatric Patients: An Interventional Non-randomized Open-Label Clinical Trial. Cureus. 2023; 15(10): e47128.

BACKGROUND: Autism Spectrum Disorder (ASD) refers to a collection of neurodevelopmental disorders that affect brain development and can lead to various psychological imbalances in caregivers of affected children. Siddha formulations have been shown to have a role beyond the physical body and play a significant role in managing Mantha sannior ASD. The objective of this study was to examine the impacts of Amukkara chooranam and Yegamooli thylam in the pediatric population diagnosed with ASD. METHODS: This was a prospective, interventional, non-randomized, open clinical trial involving 30 patients who met the inclusion and exclusion criteria. Patients received Amukkara chooranam at a dose of 300 mg for ages 3-4 years, 500 mg for ages 5-7 years, and 1 gm for ages 8-12 years, twice a day with honey for 90 days, and Yegamooli thylam was administered using the Thuvalai external manipulation technique once a day for 90 days. Scoring by the Indian Scale for Assessment of Autism (ISAA) was documented at the end of the 0th day, 45th day, and 90th day. RESULTS: The scores were compared at each follow-up, and a statistically significant difference was found at the end of the 90th day of treatment with Amukkara chooranam and Yegamooli thylam (P < 0.05). The statistical analysis included calculating the mean and standard deviation of the clinical assessment, parameters both before and after the treatment were 37.66667 ±13.82485. CONCLUSION: The treatment with Amukkara chooranam and Yegamooli thylam resulted in a clinically significant improvement in clinical assessment parameters in children with ASD.

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21. Gómez-Campos R, Vidal Espinoza R, Castro-Fuentes C, Flores-Vergara S, Gálvez-Zurita J, Urra-Albornoz C, la Torre Choque C, Bolaños MC. Comparison of social isolation in autistic children and adolescents according to age, marital status and number of siblings. Journal of education and health promotion. 2023; 12: 316.

BACKGROUND: Children and adolescents with autism spectrum disorder (ASD) have difficulties that limit their opportunities to interact with peers and family members. These behaviors can lead to social exclusion, and consequently social isolation. The aim was to compare social isolation of children and adolescents with ASD according to age, marital status, and number of siblings. MATERIALS AND METHODS: Cross-sectional descriptive study in 37 subjects with ASD. Social isolation was assessed using a 6-item scale (with five alternatives). The sociodemographic variables were age, sex, marital status of parents, and number of siblings. Two groups were formed according to age (children from 4 to 10 years old and adolescents from 11 to 20 years old). RESULTS: For the total score of the social isolation scale, children showed a higher score (21.1 ± 4.7) than adolescents (17.7 ± 5.7). Children living with divorced parents had lower scores (16.2 ± 3.6), compared to married (22.2 ± 4.5) and cohabiting (22.8) children. For the number of siblings, with no siblings 17.2 ± 3.1 points, one sibling 22.2 ± 3.5 points, two siblings 22.1 ± 3.1 points, and three siblings 22.4 ± 3.2 points (P < 0.05). Age was related to social isolation (r = -0.30, P < 0.05). CONCLUSION: Children who live with divorced parents and have no siblings presented a higher degree of isolation in relation to their counterparts who live with both parents and have at least one sibling. Age plays a relevant role, with children aged 4-10 years presenting a lower degree of isolation than the adolescent group. It is suggested that the preservation of a functional family and the presence of siblings could contribute to improving social isolation.

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22. Greenberg RL, Guzick AG, Schneider SC, Weinzimmer SA, Kook M, Perozo Garcia AB, Storch EA. Depressive Symptoms in Autistic Youth with Anxiety Disorders. Journal of developmental and behavioral pediatrics : JDBP. 2023; 44(9): e597-e603.

OBJECTIVE: Anxiety and depression often coexist in youth and share overlapping symptomatology; however, little is known about the comorbidity of anxiety and depression in autistic youth. This study explores (1) the frequency of depressive symptoms among autistic children with clinically significant anxiety, (2) clinical variables that may be associated with elevated depressive symptoms, and (3) whether pretreatment depressive symptoms predict cognitive behavioral therapy (CBT) outcomes for anxiety. METHOD: Children aged 7 to 13 years (N = 87) and their parents participated in a randomized controlled trial comparing 2 versions of a parent-led, telehealth-delivered CBT program. Parents and children completed a variety of clinical assessments and self-report questionnaires before and after treatment. RESULTS: Fifty-seven percent of the child sample reported experiencing elevated depressive symptoms while roughly 20% of parents reported elevated depressive symptoms in their child. A strong association between anxiety and depression was found. Heightened feelings of loneliness, per child report, and functional impairment, per parent report, were found to be uniquely associated with elevated depressive symptoms. Finally, depressive symptoms were not a significant predictor of CBT outcomes for anxiety. CONCLUSION: Findings suggest high degrees of comorbidity between anxiety and depression among autistic children and that feelings of loneliness, anxiety, and functional impairment may be early indicators of mood-related concerns. Further research is needed to determine the full extent of the association between anxiety and depression and additional options for treating depression in autistic children.

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23. Gupta V, Ben-Mahmoud A, Ku B, Velayutham D, Jan Z, Yousef Aden A, Kubbar A, Alshaban F, Stanton LW, Jithesh PV, Layman LC, Kim HG. Identification of two novel autism genes, TRPC4 and SCFD2, in Qatar simplex families through exome sequencing. Frontiers in psychiatry. 2023; 14: 1251884.

This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of de novo and homozygous missense and splice variants. Multiple individuals displayed more than one candidate variant, suggesting the potential involvement of digenic or oligogenic models. These variants were absent in the Genome Aggregation Database (gnomAD) and exhibited extremely low frequencies in the local control population dataset. Two novel autism genes, TRPC4 and SCFD2, were discovered in two Qatari autism individuals. Furthermore, the D651A substitution in CLCN3 and the splice acceptor variant in DHX30 were identified as likely deleterious mutations. Protein modeling was utilized to evaluate the potential impact of three missense variants in DEAF1, CLCN3, and SCFD2 on their respective structures and functions, which strongly supported the pathogenic natures of these variants. The presence of multiple de novo mutations across trios underscored the significant contribution of de novo mutations to the genetic etiology of ASD. Functional assays and further investigations are necessary to confirm the pathogenicity of the identified genes and determine their significance in ASD. Overall, this study sheds light on the genetic factors underlying ASD in Qatar and highlights the importance of considering diverse populations in ASD research.

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24. Hermans RA, Storm AEM, Kloosterboer SM, Hillegers MHJ, Koch BCP, Dierckx B, de Winter BCM. Therapeutic Drug Monitoring to Optimize Risperidone Treatment in Children with Autism Spectrum Disorder. Therapeutic drug monitoring. 2023.

BACKGROUND: Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated. METHODS: In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model implemented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment. RESULTS: A risperidone sum trough target range of 3.5-7.0 mcg/L would minimize increase in body mass index z-score and optimize effectiveness. Dosing advice using TDM and a population PK model would lead to a larger proportion of children achieving the target concentration range (62.5% versus 16.7%). CONCLUSIONS: TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder.

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25. Hua Z, Hu J, Zeng H, Li J, Cao Y, Gan Y. Auditory language comprehension among children and adolescents with autism spectrum disorder: An ALE meta-analysis of fMRI studies. Autism research : official journal of the International Society for Autism Research. 2023.

Difficulties in auditory language comprehension are common among children and adolescents with autism spectrum disorder. However, findings regarding the underlying neural mechanisms remain mixed, and few studies have systematically explored the overall patterns of these findings. Therefore, this study aims to systematically review and meta-analyze the functional magnetic resonance imaging evidence of neural activation patterns while engaging in auditory language comprehension tasks among children and adolescents with autism. Using activation likelihood estimation, we conducted a series of meta-analyses to investigate neural activation patterns during auditory language comprehension tasks compared to baseline conditions in autism and non-autism groups and compared the activation patterns of the groups, respectively. Eight studies were included in the within-group analyses, and seven were included in the between-group analysis. The within-group analyses revealed that the bilateral superior temporal gyrus was activated during auditory language comprehension tasks in both groups, whereas the left superior frontal gyrus and dorsal medial prefrontal cortex were activated only in the non-autism group. Furthermore, the between-group analysis showed that children and adolescents with autism, compared to those without autism, showed reduced activation in the right superior temporal gyrus, left middle temporal gyrus, and insula, whereas the autism group did not show increased activation in any of the regions relative to the non-autism group. Overall, these findings contribute to our understanding of the potential neural mechanisms underlying difficulties in auditory language comprehension in children and adolescents with autism and provide practical implications for early screening and language-related interventions for children and adolescents with autism.

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26. Hus Y. Frozen in Time, a Focused Review of Autism Prevalence in Canadian Indigenous Communities. Neuropsychiatric disease and treatment. 2023; 19: 2451-68.

The unprecedented global continuous rise in autism prevalence is often referred to as a Pandemic while its parallel cost increase to society portrays a Tsunami. Autism data originates mostly from industrialized High-Income geopolitical regions in Europe, North America, and Asian regions. Although efforts to determine autism data from regions in Low and Mid-economies are ongoing, prevalence information from geographically remote and economically vulnerable communities within the privileged regions is largely undetermined, as is the case of the Canadian Indigenous communities, the First Nations, Inuit, and Métis highlighted in this focused review. The underlying theoretical approach adopted here is Transcultural Psychiatry with its emphasis on Context including sociopolitical circumstances, considered the gateway to understanding health, illness, and recovery in groups and individuals. Accordingly, the review includes a concise relevant government system description and history of the relations with Indigenous peoples to provide context to present indigenous relations to Canadian government agencies. Scores in these communities face a myriad of survival challenges encompassing meagre health resources and services. Establishing autism prevalence data in these communities are exceedingly difficult due to multiple factors. While prominent among them are their strong ties to traditional approaches to health, illness, and autism conceptualization, the crucial obstacle is Crown and Provincial government authorities’ and agencies’ historically rooted colonial response to the needs of families with autistic members. It embodies a posture of infantilization, an attitude that is « frozen in time » in the approach, practice, accommodations, and services for these families. The review provides the preferred autism terminology, information sources, article flow, and Future Directions, all found in the Introduction’s first paragraphs.

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27. Isogami H, Murata T, Imaizumi K, Fukuda T, Kanno A, Kyozuka H, Yasuda S, Yamaguchi A, Sato A, Ogata Y, Horiuchi S, Shinohara R, Shinoki K, Hosoya M, Yasumura S, Yamagata Z, Hashimoto K, Fujimori K, Nishigori H. Association of Preconception or Antepartum Maternal Intimate Partner Violence with Autism Spectrum Disorder in 3-Year-Old Offspring: The Japan Environment and Children’s Study. Journal of women’s health (2002). 2023.

Objective: We investigated the association between maternal antepartum intimate partner violence (IPV) and autism spectrum disorder (ASD) in 3-year-old offspring. Materials and Methods: Secondary analysis of the Japan Environment and Children’s Study, a nationwide prospective birth-cohort study, for preconceptional and antepartum psychological/physical IPV against mothers was undertaken based on data obtained from a maternal self-report questionnaire. Subgroup analysis by four-level IPV frequency versus no IPV was conducted, and the incidence of ASD diagnosed during ages 2-3 years was estimated using self-reported questionnaire data of participants from when the child was 3 years old. Multivariate logistic regression was used to determine the association of preconceptional/antepartum IPV with ASD in 3-year-old offspring. Results: Among 79,324 offspring, 355 (0.45%) had ASD; preconceptionally and prenatally, 1,504 (1.9%) and 839 (1.1%) mothers were exposed to physical IPV whereas 9,162 (11.6%) and 10,240 (12.9%) mothers were exposed to psychological IPV, respectively. Multivariate logistic regression revealed a significant association of preconceptional physical IPV with ASD in offspring (adjusted odds ratio, 3.21; 95% confidence interval, 1.24-8.31), but not for antepartum physical IPV and preconceptional and antepartum psychological IPV. Conclusion: Preconceptional, but not antepartum, physical IPV was associated with ASD in 3-year-old offspring. Preconceptional and antepartum psychological IPV was unassociated with ASD in 3-year-old offspring. Preconceptional care through prevention of preconceptional physical IPV is important for neurodevelopment in offspring, and the mechanisms underlying the effects of IPV among nonpregnant individuals on ASD development in offspring should be elucidated.

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28. Kasahara S, Kanda S, Takahashi M, Fujioka M, Morita T, Matsudaira K, Sato N, Hattori M, Momose T, Niwa SI, Uchida K. Case Report: Guanfacine and methylphenidate improved chronic lower back pain in autosomal dominant polycystic kidney disease with comorbid attention deficit hyperactivity disorder and autism spectrum disorder. Frontiers in pediatrics. 2023; 11: 1283823.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by the bilateral development of multiple cysts in the kidneys. Pain management is a clinically important issue, especially because approximately 60% of patients with ADPKD experience chronic pain related to hemorrhage from renal cysts, which significantly reduces their daily life. The cystic fibrosis transmembrane conductance regulator, the molecule responsible for cyst formation in ADPKD, is also the cause of cystic fibrosis. Since attention deficit hyperactivity disorder (ADHD) is known to occur frequently in conjunction with cystic fibrosis, ADPKD may be associated with ADHD. However, to our knowledge, no study has investigated 1) ADHD or autism spectrum disorder (ASD) as comorbidities with ADPKD, 2) the effects of ADHD medications on chronic pain in ADPKD, or 3) cerebral blood flow corresponding to guanfacine (GF) or methylphenidate (MP) treatment for chronic pain. We report the case of a 15-year-old girl with ADPKD, who had chronic back pain associated with ADPKD and had to withdraw from high school because the pain interfered with her daily life. Although she took antihypertensive medications to prevent bleeding, they did not provide adequate blood pressure control. The patient was referred to a child psychiatrist and diagnosed with ASD; however, the pain did not improve. Subsequently, she was referred to our pain center. The diagnosis of ADHD was confirmed and treatment with ADHD medications was initiated. Monotherapy with MP, atomoxetine, and GF resulted in hypertension and hypotension as side effects; however, a combination of MP 18 mg and GF 4 mg provided pain relief and moderate blood pressure control, and the patient was able to go on to college. During the course of treatment, there was an improvement in the distribution of cerebral blood flow in the prefrontal and insular cortices. Confirmation of an ADHD diagnosis comorbid with ASD enabled the use of ADHD medications. The combination of MP and GF improved chronic back pain and high blood pressure due to ADPKD and cerebral blood flow. Screening for ADHD is important in the treatment of ADPKD.

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29. Katti H, Valiyamattam G, Taubert J, Nadig A. Editorial: Improving the quality of life of autistic people and their caregivers from diverse backgrounds: methods and approaches. Frontiers in psychology. 2023; 14: 1242236.

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30. Kewalramani S, Allen KA, Leif E, Ng A. A Scoping Review of the Use of Robotics Technologies for Supporting Social-Emotional Learning in Children with Autism. Journal of autism and developmental disorders. 2023.

This scoping review synthesises the current research into robotics technologies for promoting social-emotional learning in children with autism spectrum disorder. It examines the types of robotics technologies employed, their applications, and the gaps in the existing literature. Our scoping review adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines. The systematic search of relevant databases allowed us to identify studies that use robotics technologies for fostering social, emotional, and cognitive skills in young children with autism. Our review has revealed that various robots, such as Nao, Kaspar, and Zeno, have been used to support the development of social and emotional skills through imitation games, turn-taking, joint attention, emotional recognition, and conversation. As most of these studies were conducted in clinical settings, there is a need for further research in classroom and community-based environments. Additionally, the literature calls for more high-quality longitudinal studies to assess the long-term effectiveness and sustainability of robot-assisted therapy and to assess adaptive and personalised interventions tailored to individual needs. More emphasis is recommended on professional development for educators, parents, and health professionals to incorporate robotics technologies as evidence-based interventions as a pathway for creating inclusive learning environments for children with autism.

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31. Kuruppath P, Xue L, Pouille F, Jones ST, Schoppa NE. Hyperexcitability in the Olfactory Bulb and Impaired Fine Odor Discrimination in the Fmr1 KO Mouse Model of Fragile X Syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2023; 43(48): 8243-58.

Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders (ASDs) in humans. FXS is caused by loss of expression of the fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here, we conducted experiments in wild-type (WT) and Fmr1 knock-out (KO; Fmr1(-/y) ) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) in Fmr1 KO mice displayed greatly enhanced excitation under baseline conditions, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of spontaneous LLDs (sLLDs), which appeared to be because of a decrease in GABAergic synaptic inhibition in glomeruli leading to more feedforward excitation, caused a reduction in the reliability of stimulation-evoked responses in MCs. In addition, in a go/no-go operant discrimination paradigm, we found that Fmr1 KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the Fmr1 KO-induced reduction in MC response reliability is one plausible mechanism for the impaired fine odor discrimination.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-used Fmr1 knock-out (KO) mouse model of FXS. Our studies indicate that Fmr1 KO alters the local excitation/inhibition balance in the bulb, similar to what Fmr1 KO does in other brain circuits, but through a novel mechanism that involves enhanced feedforward excitation. Furthermore, Fmr1 KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by changes in neural response reliability.

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32. Li Q, Li W, Hu K, Wang Y, Li Y, Xu J. A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway. Clinical genetics. 2023.

Autism spectrum disorder (ASD) is a highly variable neurodevelopmental disorder that typically manifests childhood, characterized by a triad of symptoms: impaired social interaction, communication difficulties, and restricted interests with repetitive behaviors. De novo variants in related genes can cause ASD. We present the case of a 6-year-old Chinese boy with autistic behavior, including language communication impairments, intellectual disabilities, stunted development, and irritability in social interactions. Using Sanger sequencing, we confirmed a pathogenic in the RERE gene (NM_012102.4) (c.3732delC, p.Tyr1245Thrfs*12; EX21; Het). Subsequently, we generated an RERE point mutation cell line (ReMut) using CRISPR/Cas9 Targeted Genome Editing. Immunofluorescence was conducted to determine the location of the mutant RERE. RNA-sequencing and mass spectrometry analyses were performed to elucidate the ASD-related genes and signaling pathways disrupted by this variant in RERE. We identified 3790 differentially expressed genes and 684 differentially expressed proteins. The SHH signaling pathway was found to be downregulated, and the Hippo pathway was upregulated in ReMut. Genes implicated in autism, such as CNTNAP2, STX1A, FARP2, and GPC1, were significantly downregulated. Simultaneously, we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient. In conclusion, we report a de novo variant in RERE associated with autistic behavior. The finding that ASD is associated with RERE variants underscore the role of genetic factors in ASD and provides insights regarding the mechanisms underlying RERE variants in disease onset.

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33. Liang Y, Zhong L, Lu J, Yao P. Editorial: Endocrinological factors for autism: prenatal biomarkers, early diagnosis and symptom treatment. Frontiers in endocrinology. 2023; 14: 1298381.

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34. López-Tobón A, Shyti R, Villa CE, Cheroni C, Fuentes-Bravo P, Trattaro S, Caporale N, Troglio F, Tenderini E, Mihailovich M, Skaros A, Gibson WT, Cuomo A, Bonaldi T, Mercurio C, Varasi M, Osborne L, Testa G. GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders. Science advances. 2023; 9(48): eadh2726.

Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome featuring hypersociability, while duplication causes 7q11.23 microduplication syndrome (7Dup), frequently exhibiting autism spectrum disorder (ASD). Converging evidence indicates GTF2I as key mediator of the cognitive-behavioral phenotypes, yet its role in cortical development and behavioral hallmarks remains largely unknown. We integrated proteomic and transcriptomic profiling of patient-derived cortical organoids, including longitudinally at single-cell resolution, to dissect 7q11.23 dosage-dependent and GTF2I-specific disease mechanisms. We observed dosage-dependent impaired dynamics of neural progenitor proliferation, transcriptional imbalances, and highly specific alterations in neuronal output, leading to precocious excitatory neuron production in 7Dup, which was rescued by restoring physiological GTF2I levels. Transgenic mice with Gtf2i duplication recapitulated progenitor proliferation and neuronal differentiation defects alongside ASD-like behaviors. Consistently, inhibition of lysine demethylase 1 (LSD1), a GTF2I effector, was sufficient to rescue ASD-like phenotypes in transgenic mice, establishing GTF2I-LSD1 axis as a molecular pathway amenable to therapeutic intervention in ASD.

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35. Maggio R, Turriziani L, Campestre C, Di Cara M, Tripodi E, Impallomeni C, Quartarone A, Passantino C, Cucinotta F. An individual-supported program to enhance placement in a sheltered work environment of autistic individuals mostly with intellectual disability: a prospective observational case series in an Italian community service. Frontiers in psychiatry. 2023; 14: 1225236.

INTRODUCTION: Autism spectrum disorder is a lifelong neurodevelopmental disorder. The profile of functioning in autistic people is very heterogeneous, and it is necessary to take into account individual characteristics to better support integration in the workplace. However, unemployment rates are higher for autistic people than for other types of disabilities. We present a prospective case series to explore the feasibility and efficacy of an individual-supported program to enhance placement in a sheltered work environment delivered by an Italian community day care center. METHODS: Autistic subjects, aged from 12 to 31 years, participated in an individual-supported program regarding employment in sheltered art workshops, integrated into the regular activity of a semi-residential center three times a week for 1 year. Their feasibility retention rate and time worked per session were registered; moreover, working methods efficacy and self-organization improvement were tracked by the Likert-based rating system. Secondary outcome measures span functional levels, challenge behaviors, and sensory problems. RESULTS: All the individuals presented a good adaptation to the environment, with a significant increase in time worked per session. After 1 year, the intervention allowed an increase in tasks completed in an assigned complex job and an improvement in self-organization within the work schedule in a group of subjects consisting mainly of severe-to-moderate levels of autism severity (86.6%). Finally, we observed a significant increase in independent functioning areas of the TEACCH transitional assessment profile. Challenge behaviors and sensory problems were also recorded. CONCLUSION: This case series supports the idea that individual-supported programs for placement in sheltered job environments delivered by community day care centers could be feasible and effective for ASD with higher levels of severity and co-occurring intellectual disability. Further targeted studies based on community models and accessible methods need to be planned to define the effectiveness of the intervention and promote improved practice at the community level with a better social impact.

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36. Milner V, Colvert E, Hull L, Cook J, Ali D, Mandy W, Happé F. Does camouflaging predict age at autism diagnosis? A comparison of autistic men and women. Autism research : official journal of the International Society for Autism Research. 2023.

It is frequently reported that females are likely to receive an autism diagnosis at a later age than their male counterparts, despite similar levels of autistic traits. It has been suggested that this delay in diagnosis may in part reflect the propensity of females, more than males, to engage in camouflaging behaviors that reduce the appearance of autism-related traits. This article presents two studies which examined the relationship between gender/sex, camouflaging, and age at diagnosis in two samples of (cis-gender) autistic adults. Study 1 included data from three online samples including 242 autistic men and 570 autistic women aged 18-75 years. Study 2 included data from a longitudinal population-based sample including 24 autistic men and 35 autistic women aged 20-24 years. Camouflaging was measured with the self-report Camouflaging Autistic Traits Questionnaire (CAT-Q). Overall, the results showed that, on average, females were diagnosed later than males. There was a stronger relationship between camouflaging and age at autism diagnosis (AaD) for females, compared with males. Within sample one, there was a significant camouflaging-by-sex interaction; high-camouflaging females had a later AaD. The role of autistic traits and changes in attitudes towards female autism and camouflaging need further exploration. These findings highlight the need for greater clinician and key stakeholder awareness and understanding of camouflaging behavior, particularly for females, during the diagnostic process.

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37. Mohamed DI, Abo Nahas HH, Elshaer AM, El-Waseef D, El-Kharashi OA, Mohamed SMY, Sabry YG, Almaimani RA, Almasmoum HA, Altamimi AS, Ibrahim IAA, Alshawwa SZ, Jaremko M, Emwas AH, Saied EM. Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies. Frontiers in cellular neuroscience. 2023; 17: 1268126.

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.

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38. Muharib R, Walker V, Dunn W. Effects of Interventions Involving Tablet-Based Speech-Generating Devices for Individuals with ASD: A Meta-analysis. Journal of autism and developmental disorders. 2023.

The purpose of this review was to assess the effectiveness of tablet-based speech-generating devices (SGDs) in improving communication skills for individuals with autism spectrum disorder (ASD). A total of 31 single-case design intervention studies involving 84 individuals with ASD were reviewed and included in the analysis. We calculated Tau-U to evaluate the impact of interventions involving tablet-based SGDs on four different communication responses: specifically, mands, intraverbals, tacts, and vocalizations. To explore potential moderating variables for mand outcomes, we used the Kruskal-Wallis one-way test. The analysis revealed that interventions utilizing tablet-based SGDs led to improvements in communication responses. Specifically, large to very large changes were observed in mand and intraverbal responses, whereas moderate changes were noted in tact responses and vocalizations. The findings of this review underscore the potential of tablet-based SGDs in enhancing communication among individuals with ASD. We discuss the findings and provide implications for future research and practice.

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39. Newman BT, Jacokes Z, Venkadesh S, Webb SJ, Kleinhans NM, McPartland JC, Druzgal TJ, Pelphrey KA, Van Horn JD. Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder. bioRxiv : the preprint server for biology. 2023.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a novel metric termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1/T2 ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel neuroimaging metric, aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

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40. Odabasi YC, Yanasik S, Saglam-Metiner P, Kaymaz Y, Yesil-Celiktas O. Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways. ACS omega. 2023; 8(46): 44148-62.

Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder that has no cure apart from symptomatic treatments. While intense research efforts are required to fulfill this unmet need, the fundamental challenge is to obtain sufficient patient data. In this study, we used human transcriptomic data of four different sample types from RTT patients including induced pluripotent stem cells, differentiated neural progenitor cells, differentiated neurons, and postmortem brain tissues with an increasing in vivo-like complexity to unveil specific trends in gene expressions across the samples. Based on DEG analysis, we identified F8A3, CNTN6, RPE65, and COL19A1 to have differential expression levels in three sample types and also observed previously reported genes such as MECP2, FOXG1, CACNA1G, SATB2, GABBR2, MEF2C, KCNJ10, and CUX2 in our study. Considering the significantly enriched pathways for each sample type, we observed a consistent increase in numbers from iPSCs to NEUs where MECP2 displayed profound effects. We also validated our GSEA results by using single-cell RNA-seq data. In WGCNA, we elicited a connection among MECP2, TNRC6A, and HOXA5. Our findings highlight the utility of transcriptomic analyses to determine genes that might lead to therapeutic strategies.

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41. Panerai S, Catania V, Ingoglia S, Ruccella D, Ferri R, Zingale M, Fasciana D, Elia M. Eating and Sensory Features of Children With Autism Spectrum Disorder and Their Typically Developing Peers. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 2023; 77(6).

IMPORTANCE: Impaired sensory processing is associated with eating problems. There seem to be no previous studies that compare those who have autism spectrum disorder (ASD) with eating problems (ASD-W) and those with ASD without eating problems (ASD-WO) with typically developing (TD) groups. Comparisons are expected to provide further knowledge to guide the intervention programs. OBJECTIVE: To investigate differences among ASD-W, ASD-WO, and TD groups in eating and sensory features; to detect associations between sensory and eating behaviors and any most involved sensory dimensions; and to search for age-related differences in sensory and eating features in ASD. DESIGN: Nonrandomized comparison study. SETTING: Questionnaires administered as parent interviews. PARTICIPANTS: A total of 165 children were recruited: 117 with ASD and 48 TD children. OUTCOMES AND MEASURES: Standardized questionnaires: the Brief Autism Mealtime Behaviors Inventory for eating problems; the Short Sensory Profile and the Sensory Experience Questionnaire for sensory problems. RESULTS: The ASD-W group showed generalized, impaired eating behaviors and turned out to be the most impaired with regard to sensory responsiveness. No differences in feeding behaviors were found between the ASD-WO and TD groups. All children with ASD showed sensory hyper- or hyporesponsiveness. Four main sensory dimensions were found to be associated with eating behaviors in ASD. No age differences were found in the eating and sensory behaviors of children with ASD. CONCLUSIONS AND RELEVANCE: Differing eating and sensory profiles were found between the ASD and TD groups, especially in children with ASD-W. Early eating interventions using sensory stimulations are strongly recommended. What This Article Adds: This study reports novel information derived from the comparisons of children with ASD with eating problems and those with ASD without eating problems with typically developing groups of children.

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42. Parrella NF, Hill AT, Dipnall LM, Loke YJ, Enticott PG, Ford TC. Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review. Journal of psychiatric research. 2023; 169: 113-25.

The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) has a prominent role in regulating neural development and function, with disruption to GABAergic signalling linked to behavioural phenotypes associated with neurodevelopmental disorders, particularly autism. Such neurochemical disruption, likely resulting from diverse genetic and molecular mechanisms, particularly during early development, can subsequently affect the cellular balance of excitation and inhibition in neuronal circuits, which may account for the social processing difficulties observed in autism and related conditions. This comprehensive narrative review integrates diverse streams of research from several disciplines, including molecular neurobiology, genetics, epigenetics, and systems neuroscience. In so doing it aims to elucidate the relevance of inhibitory dysfunction to autism, with specific focus on social processing difficulties that represent a core feature of this disorder. Many of the social processing difficulties experienced in autism have been linked to higher levels of the excitatory neurotransmitter glutamate and/or lower levels of inhibitory GABA. While current therapeutic options for social difficulties in autism are largely limited to behavioural interventions, this review highlights the psychopharmacological studies that explore the utility of GABA modulation in alleviating such difficulties.

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43. Plank IS, Koehler JC, Nelson AM, Koutsouleris N, Falter-Wagner CM. Automated extraction of speech and turn-taking parameters in autism allows for diagnostic classification using a multivariable prediction model. Frontiers in psychiatry. 2023; 14: 1257569.

Autism spectrum disorder (ASD) is diagnosed on the basis of speech and communication differences, amongst other symptoms. Since conversations are essential for building connections with others, it is important to understand the exact nature of differences between autistic and non-autistic verbal behaviour and evaluate the potential of these differences for diagnostics. In this study, we recorded dyadic conversations and used automated extraction of speech and interactional turn-taking features of 54 non-autistic and 26 autistic participants. The extracted speech and turn-taking parameters showed high potential as a diagnostic marker. A linear support vector machine was able to predict the dyad type with 76.2% balanced accuracy (sensitivity: 73.8%, specificity: 78.6%), suggesting that digitally assisted diagnostics could significantly enhance the current clinical diagnostic process due to their objectivity and scalability. In group comparisons on the individual and dyadic level, we found that autistic interaction partners talked slower and in a more monotonous manner than non-autistic interaction partners and that mixed dyads consisting of an autistic and a non-autistic participant had increased periods of silence, and the intensity, i.e. loudness, of their speech was more synchronous.

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44. Potabattula R, Prell A, Dittrich M, Nava C, Depienne C, Bejaoui Y, El Hajj N, Hahn T, Schorsch M, Haaf T. Effects of paternal and chronological age on BEGAIN methylation and its possible role in autism. Aging. 2023; 15(22): 12763-79.

Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal age effects on the sperm epigenome. The brain enriched guanylate kinase associated (BEGAIN) protein is involved in protein-protein interactions at and transmission across synapses. Since several epigenome-wide methylation screens reported a paternal age effect on sperm BEGAIN methylation, here we confirmed a significant negative correlation between BEGAIN promoter methylation and paternal age, using more sensitive bisulfite pyrosequencing and a larger number of sperm samples. Paternal age-associated BEGAIN hypomethylation was also observed in fetal cord blood (FCB) of male but not of female offspring. There was no comparable maternal age effect on FCB methylation. In addition, we found a significant negative correlation between BEGAIN methylation and chronological age (ranging from 1 to 70 years) in peripheral blood samples of male but not of female donors. BEGAIN hypomethylation was more pronounced in male children, adolescents and adults suffering from ASD compared to controls. Both genetic variation (CC genotype of SNP rs7141087) and epigenetic factors may contribute to BEGAIN promoter hypomethylation. The age- and sex-specific BEGAIN methylation trajectories in the male germ line and somatic tissues, in particular the brain, support a role of this gene in ASD development.

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45. Rahmatullah N, Schmitt LM, De Stefano L, Post S, Robledo J, Chaudhari G, Pedapati E, Erickson C, Portera-Cailliau C, Goel A. Hypersensitivity to Distractors in Fragile X Syndrome from Loss of Modulation of Cortical VIP Interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2023; 43(48): 8172-88.

Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from Fmr1 (-/-) mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS.SIGNIFICANCE STATEMENT Sensory hypersensitivity, impulsivity, and persistent inattention are among the most consistent clinical features of FXS, all of which impede daily functioning and create barriers to learning. However, the neural mechanisms underlying sensory over-reactivity remain elusive. To overcome a significant challenge in translational FXS research we demonstrate a compelling alignment of sensory over-reactivity in both humans with FXS and Fmr1 (-/-) mice (the principal animal model of FXS) using a novel analogous distractor task. Two-photon microscopy in mice revealed that lack of modulation by VIP cells contributes to susceptibility to distractors. Implementing research efforts we describe here can help identify dysfunctional neural mechanisms associated not only with sensory issues but broader impairments, including those in learning and cognition.

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46. Ranieri A, Mennitti C, Falcone N, La Monica I, Di Iorio MR, Tripodi L, Gentile A, Vitale M, Pero R, Pastore L, D’Argenio V, Scudiero O, Lombardo B. Positive effects of physical activity in autism spectrum disorder: how influences behavior, metabolic disorder and gut microbiota. Frontiers in psychiatry. 2023; 14: 1238797.

Autism spectrum disorder is a neurodevelopmental disorder characterized by social interactions and communication skills impairments that include intellectual disabilities, communication delays and self-injurious behaviors; often are present systemic comorbidities such as gastrointestinal disorders, obesity and cardiovascular disease. Moreover, in recent years has emerged a link between alterations in the intestinal microbiota and neurobehavioral symptoms in children with autism spectrum disorder. Recently, physical activity and exercise interventions are known to be beneficial for improving communication and social interaction and the composition of microbiota. In our review we intend to highlight how different types of sports can help to improve communication and social behaviors in children with autism and also show positive effects on gut microbiota composition.

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47. Robinson BG, Oster BA, Robertson K, Kaltschmidt JA. Loss of ASD-related molecule Cntnap2 affects colonic motility in mice. Frontiers in neuroscience. 2023; 17: 1287057.

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2’s expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in vivo and ex vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.

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48. Sese LVC, Guillermo MCL. A Story of Hope: How a Community Project is Transforming the Lives of Filipino Children With Intellectual and Developmental Disabilities. Global pediatric health. 2023; 10: 2333794×231211215.

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49. Singh A, Balasundaram MK, Gupta D. Trofinetide in Rett syndrome: A brief review of safety and efficacy. Intractable & rare diseases research. 2023; 12(4): 262-6.

Rett syndrome (RTT) is a rare genetic neurological disorder that primarily affects girls and is caused by mainly mutations in the methyl-CpG-binding protein 2 (MECP2) gene, leading to critical issues in normal brain function. The condition has a global prevalence of 5 to 10 cases per 100,000 females, and there is currently no cure for RTT. However, therapy is available to manage the symptoms and improve quality of life. Trofinetide, an insulin-like growth factor 1, was originally developed as a stroke medication and progressed to Phase II clinical trials, where it exhibited favorable safety and efficacy profiles by improving several core RTT symptoms. Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder. It has also shown to be safe, well-tolerated and with no known drug interactions. These findings suggest that Trofinetide is a promising treatment option for individuals with RTT.

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50. Smith J, Rabba AS, Datta P, Dresens E, Wang R, Cong L, Dang N, Hall G, Heyworth M, Lawson W, Lee P, Lilley R, Ma E, Nguyen HTT, Nguyen KV, Nguyen P, Yeow CT, Pellicano E. ‘It’s really important to be collaborating’: Experiences of participatory research for Chinese and Vietnamese parents of autistic children. Autism & developmental language impairments. 2023; 8: 23969415231210482.

BACKGROUND AND AIMS: Participatory research involves academic partners working together with the community that is affected by research to make decisions about that research. Such approaches often result in research that is more respectful of, and responsive to, community preferences – and is vital in the context of autism research with culturally and linguistically diverse (CALD) communities. Whilst participatory approaches are becoming more commonplace within CALD autism research, no studies have explored the experiences of being involved in autism research from the perspectives of CALD community partners over the course of a study. This paper intended to address this gap by reporting on the experiences of CALD parents of autistic children who were community partners in a 1-year Australian research project exploring home-school partnerships for CALD parents of autistic children. We aimed to: (1) report on how parents’ involvement in the research process shaped the home-school partnerships study over time and (2) understand their experiences of being community partners on the home-school partnerships project. METHODS: Using key principles of participatory approaches, we established Chinese and Vietnamese parent advisory groups to contribute to a project exploring home-school partnerships for parents of autistic children from CALD backgrounds in Australia. Advisory groups included parents of autistic children from Chinese/Vietnamese backgrounds, as well as interpreters, professionals and researchers. We documented how parents’ participation as community partners shaped the home-school partnerships study over the course of the project. We also elicited parents’ own views and experiences of being community partners through informal, open-ended questions at the beginning and end of the study. RESULTS: We found that parents’ input fundamentally shaped the broader home-school partnership study, from meaningful, accurate translation of interview schedules through to making decisions regarding community-specific recommendations and dissemination plans. Parents themselves reported being keen to collaborate and to hear and share opinions for the purpose of the home-school partnership study – although they noted how emotionally difficult sharing their stories could be. While they initially had some concerns about combining being involved as a community partner with their existing responsibilities, ultimately, parents were surprised by the scope of the home-school partnership study and their level of involvement as community partners. Through hearing others’ stories and sharing their own in advisory group meetings, parents reported ancillary benefits of their involvement, including increased self-advocacy and well-being. CONCLUSIONS: These findings show how research that is conducted in partnership with diverse members of the autism community has the capacity to improve the quality of the research and benefit community partners. IMPLICATIONS: This study clearly documents the benefits and potential challenges of participatory approaches with CALD communities. These findings emphasise to researchers and funders the importance of including extra time and money within budgets in order to produce meaningful research that is respectful and responsive to communities.

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51. Smith MJ, Sherwood KL, Genova HM, Ross B, DaWalt LS, Bishop L, Telfer D, Brown C, Sanchez B, Kallen MA. Psychometric properties of the mock interview rating scale for autistic transition-age youth. Frontiers in psychiatry. 2023; 14: 1235056.

BACKGROUND: Employment is a major contributor to quality of life. However, autistic people are often unemployed and underemployed. One potential barrier to employment is the job interview. However, the availability of psychometrically-evaluated assessments of job interviewing skills is limited for autism services providers and researchers. OBJECTIVE: We analyzed the psychometric properties of the Mock Interview Rating Scale that was adapted for research with autistic transition-age youth (A-MIRS; a comprehensive assessment of video-recorded job interview role-play scenarios using anchor-based ratings for 14 scripted job scenarios). METHODS: Eighty-five transition-age youth with autism completed one of two randomized controlled trials to test the effectiveness of two interventions focused on job interview skills. All participants completed a single job interview role-play at pre-test that was scored by raters using the A-MIRS. We analyzed the structure of the A-MIRS using classical test theory, which involved conducting both exploratory and confirmatory factor analyzes, Rasch model analysis and calibration techniques. We then assessed internal consistency, inter-rater reliability, and test-retest reliability. Pearson correlations were used to assess the A-MIRS’ construct, convergent, divergent, criterion, and predictive validities by comparing it to demographic, clinical, cognitive, work history measures, and employment outcomes. RESULTS: Results revealed an 11-item unidimensional construct with strong internal consistency, inter-rater reliability, and test-retest reliability. Construct [pragmatic social skills (r = 0.61, p < 0.001), self-reported interview skills (r = 0.34, p = 0.001)], divergent [e.g., age (r = -0.13, p = 0.26), race (r = 0.02, p = 0.87)], and predictive validities [competitive employment (r = 0.31, p = 0.03)] received initial support via study correlations, while convergent [e.g., intrinsic motivation (r = 0.32, p = 0.007), job interview anxiety (r = -0.19, p = 0.08)] and criterion [e.g., prior employment (r = 0.22, p = 0.046), current employment (r = 0.21, p = 0.054)] validities were limited. CONCLUSION: The psychometric properties of the 11-item A-MIRS ranged from strong-to-acceptable, indicating it may have utility as a reliable and valid method for assessing the job interview skills of autistic transition-age youth.

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52. Tang T, Li C, Zhang S, Chen Z, Yang L, Mu Y, Chen J, Xu P, Gao D, Li F, He B, Zhu Y. A Hybrid Graph Network Model for ASD Diagnosis Based on Resting-state EEG Signals. Brain research bulletin. 2023: 110826.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder and early diagnosis is crucial for effective treatment. Stable and effective biomarkers are essential for understanding the underlying causes of the disorder and improving diagnostic accuracy. Electroencephalography (EEG) signals have proven to be reliable biomarkers for diagnosing ASD. Extracting stable connectivity patterns from EEG signals helps ensure robustness in ASD diagnostic systems. In this study, we propose a hybrid graph convolutional network framework called Rest-HGCN, which utilizes resting-state EEG signals to capture differential patterns of brain connectivity between normal children and ASD patients using graph learning strategies. The Rest-HGCN combines brain network analysis techniques and data-driven strategies to extract discriminative graph features from resting-state EEG signals. By automatically extracting differential graph patterns from these signals, the Rest-HGCN achieves reliable ASD diagnosis. To evaluate the performance of Rest-HGCN, we conducted ASD diagnosis experiments using k-fold cross-validation on the public ABC-CT resting EEG dataset. The proposed Rest-HGCN model achieved accuracies of 87.12% and 85.32% in single-subject and cross-experiment analyses, respectively. The results suggest that Rest-HGCN can effectively capture discriminant graph patterns from resting EEG signals and achieve robust ASD diagnosis. This may provide an effective and convenient tool for clinical ASD diagnosis.

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53. Taylor BJ, Pedersen KA, Mazefsky CA, Lamy MA, Reynolds CF, 3rd, Strathmann WR, Siegel M. From Alert Child to Sleepy Adolescent: Age Trends in Chronotype, Social Jetlag, and Sleep Problems in Youth with Autism. Journal of autism and developmental disorders. 2023.

PURPOSE: Developmental changes in sleep in youth with autism spectrum disorder (ASD) are understudied. In non-ASD youth, adolescents exhibit a « night owl chronotype » (i.e., later sleep/wake timing) and social jetlag (i.e., shifts in sleep timing across school nights and weekends), with corresponding sleep problems. The purpose of this study is to evaluate age trends in chronotype, social jetlag, and sleep problems in high-risk youth with ASD. METHODS: Youth with ASD (N = 171), ages 5-21 years old, were enrolled at the time of admission to specialized psychiatric units. Caregivers reported children’s demographic information, habitual sleep timing, and sleep problems. Multivariate analyses evaluated the effect of age on chronotype, social jetlag, and sleep problems and the effects of chronotype and social jetlag on sleep problems. Covariates and moderators included sex, race, verbal ability, autism symptom severity, supplemental melatonin, and pubertal status. RESULTS: Older age was associated with later chronotype, more social jetlag, fewer sleep anxiety/co-sleeping problems, fewer night waking and parasomnia problems, and more daytime alertness problems. The effect of age on chronotype was stronger for youth with greater social affective symptom severity. Mediation analyses showed that later chronotype statistically mediated the association between age and daytime alertness problems. CONCLUSIONS: Youth with ASD may exhibit night owl chronotype behavior and social jetlag as they enter adolescence. Shifts toward a later chronotype may be exacerbated by autism severity and may contribute to alertness problems and sleepiness during the day. Chronotype is modifiable and may be leveraged to improve daytime functioning in youth with ASD.

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54. Zain E, Fukui N, Watanabe Y, Hashijiri K, Motegi T, Ogawa M, Egawa J, Nishijima K, Someya T. The three-factor structure of the Autism-Spectrum Quotient Japanese version in pregnant women. Frontiers in psychiatry. 2023; 14: 1275043.

BACKGROUND: There is a rising interest in perinatal mental health studies, and proper psychometric tools to assess autistic traits among this population in Japan are vital. OBJECTIVE: This study aimed to clarify the optimal factor structure of the AQ as part of a perinatal mental health research project. METHODS: We used the Japanese version of the AQ (AQ-J) to measure autistic-like traits in pregnant women. Participants were 4,287 Japanese women who were pregnant or who had given birth within the last month. We performed exploratory factor analysis (EFA) using the first sample group (n = 2,154) to obtain factor structures for the final item selections. We performed confirmatory factor analysis (CFA) using the second sample group (n = 2,133) to obtain a model with good fit, then compared the model to all previously proposed models to determine the best-fitting model. RESULTS: The EFA analysis identified a model consisting of 25 items distributed across three factors. Cronbach’s alpha for the total 25-item AQ-J, 9-item « Social interaction » factor, 11-item « Non-verbal communication » factor, and 5-item « Restricted interest » factor was 0.829, 0.829, 0.755, and 0.576, respectively. McDonald’s omega and its 95% confidence interval were 0.826 (0.821-0.836), 0.835 (0.821-0.837), 0.755 (0.744-0.766), and 0.603 (0.556-0.596), respectively. CFA confirmed that the three-factor structure had an acceptable fit (goodness of fit index: 0.900, comparative fit index: 0.860, root mean square error of approximation: 0.066). These findings indicated that the three-factor model was better than the 13 existing models. CONCLUSION: The findings are discussed in relation to the adequacy of the AQ-J for assessing autistic traits in perinatal women. We recommend the use of this 25-item, three-factor AQ-J model for this population owing to its superiority to all previous models.

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