1. Arutiunian V, Arcara G, Buyanova I, Davydova E, Pereverzeva D, Sorokin A, Tyushkevich S, Mamokhina U, Danilina K, Dragoy O. Neuromagnetic 40 Hz Auditory Steady-State Response in the left auditory cortex is related to language comprehension in children with Autism Spectrum Disorder. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 122: 110690.

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD), but its neural mechanisms are still poorly understood. Some studies hypothesize that the atypical low-level sensory perception in the auditory cortex accounts for the abnormal language development in these children. One of the potential non-invasive measures of such low-level perception can be the cortical gamma-band oscillations registered with magnetoencephalography (MEG), and 40 Hz Auditory Steady-State Response (40 Hz ASSR) is a reliable paradigm for eliciting auditory gamma response. Although there is research in children with and without ASD using 40 Hz ASSR, nothing is known about the relationship between this auditory response in children with ASD and their language abilities measured directly in formal assessment. In the present study, we used MEG and individual brain models to investigate 40 Hz ASSR in primary-school-aged children with and without ASD. It was also used to assess how the strength of the auditory response is related to language abilities of children with ASD, their non-verbal IQ, and social functioning. A total of 40 children were included in the study. The results demonstrated that 40 Hz ASSR was reduced in the right auditory cortex in children with ASD when comparing them to typically developing controls. Importantly, our study provides the first evidence of the association between 40 Hz ASSR in the language-dominant left auditory cortex and language comprehension in children with ASD. This link was domain-specific because the other brain-behavior correlations were non-significant.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bar Yehuda S, Bauminger-Zviely N. Social-Motor Coordination Between Peers: Joint Action Developmental Trajectories in ASD and TD. Journal of autism and developmental disorders. 2022.

Coordinating a physical movement in time and space with social and nonsocial partners to achieve a shared goal – « joint action » (JA) – characterizes many peer-engagement situations that pose challenges for individuals with autism spectrum disorder (ASD). This cross-sectional study examined development of JA capabilities comparing ASD versus typically developing (TD) groups in early childhood, preadolescence, and adolescence while performing mirroring and complementing JA tasks with social (peer) and nonsocial (computer) partners. Results indicated better motor coordination abilities on computerized tasks than in peer dyads, with larger peer-dyad deficits shown by the ASD group. Developmental growth in JA abilities emerged, but the ASD group lagged behind same-age peers with TD. Socio-motor interventions may offer new channels to facilitate peer engagement in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

3. Buzzelli V, Carbone E, Manduca A, Schiavi S, Feo A, Perederiy JV, Ambert KH, Hausman M, Trezza V. Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome. Psychopharmacology. 2022.

RATIONALE: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neurodevelopmental disorders, manifesting as behavioral and emotional symptoms. Thus, compounds that stimulate serotonergic signaling such as psilocybin may offer promise as effective early interventions for developmental disorders such as ASD and FXS. OBJECTIVES: The aim of the present study was to test whether different protocols of psilocybin administration mitigate cognitive deficits displayed by the recently validated Fmr1-(Δ)exon 8 rat model of ASD, which is also a model of FXS. RESULTS: Our results revealed that systemic and oral administration of psilocybin microdoses normalizes the aberrant cognitive performance displayed by adolescent Fmr1-(Δ)exon 8 rats in the short-term version of the novel object recognition test-a measure of exploratory behavior, perception, and recognition. CONCLUSIONS: These data support the hypothesis that serotonin-modulating drugs such as psilocybin may be useful to ameliorate ASD-related cognitive deficits. Overall, this study provides evidence of the beneficial effects of different schedules of psilocybin treatment in mitigating the short-term cognitive deficit observed in a rat model of FXS.

Lien vers le texte intégral (Open Access ou abonnement)

4. Cesana M, Vaccaro L, Larsen MJ, Kibæk M, Micale L, Riccardo S, Annunziata P, Colantuono C, Di Filippo L, De Brasi D, Castori M, Fagerberg C, Acquaviva F, Cacchiarelli D. Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association. Human genetics. 2022.

The application of next-generation sequencing (NGS) to clinical practice is still hampered by the ability to interpret the clinical relevance of novel variants and the difficulty of evaluating their effect in specific tissues. Here, we applied integrated genomic approaches for interrogating blood samples of two unrelated individuals with neurodevelopmental disorders and identified a novel neuro-pathogenic role for the Mitogen-Activated Protein Kinase 4 gene (MAP4K4). In particular, we identified two novel frameshift variants in coding exons expressed in the blood and neuronal isoforms. Both variants were predicted to generate non-sense-mediated decay. By transcriptome analysis, we simultaneously demonstrated the deleterious effect of the identified variants on the splicing activity and stability of MAP4K4 mRNA. Therefore, we propose MAP4K4 as a novel causative gene for non-syndromic and syndromic neurodevelopmental disorders. Altogether, we prove the efficacy of an integrated approach of exome and transcriptome sequencing in the resolution of undiagnosed cases by leveraging the analysis of variants in genes expressed in peripheral blood.

Lien vers le texte intégral (Open Access ou abonnement)

5. Derguy C, Aubé B, Rohmer O, Loyal D. Evaluation of teachers’ knowledge and attitudes regarding the school inclusion of autistic children: Validation of a brief assessment toolkit. The British journal of educational psychology. 2022.

BACKGROUND: Teachers’ level of knowledge regarding autism and their attitudes towards inclusion are major levers for the successful schooling of autistic students. However, there are currently insufficient validated tools for evaluating these two concepts among teachers that are adapted to the French context and to the constraints of the classroom setting. AIMS: This study was designed to test both the validity of The Autism Knowledge Screening Scale (AKSS) and of the Autism Attitude Scale for Teachers (AAST) among French teachers. SAMPLE: Our final sample consisted of 307 French teachers (50.5% primary school teachers and 49.5% secondary school teachers). METHODS: First, confirmatory factor analyses were conducted to test the two initial factor structures and an exploratory factor analysis was conducted regarding the AKSS. Second, criterion validity was assessed for each of the two scales. RESULTS: Concerning knowledge of autism, a two-factor model (8 items) explaining 53% of the variance was observed. The first factor represented knowledge about aetiology and the second represented knowledge about symptoms. Concerning attitudes towards autism, a one-factor model (14 items) exhibited good model fit (χ (2) /df = 1.71, RMSEA = .048, AGFI = .979, SRMR = .068, CFI = .987, NNFI = .984). As expected, participants who were specialized teachers, had training, and a high degree of contact with autism had more knowledge (regarding aetiology but not regarding symptoms) and more positive attitudes. CONCLUSIONS: This study validated two quick-to-use tools for making an initial diagnosis of teachers’ knowledge and attitudes regarding the school inclusion of autistic children. The use of these tools could help to fine-tune the content of training programs for teachers and test their efficacy, particularly in France where the inclusion of autistic children is still far from international standards.

Lien vers le texte intégral (Open Access ou abonnement)

6. Kim Y, Jeon SJ, Gonzales EL, Shin D, Remonde CG, Ahn T, Shin CY. Pirenperone relieves the symptoms of fragile X syndrome in Fmr1 knockout mice. Scientific reports. 2022; 12(1): 20966.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by the loss of Fragile X-linked mental retardation protein (FMRP), an RNA binding protein that can bind and recognize different RNA structures and regulate the target mRNAs’ translation involved in neuronal synaptic plasticity. Perturbations of this gene expression network have been related to abnormal behavioral symptoms such as hyperactivity, and impulsivity. Considering the roles of FMRP in the modulation of mRNA translation, we investigated the differentially expressed genes which might be targeted to revert to normal and ameliorate behavioral symptoms. Gene expression data was analyzed and used the connectivity map (CMap) to understand the changes in gene expression in FXS and predict the effective drug candidates. We analyzed the GSE7329 dataset that had 15 control and 8 FXS patients’ lymphoblastoid samples. Among 924 genes, 42 genes were selected as signatures for CMap analysis, and 24 associated drugs were found. Pirenperone was selected as a potential drug candidate for FXS for its possible antipsychotic effect. Treatment of pirenperone increased the expression level of Fmr1 gene. Moreover, pirenperone rescued the behavioral deficits in Fmr1 KO mice including hyperactivity, spatial memory, and impulsivity. These results suggest that pirenperone is a new drug candidate for FXS, which should be verified in future studies.

Lien vers le texte intégral (Open Access ou abonnement)

7. Lee HK, Jin J. The effect of a virtual reality exergame on motor skills and physical activity levels of children with a developmental disability. Research in developmental disabilities. 2023; 132: 104386.

BACKGROUND: It is well documented that regular physical activity (PA) participation improves physical functions of children with a developmental disability (DD). Researchers have begun to pay attention to virtual reality (VR) based PA programs, but there is a lack of research evidence. AIM: We aimed to examine the effect of a VR-based PA program on motor skills and PA levels in children with DD. METHODS AND PROCEDURES: Twenty-three children with DD were randomly assigned to an experimental and a control group. The intervention was conducted for 24 sessions, 40 min each, and twice a week. Each participant rode a stationary bike with a cadence sensor wearing a VR headset. TGMD-3 and a GENEActiv accelerometer were used to measure motor skills and PA levels one week before and after the intervention. OUTCOMES AND RESULTS: Children in the experimental group showed a significant increase in locomotor skills. Ball skills also increased but did not have significant differences. For PA levels, both groups did not have significant increase after the intervention. CONCLUSIONS AND IMPLICATIONS: A VR-based PA program was effective in improving locomotor skills among children with DD. To significantly change ball skills and PA levels of children with DD, VR-based PA program mixed with reality-based PA program is probably necessary.

Lien vers le texte intégral (Open Access ou abonnement)

8. Lefebvre A, Tillmann J, Cliquet F, Amsellem F, Maruani A, Leblond C, Beggiato A, Germanaud D, Amestoy A, Ly-Le Moal M, Umbricht D, Chatham C, Murtagh L, Bouvard M, Leboyer M, Charman T, Bourgeron T, Delorme R, Dumas G. Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways. Autism research : official journal of the International Society for Autism Research. 2022.

As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data. To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0. However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum.

Lien vers le texte intégral (Open Access ou abonnement)

9. Li YA, Chen ZJ, Li XD, Gu MH, Xia N, Gong C, Zhou ZW, Yasin G, Xie HY, Wei XP, Liu YL, Han XH, Lu M, Xu J, Huang XL. Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors. Frontiers in pediatrics. 2022; 10: 972809.

BACKGROUND: To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD. METHODS: In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace. RESULTS: Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. « Rehabilitation », « Genetics & Heredity », « Nanoscience & Nanotechnology », « Biochemistry & Molecular biology », « Psychology », « Neurosciences », and « Environmental Sciences » were the hotspots and frontier disciplines of ASD risk factors. CONCLUSIONS: Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.

Lien vers le texte intégral (Open Access ou abonnement)

10. Rivard M, Mestari Z, Coulombe P, Morin D, Mello C, Morin M. Developmental and behavioral groupings can predict changes in adaptive behavior over time in young children with neurodevelopmental disorders. Research in developmental disabilities. 2023; 132: 104390.

The heterogeneity within, and the overlap between, diagnostic categories for neurodevelopmental disorders (NDDs) remain poorly understood. Developmental trajectories may diverge among children with the same diagnosis, who may also respond very differently to treatment. In a previous study, we used statistical clustering methods in a sample of 194 preschoolers who were referred for NDD assessment. We identified three distinct subgroups based on multiple developmental and behavioral variables. The present study aimed to identify: (1) early developmental markers at the surveillance and screening period that are predictive of subgroup membership at the diagnostic period (i.e., around age 5), (2) associations between subgroups and the evolution of adaptive behavior over the course of two years, and (3) predictors of adaptive behavior change. Subgroup membership was the only significant predictor of adaptive behavior change over time, which suggests that a clustering method based on developmental and behavioral profiles may be useful in treatment planning.

Lien vers le texte intégral (Open Access ou abonnement)

11. Smith AA, Forero M, Finkelman MD, Dolan K. A dental desensitization program for children with autism spectrum disorder. Journal of dental education. 2022.

Lien vers le texte intégral (Open Access ou abonnement)

12. Suzuki T, Ito Y, Ito T, Kidokoro H, Noritake K, Tsujimura K, Saitoh S, Yamamoto H, Ochi N, Ishihara N, Yasui I, Sugiura H, Nakata T, Natsume J. Pathological gait in Rett syndrome: Quantitative evaluation using three-dimensional gait analysis. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2022; 42: 15-21.

OBJECTIVES: Ataxic-rigid gait is a characteristic gait pathology in patients with Rett syndrome (RTT). In the present study, we aimed to quantitatively evaluate gait pathology in patients with RTT using three-dimensional gait analysis (3DGA). METHODS: We performed 3DGA in 11 patients with RTT ranging from 5 to 18 years (median age, 9 years) and in 33 age-matched healthy female controls. We compared the results of 3DGA, including spatiotemporal gait parameters and comprehensive indices of gait kinematics, such as the Gait Deviation Index (GDI) and Gait Profile Score (GPS), between the two groups. The GPS consists of nine sub-indices called Gait Variable Scores (GVSs). Decline in GDI or elevation of GPS and GVS indicated greater abnormal gait pathology. RESULTS: The patients demonstrated significantly slower walking speed, lower step length/length of the lower extremities, lower cadence, wider step width, and higher coefficient of variation of step length than the controls. Moreover, the patients had a lower GDI and higher GPS than the controls. The patients also exhibited higher GVSs for eight out of nine gait kinematics, particularly the sagittal plane in the pelvis, hip, knee, and ankle joint; coronal plane in the pelvis and hip joint; and horizontal plane in the pelvis than the controls. CONCLUSIONS: Quantitative evaluation of gait pathology in patients with RTT is possible using 3DGA. We found that in addition to ataxic-rigid gait, abnormalities in the coronal plane of the pelvis and hip joint and the horizontal plane of the pelvis were prominent.

Lien vers le texte intégral (Open Access ou abonnement)

13. Vodakova E, Chatziioannou D, Jesina O, Kudlacek M. The Effect of Halliwick Method on Aquatic Skills of Children with Autism Spectrum Disorder. International journal of environmental research and public health. 2022; 19(23).

BACKGROUND: Swimming and the skills associated with participation in the aquatic environment tend to be an integral part of the movement literacy complex. Non-participation then affects the safety of movement in the aquatic environment and may also be the reason for the limitation of movement, psychological, and social development compared to peers. METHODS: This study is a single-subject research study. The aim of this study is to evaluate the effect of a seven-week intervention program of the Halliwick method in the development of aquatic skills, gross motor skills, and mental skills relevant for aquatic competence for children with autism spectrum disorder. Seven children with autism spectrum disorder participated in swimming classes for a two-week baseline period and a seven-week intervention program of the Halliwick method, one time per week. To measure the effect in the field of aquatic skills, we used the Alyn Water Orientation Test 1. To determine the level of gross motor skills, we used the Gross Motor Function Measure test. RESULTS: There was an improvement in aquatic skills and gross motor skills in seven participants; two of them did not improve in mental adjustment oriented to the breathing control sections in the water.

Lien vers le texte intégral (Open Access ou abonnement)

14. Yang L, Lu S, Yang Z, Yao J, Zhou P, Zhao M. Generation of an induced pluripotent stem cell line (IPCASi001-A) from an autism spectrum disorder individual without intellectual disability. Stem cell research. 2022; 66: 102994.

Autism spectrum disorder (ASD) is a highly inheritable neurodevelopmental disorder that causes diverse deficits in social communication and restricted repetitive sensorimotor behaviors. Here, we studied a human-induced pluripotent cell line from an autistic patient with impaired social function and a normal intelligence quotient (IQ > 70). The cell line was validated by its morphology, gene expression, and potential to differentiate into three germ layers. This model can be used to explore the pathophysiological and molecular mechanisms in patients with ASD, compared those of with patients with normal cognitive abilities.

Lien vers le texte intégral (Open Access ou abonnement)

15. Zhong T, Liu H, Li Y, Qi J. Correlates of Physical Activity of Children and Adolescents with Autism Spectrum Disorder in Low- and Middle-Income Countries: A Systematic Review of Cross-Sectional Studies. International journal of environmental research and public health. 2022; 19(23).

Children and adolescents with autism spectrum disorder (ASD) are at a high risk for a lack of physical activity (PA). The aim of this study is to review the evidence on the correlates of PA in children and adolescents with ASD in low- and middle-income countries. We searched Psychology and Behavioral Sciences Collection (PBSC), Scopus, PsycINFO, Web of Science (WOS), MEDLINE, Education Resources Information Center (ERIC), Education Source (ES), and Academic Search Premier (ASP) databases for relevant studies until April 2022, inclusive, to examine the factors associated with the studies of PA in children and adolescents with ASD aged 5 to 17 years in low- and middle-income countries. A total of 15 articles are included in the present review. Three researchers assessed the methodological quality and extracted relevant data of the included reviews. The correlates were synthesized and further assessed semi-quantitatively. Results of this review show that gender (boys) and more PA opportunities were positively associated with the PA of children and adolescents with ASD, while age and body mass index (BMI) were negatively related to their PA levels in low- and middle-income countries. The day of week was found to be inconsistently associated with PA in children and adolescents with ASD. The findings suggest that research on the correlates of PA in adolescents with ASD in low- and middle-income countries is limited. However, there are clear correlates for which future interventions could be based (age, gender, BMI, and PA opportunity) to promote PA participation in children and adolescents with ASD in low- and middle-income countries.

Lien vers le texte intégral (Open Access ou abonnement)