Pubmed du 13/12/19

vendredi 13 décembre 2019

1. Arciuli J, Colombo L, Surian L. Lexical stress contrastivity in Italian children with autism spectrum disorders : an exploratory acoustic study. J Child Lang. 2019 : 1-11.

We investigated production of lexical stress in children with and without autism spectrum disorders (ASD), all monolingual Italian speakers. The mean age of the 16 autistic children was 5.73 years and the mean age of the 16 typically developing children was 4.65 years. Picture-naming targets were five trisyllabic words that began with a weak-strong pattern of lexical stress across the initial two syllables (WS : matita) and five trisyllabic words beginning with a strong-weak pattern (SW : gomito). Acoustic measures of the duration, fundamental frequency, and intensity of the first two vowels for correct word productions were used to calculate a normalised Pairwise Variability Index (PVI) for WS and SW words. Results of acoustic analyses indicated no statistically significant group differences in PVIs. Results should be interpreted in line with the exploratory nature of this study. We hope this study will encourage additional cross-linguistic studies of prosody in children’s speech production.

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2. Arslan M, Warreyn P, Dewaele N, Wiersema JR, Demurie E, Roeyers H. Development of neural responses to hearing their own name in infants at low and high risk for autism spectrum disorder. Developmental cognitive neuroscience. 2019 ; 41 : 100739.

The own name is a salient stimulus, used by others to initiate social interaction. Typically developing infants orient towards the sound of their own name and exhibit enhanced event-related potentials (ERP) at 5 months. The lack of orientation to the own name is considered to be one of the earliest signs of autism spectrum disorder (ASD). In this study, we investigated ERPs to hearing the own name in infants at high and low risk for ASD, at 10 and 14 months. We hypothesized that low-risk infants would exhibit enhanced frontal ERP responses to their own name compared to an unfamiliar name, while high-risk infants were expected to show attenuation or absence of this difference in their ERP responses. In contrast to expectations, we did not find enhanced ERPs to own name in the low-risk group. However, the high-risk group exhibited attenuated frontal positive-going activity to their own name compared to an unfamiliar name and compared to the low-risk group, at the age of 14 months. These results suggest that infants at high risk for ASD start to process their own name differently shortly after one year of age, a period when frontal brain development is happening at a fast rate.

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3. Ciranna L, Costa L. Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Hippocampal Synaptic Transmission and Plasticity : New Therapeutic Suggestions for Fragile X Syndrome. Frontiers in cellular neuroscience. 2019 ; 13 : 524.

Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates glutamatergic synaptic transmission and plasticity in the hippocampus, a brain area with a key role in learning and memory. In agreement, several studies have demonstrated that PACAP modulates learning in physiological conditions. Recent publications show reduced PACAP levels and/or alterations in PACAP receptor expression in different conditions associated with cognitive disability. It is noteworthy that PACAP administration rescued impaired synaptic plasticity and learning in animal models of aging, Alzheimer’s disease, Parkinson’s disease, and Huntington’s chorea. In this context, results from our laboratory demonstrate that PACAP rescued metabotropic glutamate receptor-mediated synaptic plasticity in the hippocampus of a mouse model of fragile X syndrome (FXS), a genetic form of intellectual disability. PACAP is actively transported through the blood-brain barrier and reaches the brain following intranasal or intravenous administration. Besides, new studies have identified synthetic PACAP analog peptides with improved selectivity and pharmacokinetic properties with respect to the native peptide. Our review supports the shared idea that pharmacological activation of PACAP receptors might be beneficial for brain pathologies with cognitive disability. In addition, we suggest that the effects of PACAP treatment might be further studied as a possible therapy in FXS.

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4. Engel CS, Sheppard E. Can Cartoons Which Depict Autistic Characters Improve Attitudes Towards Autistic Peers ?. J Autism Dev Disord. 2019.

This study aimed to assess the efficacy of two cartoons which depict autistic characters in improving attitudes towards autistic peers in two separate studies. Forty-six children participated in study 1 (4-7 years), and 47 children participated in study 2 (8-11 years). Both the conative (behavioural) component of attitudes and knowledge about autism were measured before and after the cartoon interventions. Knowledge of autism increased after watching the cartoons in both studies but attitudes to autism only improved in study 1. Knowledge was shown to correlate with change in some but not all attitude measures. The findings suggest that cartoons can improve attitudes to autism, but this may depend on how information is presented.

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5. Eslami T, Mirjalili V, Fong A, Laird AR, Saeed F. ASD-DiagNet : A Hybrid Learning Approach for Detection of Autism Spectrum Disorder Using fMRI Data. Frontiers in neuroinformatics. 2019 ; 13 : 70.

Heterogeneous mental disorders such as Autism Spectrum Disorder (ASD) are notoriously difficult to diagnose, especially in children. The current psychiatric diagnostic process is based purely on the behavioral observation of symptomology (DSM-5/ICD-10) and may be prone to misdiagnosis. In order to move the field toward more quantitative diagnosis, we need advanced and scalable machine learning infrastructure that will allow us to identify reliable biomarkers of mental health disorders. In this paper, we propose a framework called ASD-DiagNet for classifying subjects with ASD from healthy subjects by using only fMRI data. We designed and implemented a joint learning procedure using an autoencoder and a single layer perceptron (SLP) which results in improved quality of extracted features and optimized parameters for the model. Further, we designed and implemented a data augmentation strategy, based on linear interpolation on available feature vectors, that allows us to produce synthetic datasets needed for training of machine learning models. The proposed approach is evaluated on a public dataset provided by Autism Brain Imaging Data Exchange including 1, 035 subjects coming from 17 different brain imaging centers. Our machine learning model outperforms other state of the art methods from 10 imaging centers with increase in classification accuracy up to 28% with maximum accuracy of 82%. The machine learning technique presented in this paper, in addition to yielding better quality, gives enormous advantages in terms of execution time (40 min vs. 7 h on other methods). The implemented code is available as GPL license on GitHub portal of our lab (

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6. Genez M. Septic Pulmonary Embolism Associated with Klebsiella spp. Infection in a Patient with Previous ASD Operation. Turkish journal of anaesthesiology and reanimation. 2019 ; 47(6) : 511-4.

Septic pulmonary embolism (SPE) is an uncommon disease caused by thromboembolism associated with microorganisms. A 57-year old woman patient who was monitored for a prediagnosis of subileus suffered from sudden respiration problems in the hospital ward. The patient’s history included atrial fibrillation and atrioseptal defect (ASD) operation. The patient was admitted to the intensive care unit (ICU) in order to apply non-invasive mechanical ventilation and keep her under observation because of low saturation and loss of consciousness. In the ICU, the patient’s temperature was 38.8 degrees C, which led to the diagnosis of sepsis. The chest X-ray showed bilateral and multiple patchy infiltrates. The thorax CT showed right lower pulmonary consolidation and left pulmonary pleuroparenchymal density with nodular shapes. The electrocardiogram showed mild pulmonary hypertension and third-degree tricuspid failure. These features indicated SPE because of the ASD operation in the past. The blood culture showed the presence of Klebsiella spp., which is uncommon. A characteristic CT sign is very important for the early diagnosis and treatment of SPE.

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7. Gottlieb MM. Mathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in Autism. Computational and mathematical methods in medicine. 2019 ; 2019 : 7308197.

This paper develops mathematical models examining possible roles of oxytocin and oxytocin receptors in the development of autism. This is done by demonstrating that mathematical operations on normalized data from the Stanford study, which establishes a correspondence between severity of autism in children and their oxytocin blood levels, generate a graph that is the same as the graph of mathematical operations on a normalized theoretical model for the severity of autism. This procedure establishes the validity of the theoretical model and the significance of oxytocin receptors in autism. A steady-state model follows, explaining the constant baseline concentrations of oxytocin observed in the cerebral spinal fluid and blood in terms of the neuromodulation by oxytocin of oxytocin receptors on the magnocellular neurons that produce oxytocin in nuclei in the hypothalamus. The implications of these models for possible roles of oxytocin and oxytocin receptors in autism are considered for several unrelated conditions that may be associated with autism. These are oxytocin receptor desensitization and downregulation as factors during labor in offspring autism development ; reductions in the oxytocin receptor numbers in the fixed oxytocin receptor expression that occurs before birth ; MAST Immune System disease ; and the excess number of dendritic spines from lack of pruning observed in brains of autistic people. Research into the feasibility of generating magnocellular neurons and other neurons from adult stem cells is suggested as a way of doing in vitro studies of oxytocin and oxytocin receptors to assess the validity of theories presented in this paper.

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8. Heald M, Adams D, Oliver C. Profiles of atypical sensory processing in Angelman, Cornelia de Lange and Fragile X syndromes. J Intellect Disabil Res. 2019.

BACKGROUND : There is growing evidence to suggest that children with neurodevelopmental disorders may evidence differences in their sensory processing. The aim of this study was to compare sensory processing patterns in three genetic syndromes associated with sensory difference. METHODS : Sensory processing in Angelman syndrome (n = 91), Cornelia de Lange syndrome (n = 28) and Fragile X syndrome (n = 40) was examined using the informant report measure the Sensory Experiences Questionnaire (SEQ). RESULTS : All three groups were associated with a heightened prevalence of unusual sensory processing in comparison with normative data, evidenced in over 80% of all participants. Cross-syndrome comparisons highlighted syndrome-specific sensory processing profiles, with heightened hypo responsivity in Cornelia de Lange syndrome and sensory seeking in Angelman syndrome. CONCLUSIONS : The results have important implications for the understanding of sensory processing in genetic syndromes and the development of tailored behavioural interventions.

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9. Marcotte J, Grandisson M, Piquemal C, Boucher A, Rheault ME, Milot E. Supporting Independence at Home of People with Autism Spectrum Disorder : Literature Review. Canadian journal of occupational therapy Revue canadienne d’ergotherapie. 2019 : 8417419890179.

BACKGROUND. : The integration of a life environment enabling people with autism spectrum disorder (ASD) to fully exercise their independence must be well prepared. PURPOSE. : Review and describe interventions intended to develop the independence at home of people with ASD. METHOD. : The PRISMA method was used to perform a systematic review based on 19 keywords, grouped under three concepts : (a) population age (adolescents and adults), (b) diagnosis (ASD), and (c) independence. FINDINGS. : Seven effective interventions were identified in the 20 selected articles : (a) video self-modeling, (b) video modeling, (c) behavioural interventions, (d) video prompting, (e) transition planning program, (f) training in the use of a cognitive aid, and (g) social skills group. IMPLICATIONS. : The results of this review will help guide practitioners in the implementation of interventions that foster the development of independence at home of people with ASD.

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10. McClain MB, Harris B, Haverkamp CR, Golson ME, Schwartz SE. The ASKSP Revised (ASKSP-R) as a Measure of ASD Knowledge for Professional Populations. J Autism Dev Disord. 2019.

It is important for all professionals who work with individuals who have ASD to have sufficient knowledge of the disorder. The development of ASD knowledge may occur during preservice training and/or through professional development. Currently, there is no "gold standard" measure of ASD knowledge. A study focusing on the development of a reliable and valid measure of ASD knowledge for practitioners and preservice professionals is warranted. To address this need, the current study provides preliminary information on the development and preliminary validation of the Autism Spectrum Knowledge Scale Professional Version-Revised (ASKSP-R) with a sample of school-based professionals (N = 427). Results suggest the ASKSP-R is a univariate measure with good reliability. Implications and suggestions for future research are discussed.

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11. Mohammadi F, Rakhshan M, Molazem Z, Gillespie M. Parental Competence in Parents of Children with Autism Spectrum Disorder : A Systematic Review. Investigacion y educacion en enfermeria. 2019 ; 37(3).

OBJECTIVES : This work aimed to define and assess the parental competence of parents with autistic children. METHODS : This study was conducted through a systematic review. The search was done in databases, including Cochrane Library, PubMed, CINAHL, Science Direct, Wiley Scopus, Pro Quest, Web of Science, Elsevier, Google Scholar, and Ovid by using keywords, like "children, autism, parenting, competence, and scale" from 1974 to 2019. Inclusion criteria were that the article should be quantitative, qualitative, and mixed-method studies in nursing, psychology, and medicine ; the full text of the article should be available and the article should be in English or Persian. RESULTS : Competence among these parents was affected by more factors and they reported lower competence compared to other parents. Moreover, only two instruments were available to assess parenting competence, which were not designed for parents of autistic children. Variables and factors affecting parenting competence has not been examined well in parents of children with autism, and no specialized instrument is available to evaluate parenting competence in parents with autistic children either. CONCLUSIONS : Although parental competence has been known as the main element to improve the quality of care, it has been studied restrictively from the viewpoints of the parents of children with autism. Therefore, the development of this concept is highly essential for clinical application and investigating its outcomes support.

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12. Nilses A, Jingrot M, Linnsand P, Gillberg C, Nygren G. Experiences Of Immigrant Parents In Sweden Participating In A Community Assessment And Intervention Program For Preschool Children With Autism. Neuropsychiatr Dis Treat. 2019 ; 15 : 3397-410.

Background : Barriers inherent in service systems for autism can hinder parents from getting help for their children, and this is probably especially true for immigrant parents. In order to provide accessible assessment and interventions for preschool children with autism, a multidisciplinary team was established in one district of a Swedish city, with a majority population of immigrants. Aim : The aim of the present study was to gain knowledge of the parents’ experiences of participating in the community assessment and intervention program. Methods and procedures : A qualitative study with semi-structured interviews was conducted with parents of 11 children aged 3-5, who had been diagnosed with autism and participated in the community intervention program for at least 1 year. The interviews were recorded and transcribed verbatim, and data were analyzed following a phenomenological hermeneutical method. Results : The overall meaning of the parents’ narratives was interpreted as "A new way of understanding my child made life more hopeful and more challenging than before". Their experience was interpreted as a process, captured in the three main themes : "An overwhelming diagnosis", "Cooperating with the team", and "Growing as a parent". Conclusion : As lacking knowledge of available resources and support seems to be an important barrier to access services, the results underscore the importance of providing individually tailored services including comprehensive societal support to immigrant families with young children suffering from autism. The study also highlights the importance of addressing the parents’ previous awareness and knowledge of autism early in the assessment process, as well as continually involving parents in the intervention program, and this may enhance parental growth.

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13. Pirooznia M, Niranjan T, Chen YC, Tunc I, Goes FS, Avramopoulos D, Potash JB, Huganir RL, Zandi PP, Wang T. Affected Sib-Pair Analyses Identify Signaling Networks Associated With Social Behavioral Deficits in Autism. Front Genet. 2019 ; 10 : 1186.

Autism spectrum disorders (ASDs) are characterized by deficits in three core behavioral domains : reciprocal social interactions, communication, and restricted interests and/or repetitive behaviors. Several hundreds of risk genes for autism have been identified, however, it remains a challenge to associate these genes with specific core behavioral deficits. In multiplex autism families, affected sibs often show significant differences in severity of individual core phenotypes. We hypothesize that a higher mutation burden contributes to a larger difference in the severity of specific core phenotypes between affected sibs. We tested this hypothesis on social behavioral deficits in autism. We sequenced synaptome genes (n = 1,886) in affected male sib-pairs (n = 274) in families from the Autism Genetics Research Exchange (AGRE) and identified rare (MAF /=10 ; n = 92 pairs) or a small (/=10 compared to SOCT_CS /=10 : 705.1 +/- 16.2 ; SOCT_CS /=10 genes only in sibs with severe social deficits are significantly enriched in the SFARI gene set. Network analyses of these genes using InWeb_IM, molecular signatures database (MSigDB), and GeNetMeta identified enrichment for phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) (Enrichment Score [eScore] p value = 3.36E-07 ; n = 8 genes) and Nerve growth factor (NGF) (eScore p value = 8.94E-07 ; n = 9 genes) networks. These studies support a key role for these signaling networks in social behavioral deficits and present a novel approach to associate risk genes and signaling networks with core behavioral domains in autism.

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14. Rohr CS, Kamal S, Bray S. Building functional connectivity neuromarkers of behavioral self-regulation across children with and without Autism Spectrum Disorder. Developmental cognitive neuroscience. 2019 ; 41 : 100747.

Behavioral self-regulation develops rapidly during childhood and struggles in this area can have lifelong negative outcomes. Challenges with self-regulation are common to several neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). Little is known about the neural expression of behavioral regulation in children with and without neurodevelopmental conditions. We examined whole-brain brain functional correlations (FC) and behavioral regulation through connectome predictive modelling (CPM). CPM is a data-driven protocol for developing predictive models of brain-behavior relationships and assessing their potential as ’neuromarkers’ using cross-validation. The data stems from the ABIDE II and comprises 276 children with and without ASD (8-13 years). We identified networks whose FC predicted individual differences in behavioral regulation. These network models predicted novel individuals’ inhibition and shifting from FC data in both a leave-one-out, and split halves, cross-validation. We observed commonalities and differences, with inhibition relying on more posterior networks, shifting relying on more anterior networks, and both involving regions of the DMN. Our findings substantially add to our knowledge on the neural expressions of inhibition and shifting across children with and without a neurodevelopmental condition. Given the numerous behavioral issues that can be quantified dimensionally, refinement of whole-brain neuromarker techniques may prove useful in the future.

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15. Sjaarda CP, Wood S, McNaughton AJM, Taylor S, Hudson ML, Liu X, Guerin A, Ayub M. Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism. Journal of human genetics. 2019.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneity in presentation, genetic etiology, and clinical outcome. Although numerous ASD susceptibility genes have been described, they only account for a small fraction of the estimated heritability, supporting the need to identify more risk variants. This study reports the whole exome sequencing for 24 simplex families with sporadic cases of ASD. These families were selected following a rigorous family history study designed to exclude families with any history of neurodevelopmental or psychiatric disease. Fifteen rare, de novo variants, including fourteen missense variants and one splicing variant, in thirteen families were identified. We describe a splicing variant in XRCC6 which was predicted to destroy the 5’ splice site in intron 9 and introduce a premature stop codon. We observed intron 9 retention in XRCC6 transcripts and reduced XRCC6 expression in the proband. Reduced XRCC6 activity and function may be relevant to ASD etiology due to XRCC6’s role in nonhomologous DNA repair and interactions of the C-terminal SAP domain with DEAF1, a nuclear transcriptional regulator that is important during embryonic development.

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16. van Kessel R, Roman-Urrestarazu A, Ruigrok A, Holt R, Commers M, Hoekstra RA, Czabanowska K, Brayne C, Baron-Cohen S. Autism and family involvement in the right to education in the EU : policy mapping in the Netherlands, Belgium and Germany. Mol Autism. 2019 ; 10 : 43.

Introduction : In recent years, the universal right to education has been emphasised by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies relevant to special education needs and parental involvement of children with autism at an international level and in the Netherlands, Germany and Belgium. Methods : A policy path analysis was performed using a scoping review as an underlying methodological framework. This allowed for a rapid gathering of available data from which a timeline of adopted policies was derived. Results and discussion : Internationally, the universal right to education has been reinforced repeatedly and the values of the Universal Declaration of Human Rights have been reiterated with every reinforcement. Also, the additional support that a child with special education needs requires is acknowledged and measures are taken to facilitate access to any education for all children. There are slight cross-country differences between the countries under study, attributable to differences in national regulation of education. However, all countries have progressed to a state where the right to education for all children is integrated on a policy level and measures are taken to enable children with special needs to participate in education. Recently, an attempt to implement a form of inclusive education was made as a form of special needs provision. Nevertheless, nowhere has this been implemented successfully yet. Conclusion : The Universal Declaration of Human Rights was a critical juncture in international policy and created an environment where the universal right to education has been implemented for all children in the countries under study.

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17. Yi H, Siu QKY, Ngan OMY, Chan DFY. Parents’ experiences of screening, diagnosis, and intervention for children with autism spectrum disorder. The American journal of orthopsychiatry. 2019.

This mixed-methods study aimed to explore the experiences of screening, assessment, diagnosis, and intervention for autism spectrum disorder (ASD) among 249 parents of children with ASD in Hong Kong. Participants completed a survey and responded to open-ended questions regarding their experiences and views of ASD service provision. The quantitative analysis focused on (a) assessing parents’ experiences of key milestones, including the time to access, professional support and consultation, referral and follow-up, and (b) examining the correlates of the milestone experiences. Qualitative themes focused on the contexts of parents’ difficulties and views of ASD service provision. A joint display presented the integration of converging the quantitative and qualitative data. There were significant delays from screening and diagnosis to intervention due to limited resources for ASD. Although the government surveillance system facilitated access to screening, a delay in the entry to intervention remained. Parents’ narratives of frustration and confusion with ASD services reflected a lack of a coherent system for diagnosis and family needs assessment. Quality service provision for ASD requires integrated efforts of early identification, referral, and psychoeducational family support. Unbalanced resources between screening and intervention in public pediatric care settings should be addressed to meet the unmet needs of children with ASD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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18. Zhu JW, Zou MM, Li YF, Chen WJ, Liu JC, Chen H, Fang LP, Zhang Y, Wang ZT, Chen JB, Huang W, Li S, Jia WQ, Wang QQ, Zhen XC, Liu CF, Li S, Xiao ZC, Xu GQ, Schwamborn JC, Schachner M, Ma QH, Xu RX. Absence of TRIM32 Leads to Reduced GABAergic Interneuron Generation and Autism-like Behaviors in Mice via Suppressing mTOR Signaling. Cereb Cortex. 2019.

Mammalian target of rapamycin (mTOR) signaling plays essential roles in brain development. Hyperactive mTOR is an essential pathological mechanism in autism spectrum disorder (ASD). Here, we show that tripartite motif protein 32 (TRIM32), as a maintainer of mTOR activity through promoting the proteasomal degradation of G protein signaling protein 10 (RGS10), regulates the proliferation of medial/lateral ganglionic eminence (M/LGE) progenitors. Deficiency of TRIM32 results in an impaired generation of GABAergic interneurons and autism-like behaviors in mice, concomitant with an elevated autophagy, which can be rescued by treatment embryonically with 3BDO, an mTOR activator. Transplantation of M/LGE progenitors or treatment postnatally with clonazepam, an agonist of the GABAA receptor, rescues the hyperexcitability and the autistic behaviors of TRIM32-/- mice, indicating a causal contribution of GABAergic disinhibition. Thus, the present study suggests a novel mechanism for ASD etiology in that TRIM32 deficiency-caused hypoactive mTOR, which is linked to an elevated autophagy, leads to autism-like behaviors via impairing generation of GABAergic interneurons. TRIM32-/- mouse is a novel autism model mouse.

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