Pubmed du 31/07/20

vendredi 31 juillet 2020

1. Bentz M, Westwood H, Jepsen JRM, Plessen KJ, Tchanturia K. The autism diagnostic observation schedule : Patterns in individuals with anorexia nervosa. Eur Eat Disord Rev ;2020 (Jul 29)

OBJECTIVE : Studies have used the Autism Diagnostic Observation Schedule (the ADOS-2) in individuals with anorexia nervosa (AN), but the patterns of scores have not been assessed. We examined which subset of the ADOS-2 items best discriminate individuals with AN from healthy controls (HC), and assessed the potential clustering of AN participants based on different profiles of the ADOS-2 item scores. METHOD : We combined datasets from two previous studies, and (a) compared mean ranks between young AN participants (N = 118) and HC (N = 42), (ii) replicated the item selection procedure of the existing ADOS-2 algorithm to assess sensitivity of items in the AN group, and (c) applied a two-step clustering analysis in the AN group (N = 149). RESULTS : AN participants displayed significantly higher mean ranks than HC participants in five of 32 items. All five items are part of the existing ADOS-2 algorithm. We found two clusters of AN participants ; one representing normal social behaviour, comprising 68% of the individuals with AN, and one representing less efficient social behaviour, comprising 32% of individuals with AN. CONCLUSIONS : The items comprising the social affective cluster of the existing ADOS-2 algorithm are well suited to assess difficulties with social functioning in individuals with AN.

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2. Brewe AM, Mazefsky CA, White SW. Therapeutic Alliance Formation for Adolescents and Young Adults with Autism : Relation to Treatment Outcomes and Client Characteristics. J Autism Dev Disord ;2020 (Jul 31)

Therapeutic alliance may influence treatment outcomes for individuals with autism spectrum disorder (ASD). The present study examined the trajectory of alliance, observationally-measured at four timepoints during a 16-week mindfulness-based treatment targeting emotion regulation problems in adolescents and young adults with ASD (n = 37, mean age = 15.28, 78.40% male). Variability in alliance as a function of client characteristics and the degree to which alliance predicted emotion regulation outcomes were assessed using parent-report forms. Results demonstrate that alliance fluctuates throughout treatment. Moreover, stronger alliance predicts decreased dysphoria at posttreatment. Results also suggest that increased ASD symptom severity and depression predict weaker alliance early and throughout treatment. Findings highlight a need for clinicians to consider the importance of developing strong alliance for clients with ASD.

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3. Chen L, Chen Y, Zheng H, Zhang B, Wang F, Fang J, Li Y, Chen Q, Zhang S. Changes in the topological organization of the default mode network in autism spectrum disorder. Brain Imaging Behav ;2020 (Jul 31)

Neuroimaging studies have demonstrated that autism spectrum disorder (ASD) is accompanied by abnormal functional and structural features in specific brain regions of the default mode network (DMN). However, little is known about the alterations of the topological organization and the functional connectivity (FC) of the DMN in ASD patients. Thirty-seven ASD patients and 38 healthy control (HC) participants underwent a resting-state functional magnetic resonance imaging scan. Twenty DMN subregions were specifically selected to construct the DMN architecture. We applied graph theory approaches to the topological configuration and compare the FC patterns of the DMN. We then examined the relationships between the neuroimaging measures of the DMN and clinical characteristics in patients with ASD. The current study revealed that both the ASD and HC participants showed a small-world regimen in the DMN ; however there were no significant differences in global network measures. Compared with the HC group, the ASD group exhibited significantly decreased nodal centralities in the bilateral anterior medial prefrontal cortex and increased nodal centralities in the right lateral temporal cortex and the right retrosplenial cortex. Patients with ASD displayed significantly reduced and increased FC within the DMN. Our findings demonstrated that ASD patients showed a pattern of disrupted FC metrics and nodal network metrics in the DMN, which could be a potential biomarker for objective ASD diagnoses and for the level of autism spectrum traits. HIGHLIGHTS : We used graph theoretical approaches and functional connectivity (FC) to investigate the topological configuration and FC patterns of the DMN in ASD. The current study revealed that both ASD and HC participants exhibited small-world regimes in the DMN, however there were no significant differences in global network measures. The ASD group showed abnormal nodal centralities in the bilateral aMPFC, the right LTC and the Rsp of the DMN, and ASD was characterized by altered FC patterns, including decreased and increased FC within the DMN.

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4. Crane L, Sesterka A, den Houting J. Inclusion and Rigor in Qualitative Autism Research : A Response to Van Schalkwyk and Dewinter (2020). J Autism Dev Disord ;2020 (Jul 31)

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5. Custer TN, Stiehl CM, Lerman DC. Outcomes of a practical approach for improving conversation skills in adults with autism. J Appl Behav Anal ;2020 (Jul 31)

Many individuals with autism spectrum disorder (ASD) have deficits in conversation skills that can interfere with the development of personal and professional relationships. Further research is needed on efficient interventions for targeting conversation skills in adults with ASD and for evaluating the social validity of the outcomes. In this study, 2 practitioners implemented a 4-week training program for 5 adults with ASD that combined individualized computer-based instruction (CBI) and practice with peers to promote the acquisition, maintenance, and generalization of conversation skills. Training was associated with improvements in 12 of 13 skills across participants. These findings, along with peer ratings of the participants’ conversation skills, suggest that this model is a promising, socially valid approach for improving conversation skills in adults with ASD.

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6. Damiani S, Leali P, Nosari G, Caviglia M, Puci MV, Monti MC, Brondino N, Politi P. Association of Autism Onset, Epilepsy, and Behavior in a Community of Adults with Autism and Severe Intellectual Disability. Brain Sci ;2020 (Jul 27) ;10(8)

Autism spectrum disorders (ASDs) are hard to characterize due to their clinical heterogeneity. Whether epilepsy and other highly prevalent comorbidities may be related to specific subphenotypes such as regressive ASD (i.e., the onset of symptoms after a period of apparently typical development) is controversial and yet to be determined. Such discrepancies may be related to the fact that age, level of cognitive functioning, and environmental variables are often not taken into account. We considered a sample of 20 subjects (i) between 20 and 55 years of age, (ii) with severe/profound intellectual disability, (iii) living in the same rural context of a farm community. As a primary aim, we tested for the association between epilepsy and regressive ASD. Secondly, we explored differences in behavioral and pharmacological profiles related to the presence of each of these conditions, as worse behavioral profiles have been separately associated with both epilepsy and regressive ASD in previous studies. An initial trend was observed for associations between the presence of epilepsy and regressive ASD (odds ratio : 5.33 ; 95% CI : 0.62-45.41, p-value : 0.086). Secondly, subjects with either regressive ASD or epilepsy showed worse behavioral profiles (despite the higher pharmacotherapy they received). These preliminary results, which need to be further confirmed, suggest the presence of specific associations of different clinical conditions in subjects with rarely investigated phenotypes.

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7. De Korte MW, van den Berk-Smeekens I, van Dongen-Boomsma M, Oosterling IJ, Den Boer JC, Barakova EI, Lourens T, Buitelaar JK, Glennon JC, Staal WG. Self-initiations in young children with autism during Pivotal Response Treatment with and without robot assistance. Autism ;2020 (Jul 30):1362361320935006.

The initiation of social interaction is often defined as a core deficit of autism spectrum disorder. Optimizing these self-initiations is therefore a key component of Pivotal Response Treatment, an established intervention for children with autism spectrum disorder. However, little is known about the development of self-initiations during intervention and whether this development can be facilitated by robot assistance within Pivotal Response Treatment. The aim of this study was to (1) investigate the effect of Pivotal Response Treatment and robot-assisted Pivotal Response Treatment on self-initiations (functional and social) of young children with autism spectrum disorder over the course of intervention and (2) explore the relation between development in self-initiations and additional gains in general social-communicative skills. Forty-four children with autism spectrum disorder (aged 3-8 years) were included in this study. Self-initiations were assessed during parent-child interaction videos of therapy sessions and coded by raters who did not know which treatment (Pivotal Response Treatment or robot-assisted Pivotal Response Treatment) the child received. General social-communicative skills were assessed before start of the treatment, after 10 and 20 weeks of intervention and 3 months after the treatment was finalized. Results showed that self-initiations increased in both treatment groups, with the largest improvements in functional self-initiations in the group that received robot-assisted Pivotal Response Treatment. Increased self-initiations were related to higher parent-rated social awareness 3 months after finalizing the treatment.

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8. Fredo ARJ, Thomas J, Prasanth T, Vineetha K, Langs G, Dauwels J. Diagnostic classification of autism using resting-state fMRI data improves with full correlation functional brain connectivity compared to partial correlation. J Neurosci Methods ;2020 (Jul 27):108884.

BACKGROUND : Autism Spectrum Disorder (ASD) is a neurodevelopmental disability with altered connectivity in brain networks. NEW METHOD : In this study, brain connections in Resting-state functional Magnetic Resonance Imaging (Rs-fMRI) of ASD and Typical Developing (TD) are analyzed by partial and full correlation methods such as Gaussian Graphical Least Absolute Shrinkage and Selection Operator (GLASSO), Max-Det Matrix Completion (MDMC), and Pearson Correlation Co-Efficient (PCCE). We investigated Functional Connectivity (FC) of ASD and TD brain from 238 functionally defined regions of interest. Furthermore, we constructed a series of feature sets by applying conditional random forests and conditional permutation importance. We built classifier models by Random Forest (RF), Oblique RF (ORF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN) for each feature set. FC features are ranked based on p-value and we analyzed the top 20 FC features. RESULTS : We achieved a single-trial test accuracy of 72.5%, though MDMC-SVM and PCCE-CNN pipelines. Further, PCCE-CNN pipeline gives better average test accuracy (70.31%) and area under the curve (0.73) compared to other pipelines. We found that top-20 PCCE based FC features are from networks such as Dorsal Attention (DA), Cingulo-Opercular Task Control (COTC), somatosensory motor hand and subcortical. In addition, among top 20 PCCE features, many FC links are found between COTC and DA (4 connections) which helped to discriminate the ASD and TD. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS : The generalized classifier models built in our study for highly heterogeneous participants perform better than previous studies with similar data sets and diagnostic groups.

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9. Friedman C. Social determinants of health, emergency department utilization, and people with intellectual and developmental disabilities. Disabil Health J ;2020 (Jun 24):100964.

BACKGROUND : People with intellectual and developmental disabilities’ (IDD’s) health is largely dependent on the government services they receive. Medicaid managed care has emerged as one mechanism used to provide services to people with disabilities in an attempt to reduce costs. In managed care, there has been an emphasis on reducing emergency department visits and hospital admissions in an effort to reduce expenditures. OBJECTIVE : The purpose of this exploratory study was to examine the impact social determinants of health -"conditions in the environments in which people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks" (n.p.)(1) - had on the emergency department utilization of people with IDD. METHODS : We had the following research question : what is the relationship between social determinants and emergency department utilization (visits) among adults with IDD ? To explore this research question, a negative binomial regression analysis was used with secondary social determinant outcomes data (from Personal Outcome Measures®) and emergency department visit data from a random sample of 251 people with IDD. We also examined relationships with participants’ demographics. RESULTS : Our findings revealed for every one unit increase in the number of social determinant outcomes present, there was a 7.97% decrease in emergency department visits. There were also significant relationships between emergency department visits, and complex support needs, intellectual disability level, primary communication method, and residence type. CONCLUSIONS : Social determinants are critical to promote the quality of life and health equity of people with IDD.

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10. Hillman CB, Lerman DC, Kosel ML. Discrete-trial training performance of behavior interventionists with autism spectrum disorder : A systematic replication and extension. J Appl Behav Anal ;2020 (Jul 31)

Further research is needed on strategies to improve employment outcomes for individuals with autism spectrum disorder (ASD). We replicated and extended prior research by examining the acquisition, maintenance, and generalization of discrete-trial training (DTT) performance of adults with ASD who were interested in careers as behavior technicians. Three participants received training on how to implement DTT with children and we assessed the maintenance and generalization of DTT performance in the absence of feedback. Results indicated that procedural integrity generalized across children and targets and maintained for 6 to 17 session days without feedback. Results have implications for the successful employment of individuals with ASD as behavior technicians and for future research on strategies to enhance their performance on the job.

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11. Kurek M, Borowska B, Lubowiedzka-Gontarek B, Rosset I, Żądzińska E. Disturbances in primary dental enamel in Polish autistic children. Sci Rep ;2020 (Jul 29) ;10(1):12751.

Dental enamel is a structure that is formed as a result of the regular functioning of ameloblasts. The knowledge of the patterns of enamel secretion allows an analysis of their disruptions manifested in pronounced additional accentuated lines. These lines represent a physiological response to stress experienced during enamel development. The aim of this study was to assess the occurrence of accentuated lines in the tooth enamel of autistic boys. The width of the neonatal line and the periodicity of the striae of Retzius were also assessed. The study material consisted of longitudinal ground sections of 56 primary teeth (incisors and molars) : 22 teeth from autistic children and 34 teeth from the control group. The Mann-Whitney U test indicates that the accentuated lines were found significantly more often in autistic children (Z = 3.03 ; p = 0.002). No differentiation in the rate of enamel formation and in the rate of regaining homeostasis after childbirth were found. The obtained results may indicate a higher sensitivity of autistic children to stress factors, manifested in more frequent disturbances in the functioning of ameloblasts or may be a reflection of differences in the occurrence of stress factors in the first years of life in both analyzed groups.

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12. Rathore A, Palande S, Anderson JS, Zielinski BA, Fletcher PT, Wang B. Autism Classification Using Topological Features and Deep Learning : A Cautionary Tale. Med Image Comput Comput Assist Interv ;2019 (Oct) ;11766:736-744.

The identification of autistic individuals using resting state functional connectivity networks can provide an objective diagnostic method for autism spectrum disorder (ASD). The present state-of-the-art machine learning model using deep learning has a classification accuracy of 70.2% on the ABIDE (Autism Brain Imaging Data Exchange) data set. In this paper, we explore the utility of topological features in the classification of ASD versus typically developing control subjects. These topological features have been shown to provide a complementary source of discriminative information in applications such as 2D object classification and social network analysis. We evaluate the performance of three different representations of topological features - persistence diagrams, persistence images, and persistence landscapes - for autism classification using neural networks, support vector machines and random forests. We also propose a hybrid approach of augmenting topological features with functional correlations, which typically outperforms the models that use functional correlations alone. With this approach, even with a simple 3-layer neural network, we are able to achieve a classification accuracy of 69.2% on the ABIDE data set. However, our experiments also show that the improvement due to topological features is not always statistically significant. Therefore, we offer a cautionary tale to the practitioners regarding the limited discriminative power of topological features derived from fMRI data for the classification of autism.

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13. Sprengers JJ, van Andel DM, Zuithoff NP, Keijzer-Veen MG, Schulp AJ, Scheepers FE, Lilien MR, Oranje B, Bruining H. Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI) : A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase Two, Superiority Trial. J Am Acad Child Adolesc Psychiatry ;2020 (Jul 25)

OBJECTIVE : Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). We tested efficacy of bumetanide on core symptom domains using a mono-center, parallel-group, participant-randomized, double-blind, placebo-controlled phase-2 superiority trial in a tertiary Netherlands hospital. METHOD : Unmedicated children aged 7-15 with ASD and IQ>55 were block-randomized 1:1 to oral-solution bumetanide vs. placebo, titrated to a maximum of 1.0mg twice-daily for 91 days (D91) followed by a 28-day wash-out period. The primary outcome was difference in Social Responsiveness Scale-2 (SRS-2) total score at D91 analyzed by modified intention-to-treat with linear mixed models. RESULTS : 92 participants (mean age 10.5 years [SD 2.4]) enrolled between June 2016 and December 2018. 47 children were allocated to bumetanide and 45 to placebo. Two participants dropped out per treatment arm. After 91 days, bumetanide was not superior to placebo on the primary outcome, the SRS-2 (Mean difference -3.16, 95% CI : -9.6823 to 3.3659, p=0.3375). A superior effect was found on one of the secondary outcomes, the Repetitive Behavior Scale-Revised (Mean difference -4.16, 95%CI : -8.0649 to -0.2473, p=0.0375), not on the Sensory Profile (Mean difference 5.64, 95%CI : -11.30 to 22.57, p=0.508) nor the Aberrant Behavior Checklist Irritability Subscale (Mean difference -0.65, 95%CI : -2.83 to 1.52, p=0.552). No significant wash-out effect was observed. Significant adverse effects were predominantly diuretic effects (orthostatic hypotension (17[36%] vs 5[11%], p=.007) ; hypokalemia (24[51%] vs 0[0%], p<0.0001), whose occurrence did not statistically influence treatment outcome. CONCLUSION : The trial was negative as no superior effect was found on the primary outcome. The secondary outcomes might suggest efficacy on repetitive behavior symptoms for a subset of patients.

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14. Stewart SL, Babcock SE, Li Y, Dave HP. A psychometric evaluation of the interRAI Child and Youth Mental Health instruments (ChYMH) anxiety scale in children with and without developmental disabilities. BMC Psychiatry ;2020 (Jul 29) ;20(1):390.

BACKGROUND : With 10 to 20% of Canadian children suffering with mental illness, the importance of early identification and accurate assessment systems is clear. Unfortunately, many do not receive the mental health treatment necessary and wait-times for assessment can span up to a year. In response, the interRAI suite of assessments were designed to comprehensively assess early signs of mental health impairments in children from birth to 18 years. METHODS : This study assesses the psychometric properties of the Anxiety Scale and addresses the identification of anxiety within children diagnosed with intellectual and developmental disabilities (IDD) ; a commonly underrepresented sample in mental health psychometric studies. Data was collected from children aged 4-18 years in three different samples. RESULTS : Results indicated reliable internal consistency and factor structure, as well as moderate-to-strong convergent validity. CONCLUSIONS : We conclude that the Anxiety Scale exhibits psychometric qualities which demonstrate its clinical utility for use within a child sample, as well as in children with IDD. The findings provide support to a larger body of research which show consistent psychometric rigour of the interRAI measures.

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15. Williams CM, Peyre H, Toro R, Beggiato A, Ramus F. Adjusting for allometric scaling in ABIDE I challenges subcortical volume differences in autism spectrum disorder. Hum Brain Mapp ;2020 (Jul 30)

Inconsistencies across studies investigating subcortical correlates of autism spectrum disorder (ASD) may stem from small sample size, sample heterogeneity, and omitting or linearly adjusting for total brain volume (TBV). To properly adjust for TBV, brain allometry-the nonlinear scaling relationship between regional volumes and TBV-was considered when examining subcortical volumetric differences between typically developing (TD) and ASD individuals. Autism Brain Imaging Data Exchange I (ABIDE I ; N = 654) data was analyzed with two methodological approaches : univariate linear mixed effects models and multivariate multiple group confirmatory factor analyses. Analyses were conducted on the entire sample and in subsamples based on age, sex, and full scale intelligence quotient (FSIQ). A similar ABIDE I study was replicated and the impact of different TBV adjustments on neuroanatomical group differences was investigated. No robust subcortical allometric or volumetric group differences were observed in the entire sample across methods. Exploratory analyses suggested that allometric scaling and volume group differences may exist in certain subgroups defined by age, sex, and/or FSIQ. The type of TBV adjustment influenced some reported volumetric and scaling group differences. This study supports the absence of robust volumetric differences between ASD and TD individuals in the investigated volumes when adjusting for brain allometry, expands the literature by finding no group difference in allometric scaling, and further suggests that differing TBV adjustments contribute to the variability of reported neuroanatomical differences in ASD.

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16. Yin J, Cai J, Hu J, Qin C, Li L, Shen D, Tian G, Zou X, Seeberger PH. Chemical Synthesis Elucidates the Key Antigenic Epitope of the Autism-related Bacterium Clostridium bolteae Capsular Octadecasaccharide. Angew Chem Int Ed Engl ;2020 (Jul 31)

The gut pathogen Clostridium bolteae has been associated with the onset of autism spectrum disorder (ASD). To create vaccines against C. bolteae , it is important to identify exact protective epitopes of the immunologically active capsular polysaccharide (CPS). Here, we prepared a series of C. bolteae CPS glycans up to an octadecasaccharide. Key to achieving the total syntheses is a [2+2] coupling strategy based on a β-d-Rha p -(1→3)-α-d-Man p repeating unit that in turn was accessed via a stereoselective β-d-rhamnosylation. The 4,6- O -benzylidene-induced conformational locking is a powerful strategy for forming β-d-mannose-type glycoside. An indirect strategy based on the C2 epimerization of β-d-quinovoside was efficiently achieved by Swern oxidation and borohydride reduction. Sequential glycosylation, regioselective and global deprotection produced disaccharide, tetrasaccharide, all the way to octadecasaccharide. Glycan microarrays analysis of sera from rabbits immunized with inactivated C. bolteae bacteria revealed a humoral immune response to di- and tetrasaccharide but none of the longer sequences. Tetrasaccharide may be a key motif for designing glycoconjugate vaccines against C. bolteae .

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