Pubmed du 07/05/19

mardi 7 mai 2019

1. Akhondzadeh S. Microbiota and Autism Spectrum Disorder. Avicenna journal of medical biotechnology. 2019 ; 11(2) : 129.

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2. Cervantes P, Kuriakose S, Donnelly L, Filton B, Marr M, Okparaeke E, Voorheis K, Havens J, Horwitz S. Sustainability of a Care Pathway for Children and Adolescents with Autism Spectrum Disorder on an Inpatient Psychiatric Service. J Autism Dev Disord. 2019.

Children with autism spectrum disorder (ASD) are frequently hospitalized within general psychiatric settings, which are not usually designed to meet their needs. An initial evaluation of a care pathway developed for youth with ASD receiving services in a general psychiatric inpatient unit (ASD-CP) showed promise in improving outcomes while using few resources (Kuriakose et al. in J Autism Dev Disord 48:4082-4089, 2018). As sustainability of inpatient psychiatric initiatives is imperative but rarely investigated, this study examined the stability of ASD-CP outcomes during an 18-month follow-up period (n = 15) compared to the 18-month initial evaluation (n = 20) and 18-month pre-implementation (n = 17) periods. Decreased use of crisis interventions, including holds/restraints and intramuscular medication use, was sustained in the 18 months after the initial implementation period. Implications and limitations are discussed.

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3. Chandrakumar A, t Jong GW. Maternal Exposure to Air Pollution During Pregnancy and Autism Spectrum Disorder in Offspring. JAMA Pediatr. 2019.

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4. De Vane CL, Charles JM, Abramson RK, Williams JE, Carpenter LA, Raven S, Gwynette F, Stuck CA, Geesey ME, Bradley C, Donovan JL, Hall AG, Sherk ST, Powers NR, Spratt E, Kinsman A, Kruesi MJ, Bragg JE, Jr. Pharmacotherapy of Autism Spectrum Disorder : Results from the Randomized BAART Clinical Trial. Pharmacotherapy. 2019.

STUDY OBJECTIVE : The objective of this trial-Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)-was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. DESIGN : Randomized, double-blind, parallel-group study. SETTING : Three academic medical centers and a single private pediatric practice. PATIENTS : Eighty children or adolescents (aged 6-17 years) with autistic disorder were enrolled, and 61 patients were randomized to study drug. Of those patients, 51 completed the 10-week trial, and 31 completed an optional 12-week blinded extension phase. INTERVENTION : All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed United States Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4 ; patients were then maintained on a fixed dose for 6 additional weeks. MEASUREMENTS AND MAIN RESULTS : Safety, physical, and psychological assessments were recorded weekly or every two weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist irritability subscale after one week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose-limiting adverse events occurred during the dose-titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3-month extension phase (4.36 vs 5.55 kg, p=0.26). CONCLUSION : Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within one week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence-based support for choosing an FDA-approved drug for initial pharmacotherapy for autism spectrum disorder. This article is protected by copyright. All rights reserved.

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5. Frauenberger C, Spiel K, Makhaeva J. Thinking OutsideTheBox - Designing Smart Things with Autistic Children. International journal of human-computer interaction. 2019 ; 35(8) : 666-78.

This article offers a synopsis of and a critical reflection on the research project OutsideTheBox Rethinking Assistive Technology with Autistic Children. The aim of the 3-year project was to develop digital technology that would holistically respond to the complex life-worlds of autistic children, affording positive experiences that they could share with others. Through a series of long-term participatory design processes, smart objects were developed individually with nine children employing a wide range of different methods (e.g., Co-operative Inquiry, Future Workshops, Fictional Inquiry, Magic Workshops, Drama and Making & Digital Fabrication). In this article are presented the cases of all children worked with and tie them together by a critical reflection across them. The discussion offers insights along three main themes : we a) substantiate the argument for a theoretical shift in conceptualizing roles for technology in the lives of disabled people, b) discuss our methodological contributions in participatory design processes and c) propose alternative, participatory approaches to evaluate outcomes.

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6. Gaona C, Castro S, Palikara O. The views and aspirations of young people with autism spectrum disorders and their provision in the new Education Health and Care plans in England. Disabil Rehabil. 2019 : 1-12.

BACKGROUND : The new special educational needs and disability legislation in England has introduced Education Health and Care plans as statutory documents for children with special educational needs, and has extended provision beyond compulsory education, placing transition in a compelling position. This policy recognises the need to include the views, wishes and aspirations of children and young people in the development of provision to cater for their needs. For young people with autism spectrum disorders and their families, transition to post-16 education and employment could be challenging. This study aimed to explore how voices of young people with autism spectrum disorders are captured in their Education Health and Care plans. METHODS : These views were collected from the Education Health and Care plans of 12 young people with autism spectrum disorders. These plans were analysed inductively and deductively through content analysis, using the International Classification of Functioning, Disability and Health : Children and Youth Version as a coding framework. RESULTS : Discrepancies were found between plans concerning the ways in which the voices of young people with ASD were elicited. A total of 189 functioning codes were identified, with a prevalence of activities and participation codes to reflect their views, followed by body functions and lastly environmental factors. CONCLUSION : These disparities are discussed in light of the biopsychosocial model of functioning and health, and the new English policy. Implications for adopting the International Classification of Functioning framework to give voice to young people with autism spectrum disorders are also discussed. Implications for rehabilitation Young people with autism spectrum disorders face many challenges in their transition to post-16 education and employment. Engaging young people with autism spectrum disorders in matters that affect their own lives contribute to the development of provision that is aligned with their wishes and aspirations. Practitioners collaborating in the development of Education Health and Care plans should ensure that young people are effectively involved in the development of their own plans. The International Classification of Functioning, Disability and Health, Children and Youth Version provides a systematic framework and language for coding and recording data from different sources with which to capture young people’s views.

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7. Hutchins NS, Burke MD, Bowman-Perrott L, Tarlow KR, Hatton H. The Effects of Social Skills Interventions for Students With EBD and ASD : A Single-Case Meta-Analysis. Behav Modif. 2019 : 145445519846817.

Social skills interventions are critical for promoting social, emotional, and behavioral competence for students with or at risk of emotional and behavioral disorders (EBD) and autism spectrum disorders (ASD). This single-case meta-analysis examined the effects of social skills interventions (SSIs) for students with EBD and ASD. Effect sizes were calculated for 78 cases across 25 included studies using a nonparametric effect size, Baseline Corrected Tau. The overall weighted mean effect size of 0.54 suggested a moderate effect across the 25 studies. The overall weighted mean effects for studies reporting maintenance and generalization data were 0.68 and 0.37, respectively. Potential moderators examined (disability, intervention design, intervention delivery, methodological quality) were not significant. As such, they did not moderate the outcomes for participants. We conducted a post hoc analysis and hypothesized that between-study differences may be more meaningful than the similarities shared by participants in the same moderator groups. Implications are discussed on using SSIs to address the social, emotional, and behavioral challenges of students with or at risk of EBD and ASD.

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8. Iidaka T, Kogata T, Mano Y, Komeda H. Thalamocortical Hyperconnectivity and Amygdala-Cortical Hypoconnectivity in Male Patients With Autism Spectrum Disorder. Frontiers in psychiatry. 2019 ; 10 : 252.

Background : Analyses of resting-state functional magnetic resonance imaging (rs-fMRI) have been performed to investigate pathophysiological changes in the brains of patients with autism spectrum disorder (ASD) relative to typically developing controls (CTLs). However, the results of these previous studies, which have reported mixed patterns of hypo- and hyperconnectivity, are controversial, likely due to the small sample sizes and limited age range of included participants. Methods : To overcome this issue, we analyzed multisite neuroimaging data from a large sample (n = 626) of male participants aged between 5 and 29 years (mean age = 13 years). The rs-fMRI data were preprocessed using SPM12 and DPARSF software, and signal changes in 90 brain regions were extracted. Multiple linear regression was used to exclude the effect of site differences in connectivity data. Subcortical-cortical connectivity was computed using connectivities in the hippocampus, amygdala, caudate nucleus, putamen, pallidum, and thalamus. Eighty-eight connectivities in each structure were compared between patients with ASD and CTLs using multiple linear regression with group, age, and age x group interactions, head movement parameters, and overall connectivity as variables. Results : After correcting for multiple comparisons, patients in the ASD group exhibited significant increases in connectivity between the thalamus and 19 cortical regions distributed throughout the fronto-parietal lobes, including the temporo-parietal junction and posterior cingulate cortices. In addition, there were significant decreases in connectivity between the amygdala and six cortical regions. The mean effect size of hyperconnectivity (0.25) was greater than that for hypoconnectivity (0.08). No other subcortical structures showed significant group differences. A group-by-age interaction was observed for connectivity between the thalamus and motor-somatosensory areas. Conclusions : These results demonstrate that pathophysiological changes associated with ASD are more likely related to thalamocortical hyperconnectivity than to amygdala-cortical hypoconnectivity. Future studies should examine full sets of clinical and behavioral symptoms in combination with functional connectivity to explore possible biomarkers for ASD.

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9. Missig G, McDougle CJ, Carlezon WA, Jr. Sleep as a translationally-relevant endpoint in studies of autism spectrum disorder (ASD). Neuropsychopharmacology. 2019.

Sleep has numerous advantages for aligning clinical and preclinical (basic neuroscience) studies of neuropsychiatric illness. Sleep has high translational relevance, because the same endpoints can be studied in humans and laboratory animals. In addition, sleep experiments are conducive to continuous data collection over long periods (hours/days/weeks) and can be based on highly objective neurophysiological measures. Here, we provide a translationally-oriented review on what is currently known about sleep in the context of autism spectrum disorder (ASD), including ASD-related conditions, thought to have genetic, environmental, or mixed etiologies. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders. Animal models used in the study of ASD frequently recapitulate dysregulation of sleep and biological (diurnal, circadian) rhythms, suggesting common pathophysiologies across species. As our understanding of the neurobiology of ASD and sleep each become more refined, it is conceivable that sleep-derived metrics may offer more powerful biomarkers of altered neurophysiology in ASD than the behavioral tests currently used in humans or lab animals. As such, the study of sleep in animal models for ASD may enable fundamentally new insights on the condition and represent a basis for strategies that enable the development of more effective therapeutics.

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10. Pagalan L, Brauer M, Lanphear B. Maternal Exposure to Air Pollution During Pregnancy and Autism Spectrum Disorder in Offspring-Reply. JAMA Pediatr. 2019.

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11. Pike G, Lee EE, Khan S. Severe hypernatraemia in a child with autism spectrum disorder. British journal of hospital medicine (London, England : 2005). 2019 ; 80(5) : 292-3.

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12. Russell G, Kapp SK, Elliott D, Elphick C, Gwernan-Jones R, Owens C. Mapping the Autistic Advantage from the Accounts of Adults Diagnosed with Autism : A Qualitative Study. Autism in adulthood : challenges and management. 2019 ; 1(2) : 124-33.

Background : Autism has been associated with specific cognitive strengths. Strengths and weaknesses have traditionally been conceptualized as dichotomous. Methods : We conducted 28 semi-structured interviews with autistic adults. Maximum variation sampling was used to ensure diversity in relation to support needs. We asked which personal traits adults attributed to their autism, and how these have helped in the workplace, in relationships, and beyond. Data were collected in two stages. Responses were analyzed using content and thematic techniques. Results : The ability to hyperfocus, attention to detail, good memory, and creativity were the most frequently described traits. Participants also described specific qualities relating to social interaction, such as honesty, loyalty, and empathy for animals or for other autistic people. In thematic analysis we found that traits associated with autism could be experienced either as advantageous or disadvantageous dependent on moderating influences. Moderating influences included the social context in which behaviors occurred, the ability to control behaviors, and the extent to which traits were expressed. Conclusions : Separating autistic strengths from weaknesses may be a false dichotomy if traits cannot be isolated as separate constructs of strengths or deficits. If attempts to isolate problematic traits from advantageous traits are ill conceived, there may be implications for interventions that have reduction in autistic traits as a primary outcome measure. Lay Summary : Why was this study done ? : The study was done to find out what autistic adults could tell us about their own abilities. They told us about their abilities and how these abilities had helped them in their everyday lives : at work, in their relationships with other people, and at home.What was the purpose of this study ? : To tell a story about what aspects of their autism adults thought were of benefit, when going about their daily lives.What did the researchers do ? : The researchers interviewed 24 adults who had an autism diagnosis. Some lived in residential care and others lived alone in rented apartments. Some people were interviewed twice. Most people said they enjoyed the experience of being interviewed.Once the interviews were done, they were typed up and the researchers tried to figure out what were the common themes over all the stories they had heard. They thought about the themes, then did some more interviews with autistic adults to check they were on the right lines. After discussing them, they wrote the story.What were the results of the study ? : Hyper focus, attention to detail, and the ability to remember were the abilities that autistic people said benefitted them most often. But autistic adults who were interviewed said although their autistic traits were sometimes helpful, at other times they hindered their progress. So the same trait might be useful in some circumstances and unhelpful in other situations. For example, hypersensitivity led one person to enjoy nature, but was difficult to cope with in crowded streets. The study highlights this interchangeability.What do these findings add to what was already known ? : Before, autistic people were known to have both strengths and challenges, but studies tended to separate autistic strengths and weaknesses as different things. We theorize that some traits are expressed as behaviors that may serve to improve or hinder autistic people’s progress, but this depends on their situation (context).What are potential weaknesses in the study ? : Because the researchers used interviews, they did not include any nonverbal autistic people in the study.How will these findings help autistic adults now or in the future ? : It could be useful to think about autism in a way that does not focus on deficits and this study will help us to do that. Plus, if an autistic trait can give people an advantage or a disadvantage, interventions aimed at reducing autistic behaviors might risk dampening advantageous traits as they seek to help with difficulties. That means, autistic adults and children might lose useful abilities when and if they are treated for traits that can also be problematic. The researchers hope their study will lead to more discussion about these types of ideas.

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13. Sedgewick F, Leppanen J, Tchanturia K. Autistic adult outcomes on weight and body mass index : a large-scale online study. Eating and weight disorders : EWD. 2019.

PURPOSE : There has been a wealth of work on the weight outcomes of autistic children and young people, generally finding that they are more likely to be overweight or obese than their non-autistic counterparts. There has not been the same focussed study of the weight outcomes of autistic adults, however. This study, therefore, sought to examine the relationship between weight outcome and being autistic in adults. METHODS : Data were collected as part of an online study looking at eating, autism, and relationships. 665 people gave demographic and mental health information, and group differences and robust regressions were conducted. RESULTS : Autistic adults were more likely to be in non-healthy weight categories than their non-autistic counterparts, i.e., more likely to be underweight, overweight, or obese. There were no interactions between autism status and mental health impacting BMI, although both anxiety and depression predicted higher BMI in the sample overall. CONCLUSIONS : We conclude that while some weight patterns from childhood and adolescence continue into adulthood for autistic individuals, this is not necessarily a straightforward picture, and would benefit from further in-depth and qualitative study to understand the processes at play. The lack of interactions between mental health and autism, however, should provide professionals with confidence in supporting healthy weight management among autistic people. LEVEL OF EVIDENCE : Level III, cohort study.

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14. Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of autism. Neurosci Biobehav Rev. 2019.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse models. Mouse behavioral tests reveal impaired social interaction and communication, as well as increased repetitive behavior and behavioral inflexibility in these mice, which correspond to core behavioral deficits observed in individuals with ASD. However, the connection between these behavioral abnormalities and the underlying dysregulation in neuronal circuits and synaptic function is poorly understood. Moreover, different components of the ASD phenotype may be linked to dysfunction in different brain regions, making it even more challenging to chart the pathophysiological mechanisms involved in ASD. Here we summarize the research on mouse models of ASD and their contribution to understanding pathophysiological mechanisms. Specifically, we emphasize abnormal serotonin production and regulation, as well as the disruption in circadian rhythms and sleep that are observed in a subset of ASD, and propose that spatiotemporal disturbances in brainstem development may be a primary cause of ASD that propagates towards the cerebral cortex.

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15. Tammimies K. Genetic Mechanisms of Regression in Autism Spectrum Disorder. Neurosci Biobehav Rev. 2019.

Developmental regression occurs in approximately one-third of children with autism spectrum disorder (ASD). There is a strong genetic influence in ASD and hundreds of genes have been implicated. Theories suggest that regressive ASD is a neurobiological subtype with potentially different causes. This review examines the evidence of genetic influences in regression and provides a summary of its frequency among ASD-associated single-gene disorders. The few twin- and family studies reporting on the concordance of regressive ASD among twin pairs and siblings provide mixed results, and no conclusions of the variance explained by either genetic or environmental factors can be drawn. Among the 89 genes robustly associated with ASD, 16 have been connected to regression, of which seven showed rates of regression higher than 30% among the mutation carriers. The molecular functions of these genes highlight important roles of transcriptional and synapse regulation for regression. Overall, this review shows our limited understanding of factors influencing regressive ASD and calls for additional studies to answer the open questions.

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16. Thomas RP, Wang LAL, Guthrie W, Cola M, McCleery JP, Pandey J, Schultz RT, Miller JS. What’s in a name ? A preliminary event-related potential study of response to name in preschool children with and without autism spectrum disorder. PLoS One. 2019 ; 14(5) : e0216051.

The ability to selectively respond to one’s own name is important for social and language development, and is disrupted in atypically developing populations (e.g., autism spectrum disorder). Research with typically developing samples using event-related potentials (ERPs) has demonstrated that the subject’s own name (SON) is differentiated from other stimuli at both early sensory and later cognitive stages of auditory processing. While neural indices of response to name have been researched extensively in adults, no such studies have been conducted with typically developing preschool children or children with autism spectrum disorder (ASD). The present study investigated ERP response to name in a sample of typically developing (TD) preschoolers (n = 19 ; mean age = 4.3 years) as well as a small, exploratory comparison group of preschoolers with ASD (n = 13 ; mean age = 4.4 years). TD preschoolers exhibited significantly greater negativity to SON over frontal regions than to an unfamiliar nonsense name, consistent with the adult SON negativity component. This component was present whether the name was spoken by a parent or an unfamiliar adult, suggesting that it reflects SON-specific processing rather than broad self-relevant information processing. Comparing preschoolers with ASD to the TD children revealed a significant SON negativity component across both groups. The amplitude of the SON negativity response was significantly correlated with social variables in the ASD group, though these correlations did not survive correction for multiple comparisons. This study is the first to demonstrate the presence of the SON component in preschool children with and without ASD.

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17. van Sadelhoff JHJ, Perez Pardo P, Wu J, Garssen J, van Bergenhenegouwen J, Hogenkamp A, Hartog A, Kraneveld AD. The Gut-Immune-Brain Axis in Autism Spectrum Disorders ; A Focus on Amino Acids. Frontiers in endocrinology. 2019 ; 10 : 247.

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that affect communication and social behavior. Besides social deficits, systemic inflammation, gastrointestinal immune-related problems, and changes in the gut microbiota composition are characteristic for people with ASD. Animal models showed that these characteristics can induce ASD-associated behavior, suggesting an intimate relationship between the microbiota, gut, immune system and the brain in ASD. Multiple factors can contribute to the development of ASD, but mutations leading to enhanced activation of the mammalian target of rapamycin (mTOR) are reported frequently. Hyperactivation of mTOR leads to deficits in the communication between neurons in the brain and to immune impairments. Hence, mTOR might be a critical factor linking the gut-brain-immune axis in ASD. Pharmacological inhibition of mTOR is shown to improve ASD-associated behavior and immune functions, however, the clinical use is limited due to severe side reactions. Interestingly, studies have shown that mTOR activation can also be modified by nutritional stimuli, in particular by amino acids. Moreover, specific amino acids are demonstrated to inhibit inflammation, improve gut barrier function and to modify the microbiota composition. In this review we will discuss the gut-brain-immune axis in ASD and explore the potential of amino acids as a treatment option for ASD, either via modification of mTOR activity, the immune system or the gut microbiota composition.

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