Pubmed du 28/06/19

vendredi 28 juin 2019

1. Carmassi C, Palagini L, Caruso D, Masci I, Nobili L, Vita A, Dell’Osso L. Systematic Review of Sleep Disturbances and Circadian Sleep Desynchronization in Autism Spectrum Disorder : Toward an Integrative Model of a Self-Reinforcing Loop. Front Psychiatry ;2019 ;10:366.

Background : A compelling number of studies, conducted in both children and adults, have reported an association between sleep disturbances/circadian sleep alterations and autism spectrum disorder (ASD) ; however, the data are sparse and the nature of this link is still unclear. The present review aimed to systematically collect the literature data relevant on sleep disturbances and circadian sleep dysrhythmicity related to ASD across all ages and to provide an integrative theoretical framework of their association. Methods : A systematic review of the MEDLINE, PubMed, and Cochrane databases was conducted from November 2018 to February 2019. The search strategies used were MeSH headings and keywords for "sleep-wake circadian rhythms" OR "circadian sleep disorders" OR "sleep-wake pattern" OR "sleep disorders" OR "melatonin" AND "autism spectrum disorder" OR "autism". Results : One hundred and three studies were identified, 15 regarded circadian sleep dysrhythmicity, 74 regarded sleep disturbances, and 17 regarded melatonin alterations in children and adults with ASD. Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration, low sleep quality/efficiency, and circadian sleep desynchronization such as delayed phases and/or eveningness. Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms. Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD. Conclusions : Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms. These subjects have shown polymorphisms in clock genes expression and in genes involved in melatonin production. The impairment of circadian sleep regulation may increase the individual’s vulnerability to develop symptoms of ASD by altering the sleep regulation in toto, which plays a key role in normal brain development. Even though controversies and "research gaps" are present in literature at this point, we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD. In particular, circadian sleep dysrhythmicity may predispose to develop ASD symptoms and vice versa within a self-reinforcing feedback loop. By targeting sleep disturbances and circadian sleep dysrhythmicity, we may improve treatment strategies for both children and adults with ASD.

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2. D’Croz-Baron DF, Baker M, Michel CM, Karp T. EEG Microstates Analysis in Young Adults With Autism Spectrum Disorder During Resting-State. Front Hum Neurosci ;2019 ;13:173.

Electroencephalography (EEG) is a useful tool to inspect the brain activity in resting state and allows to characterize spontaneous brain activity that is not detected when a subject is cognitively engaged. Moreover, taking advantage of the high time resolution in EEG, it is possible to perform fast topographical reference-free analysis, since different scalp potential fields correspond to changes in the underlying sources within the brain. In this study, the spontaneous EEG resting state (eyes closed) was compared between 10 young adults ages 18-30 years with autism spectrum disorder (ASD) and 13 neurotypical controls. A microstate analysis was applied, focusing on four temporal parameters : mean duration, the frequency of occurrence, the ratio of time coverage, and the global explained variance (GEV). Using data that were acquired from a 65-channel EEG system, six resting-state topographies that best describe the dataset across all subjects were identified by running a two-step cluster analysis labeled as microstate classes A-F. The results indicated that microstates B and E displayed statistically significant differences between both groups among the temporal parameters evaluated. Classes B, D, E, and F were consistently more present in ASD, and class C in controls. The combination of these findings with the putative functional significance of the different classes suggests that during resting state, the ASD group was more focused on visual scene reconstruction, while the control group was more engaged with self-memory retrieval. Furthermore, from a connectivity perspective, the resting-state networks that have been previously associated with each microstate class overlap the brain regions implicated in impaired social communication and repetitive behaviors that characterize ASD.

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3. Giuseppina PM, Giorgia B, Anna G, Claudia C, Sonia C, Francesca B, Alessandra C, Paolo F, Elisabetta M, Patrizia P, Mariangela S. Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder ? Insights from an animal model. Neuropharmacology ;2019 (Jun 24):107686.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by changes in social interactions, impaired language and communication, fear responses and presence of repetitive behaviours. Although the genetic bases of ASD are well documented, the recent increase in clinical cases of idiopathic ASD indicates that several environmental risk factors could play a role in ASD aetiology. Among these, maternal exposure to psychosocial stressors during pregnancy has been hypothesized to affect the risk for ASD in offspring. Here, we tested the hypothesis that preconceptional stressful experiences might also represent crucial elements in the aetiology of ASD. We previously showed that social isolation stress during adolescence results in a marked decrease in the brain and plasma concentrations of progesterone and in the quality of maternal care that these female rats later provide to their young. Here we report that male offspring of socially isolated parents showed decreased agonistic behaviour and social transmission of flavour preference, impairment in reversal learning, increased seizure susceptibility, reduced plasma oxytocin levels, and increased plasma and brain levels of BDNF, all features resembling an ASD-like phenotype. These alterations came with no change in spatial learning, aggression, anxiety and testosterone plasma levels, and were sex-dependent. Altogether, the results suggest that preconceptional stressful experiences should be considered as crucial elements for the aetiology of ASD, and indicate that male offspring of socially isolated parents may be a useful animal model to further study the neurobiological bases of ASD, avoiding the adaptations that may occur in other genetic or pharmacologic experimental models of these disorders.

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4. Heasman B, Gillespie A. Participants Over-Estimate How Helpful They Are in a Two-Player Game Scenario Toward an Artificial Confederate That Discloses a Diagnosis of Autism. Front Psychol ;2019 ;10:1349.

Research on how autistic people are perceived by neurotypical people indicates that disclosing a diagnosis leads to a positive discriminatory bias ; however, autobiographical autistic accounts indicate that diagnostic disclosure often results in negative discriminatory behavior. We report on an exploratory study to compare people’s self-reported helping behavior with their actual helping behavior toward an assumed autistic collaborator. We led 255 participants to believe that they were interacting online with a real person to play Dyad3D, a maze navigation game where players must work together to open doors, and complete the levels. However, participants were actually playing with an artificial confederate (AC) that is programmed to behave the same way across all interactions. This design enabled us to manipulate the diagnostic status of the AC that participants received prior to collaboration across three conditions : no disclosure, dyslexia-disclosure, and autism-disclosure. We use this method to explore two research questions : (1) is Dyad3D viable in creating a simulated interaction that could deceive participants into believing they were collaborating with another human player online ? and (2) what are the effects of disclosing an autism diagnosis on social perception and collaboration ? Combined with a post-game questionnaire, we compared differences between diagnostic conditions and differences between self-reported behavior and actual behavior in the game. Our findings show that Dyad3D proved to be an efficient and viable method for creating a believable interaction (deception success rate >96%). Moreover, diagnostic disclosure of autism results in the AC being perceived as more intelligent and useful, but participants also perceived themselves to be more helpful toward the AC than they actually were. We evaluate the strengths and limitations of the current method and provide recommendations for future research. The source code for Dyad3D is freely available (CC-BY-NC 4.0) so that the study is reproducible and open to future adaptation.

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5. Hooker JL, Dow D, Morgan L, Schatschneider C, Wetherby AM. Psychometric analysis of the repetitive behavior scale-revised using confirmatory factor analysis in children with autism. Autism Res ;2019 (Jun 27)

Research examining restricted and repetitive patterns of behavior or interests (RRB) in autism spectrum disorder (ASD) has increased our understanding of its contribution to diagnosis and its role in development. Advances in our knowledge of RRB are hindered by the inconsistencies in how RRB is measured. The present study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. Confirmatory factor analysis designed for items with categorical response types was implemented to examine six proposed structural models. The five-factor model demonstrated the most parsimonious fit based on common overall fit indices that was further supported by examination of local model fit indicators, though, the four- and six-factor models evidenced adequate-to-good fit as well. Examination of RRB factor score approaches indicated only minor differences between summed item subscale scores and extracted factor scores with regard to associations with diagnostic measures. All RRB subtypes demonstrated significant associations with cognitive functioning and adaptive behavior. Implications for future research validating the RBS-R as a more extensive clinical measure of RRB in ASD are discussed. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Repetitive behaviors are one of the two main symptoms of autism spectrum disorder (ASD). To better understand the role of repetitive behaviors, we must establish effective ways of measuring them. This study assessed the measurement qualities of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. We found that the RBS-R measures multiple types of repetitive behaviors and that these behaviors are related to thinking ability and independence.

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6. Lindor ER, van Boxtel JJA, Rinehart NJ, Fielding J. Motor difficulties are associated with impaired perception of interactive human movement in autism spectrum disorder : A pilot study. J Clin Exp Neuropsychol ;2019 (Jun 26):1-19.

Introduction : The ability to accurately perceive human movement is fundamental to social functioning and known to be influenced by one’s own motor skills. In Autism Spectrum Disorder (ASD), there is ongoing debate about whether human movement perception is impaired. Given that motor skills vary considerably among these individuals, it may be that human movement perception is differentially affected as a function of motor proficiency. The aim of the current study was, thus, to explore whether individuals with ASD with and without motor difficulties differ in the way they visually attend to and perceive human movement. Method : Three groups of children aged 6 to 14 completed the study : an ASD group with motor difficulties (ASDMD), an ASD group without motor difficulties (ASDNMD), and a typically-developing control group (TD). All participants (N = 31) underwent eye-tracking while they viewed communicative interactions performed by two point-light actors. Primary analyses considered group differences in perceptual accuracy and gaze patterns. Results : Results revealed poorer perceptual accuracy in the ASDMD group compared to the ASDNMD and TD groups. Both ASD groups also exhibited gaze anomalies. Unlike the ASDNMD and TD groups who preferentially allocated their gaze to the actor initiating the interaction, the ASDMD group gazed at both actors equally. In contrast, the ASDNMD group shifted their gaze between the actors more frequently than the other groups. Conclusions : These preliminary findings suggest that individuals with ASD and co-occurring motor difficulties employ an atypical attentional style that may hinder accurate human movement perception, whereas those without motor difficulties may employ a compensatory attentional style that facilitates typical perception. Improving our understanding of how attention and perception are affected across the ASD spectrum has the potential to provide insight into the mechanisms that underlie the core social deficits that define this disorder.

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7. Maussion G, Rocha C, Bernard G, Beitel LK, Durcan TM. Patient-Derived Stem Cells, Another in vitro Model, or the Missing Link Toward Novel Therapies for Autism Spectrum Disorders ?. Front Pediatr ;2019 ;7:225.

Autism Spectrum Disorders (ASDs) is a multigenic and multifactorial neurodevelopmental group of disorders diagnosed in early childhood, leading to deficits in social interaction, verbal and non-verbal communication and characterized by restricted and repetitive behaviors and interests. To date, genetic, descriptive and mechanistic aspects of the ASDs have been investigated using mouse models and post-mortem brain tissue. More recently, the technology to generate stem cells from patients’ samples has brought a new avenue for modeling ASD through 2D and 3D neuronal models that are derived from a patient’s own cells, with the goal of building new therapeutic strategies for treating ASDs. This review analyses how studies performed on mouse models and human samples can complement each other, advancing our current knowledge into the pathophysiology of the ASDs. Regardless of the genetic and phenotypic heterogeneities of ASDs, convergent information regarding the molecular and cellular mechanisms involved in these disorders can be extracted from these models. Thus, considering the complexities of these disorders, patient-derived models have immense potential to elucidate molecular deregulations that contributed to the different autistic phenotypes. Through these direct investigations with the human in vitro models, they offer the potential for opening new therapeutic avenues that can be translated into the clinic.

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8. Shefer S, Leon Attia O, Rosenan R, Wald OA, Ende H, Gabis LV. Benefits of medical clowning in the treatment of young children with autism spectrum disorder. Eur J Pediatr ;2019 (Jun 26)

We investigated the contribution of group therapy delivered by a medical clown to young children diagnosed with autism spectrum disorder (ASD). So far, scientific publications regarding medical clowning focus on general health advantages. The current study is the first controlled research examining the use of medical clowning in the therapy for children with ASD. Twenty-four children aged 2-6 years old with ASD enrolled in our special education intensive program were examined before and after group sessions with clown intervention (CI) and other intervention (OI). We tested stereotypic behaviors, verbal expression, play reciprocity, and social smiles. Data was collected during 12 weeks of intervention, and the trajectory of change was evaluated in addition to the pre-/post-intervention.Conclusion : improvement over time in all measures : Significant increase in word production, play reciprocity, and amount of social smiles during CI as compared with OI. We also found a reduction in frequency of stereotypic behaviors during and following CI as compared with before CI. These preliminary results indicate that medical clowning may be beneficial for young children with ASD, since it promotes communication and social reciprocity in a fun and lively interventional setting. What is Known : * Many therapies are used and proven as efficacious interventions for children with ASD. * So far, medical clowning was not tested as an intervention or therapy for ASD. What is New : * Medical clowning sessions with children with ASD elicited enhanced communication during the interventions as compared with other interventions. * Medical clowning sessions contributed to a decrease in frequency of stereotypic movements over time, in children with ASD.

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9. Verma V, Paul A, Amrapali Vishwanath A, Vaidya B, Clement JP. Understanding intellectual disability and autism spectrum disorders from common mouse models : synapses to behaviour. Open Biol ;2019 (Jun 28) ;9(6):180265.

Normal brain development is highly dependent on the timely coordinated actions of genetic and environmental processes, and an aberration can lead to neurodevelopmental disorders (NDDs). Intellectual disability (ID) and autism spectrum disorders (ASDs) are a group of co-occurring NDDs that affect between 3% and 5% of the world population, thus presenting a great challenge to society. This problem calls for the need to understand the pathobiology of these disorders and to design new therapeutic strategies. One approach towards this has been the development of multiple analogous mouse models. This review discusses studies conducted in the mouse models of five major monogenic causes of ID and ASDs : Fmr1, Syngap1, Mecp2, Shank2/3 and Neuroligins/Neurnexins. These studies reveal that, despite having a diverse molecular origin, the effects of these mutations converge onto similar or related aetiological pathways, consequently giving rise to the typical phenotype of cognitive, social and emotional deficits that are characteristic of ID and ASDs. This convergence, therefore, highlights common pathological nodes that can be targeted for therapy. Other than conventional therapeutic strategies such as non-pharmacological corrective methods and symptomatic alleviation, multiple studies in mouse models have successfully proved the possibility of pharmacological and genetic therapy enabling functional recovery.

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10. You YH, Qin ZQ, Zhang HL, Yuan ZH, Yu X. MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR. Biosci Rep ;2019 (Jun 28) ;39(6)

Autism is known as a severe neurobehavioral syndrome, with males affected more often than females. Previous studies have revealed that microRNAs (miRNAs) play a critical role in the search for novel therapeutic strategies for autism. Therefore, we evaluate the ability of miR-153 to influence brain-derived neurotrophic factor (BDNF) of autism as well as proliferation and apoptosis of hippocampal neuron through the janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway by targeting leptin receptor (LEPR). Firstly, the autistic mice models were established and Morris water maze was employed for the analysis of the learning ability and memory of the mice. Besides, in vitro experiments were conducted with the transfection of different mimic, inhibitor, or siRNA into the hippocampal neuron cells, after which the effect of miR-153 on LEPR and the JAK-STAT signaling pathway-related factors was investigated. Next, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and flow cytometry assay were conducted to evaluate cell proliferation, cell cycle, and apoptosis respectively following transfection. The results revealed that there was a significant decrease in learning ability and memory in the autistic mice along with a reduction in the positive expression rate of BDNF and serious inflammatory reaction. LEPR was confirmed as a target gene of miR-153 by the dual luciferase reporter gene assay. After transfection of overexpressed miR-153, LEPR and the JAK-STAT signaling pathway were inhibited followed by an increase in BDNF and enhancement of cell proliferation. In conclusion, the high expression of miR-153 can inhibit activation of JAK-STAT signaling pathway by LEPR, thus improving BDNF expression and the proliferative ability of hippocampal neurons.

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