Pubmed du 26/05/20

mardi 26 mai 2020

1. Bast N, Mason L, Freitag CM, Smith T, Portugal AM, Poustka L, Banaschewski T, Johnson M. Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder. J Child Psychol Psychiatry. 2020.

BACKGROUND : Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. METHODS : Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6-30 years), cognitive ability (60-140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. RESULTS : We observed decreased saccade duration (∆M = -0.50, CI [-0.21, -0.78]) and amplitude (∆M = -0.42, CI [-0.12, -0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. CONCLUSIONS : We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD.

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2. Chen B, Linke A, Olson L, Ibarra C, Reynolds S, Müller RA, Kinnear M, Fishman I. Greater functional connectivity between sensory networks is related to symptom severity in toddlers with autism spectrum disorder. J Child Psychol Psychiatry. 2020.

BACKGROUND : Symptoms of autism spectrum disorder (ASD) emerge in the first years of life. Yet, little is known about the organization and development of functional brain networks in ASD proximally to the symptom onset. Further, the relationship between brain network connectivity and emerging ASD symptoms and overall functioning in early childhood is not well understood. METHODS : Resting-state fMRI data were acquired during natural sleep from 24 young children with ASD and 23 typically developing (TD) children, aged 17-45 months. Intrinsic functional connectivity (iFC) within and between resting-state functional networks was derived with independent component analysis (ICA). RESULTS : Increased iFC between visual and sensorimotor networks was found in young children with ASD compared to TD participants. Within the ASD group, the degree of overconnectivity between visual and sensorimotor networks was associated with greater autism symptoms. Age-related weakening of the visual-auditory between-network connectivity was observed in the ASD but not the TD group. CONCLUSIONS : Taken together, these results provide evidence for disrupted functional network maturation and differentiation, particularly involving visual and sensorimotor networks, during the first years of life in ASD. The observed pattern of greater visual-sensorimotor between-network connectivity associated with poorer clinical outcomes suggests that disruptions in multisensory brain circuitry may play a critical role for early development of behavioral skills and autism symptomatology in young children with ASD.

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3. Dell’Osso L, Lorenzi P, Carpita B. Camouflaging : psychopathological meanings and clinical relevance in autism spectrum conditions. CNS spectrums. 2020 : 1-8.

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4. Frasch MG, Shen C, Wu HT, Mueller A, Neuhaus E, Bernier RA, Kamara D, Beauchaine TP. Brief Report : Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children ?. J Autism Dev Disord. 2020.

Several studies show altered heart rate variability (HRV) in autism spectrum disorder (ASD), but findings are neither universal nor specific to ASD. We apply a set of linear and nonlinear HRV measures-including phase rectified signal averaging-to segments of resting ECG data collected from school-age children with ASD, age-matched typically developing controls, and children with other psychiatric conditions characterized by altered HRV (conduct disorder, depression). We use machine learning to identify time, frequency, and geometric signal-analytical domains that are specific to ASD (receiver operating curve area = 0.89). This is the first study to differentiate children with ASD from other disorders characterized by altered HRV. Despite a small cohort and lack of external validation, results warrant larger prospective studies.

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5. Nadeem R, Hussain T, Sajid H. C reactive protein elevation among children or among mothers’ of children with autism during pregnancy, a review and meta-analysis. BMC Psychiatry. 2020 ; 20(1) : 251.

OBJECTIVE : To evaluate if children with ASD, or mothers of ASD children have elevated CRP during pregnancy. BACKGROUND : Autism spectrum disorder (ASD) is a neuro developmental disorder with incidence of 1 in 68 children occur in all racial, ethnic, and socioeconomic groups. Economic burden between $11.5 billion - $60.9 billion and family average medical expenditures of $4110-$6200 per year. Conflicting evidence exist about role of maternal CRP during pregnancy with ASD child. METHODS : Searches on database ; Pubmed, Medline, Embase and google scholar using key words ; C reactive protein (CRP), Maternal CRP, ASD, autism, autistic disorder, Inflammation. All English-language studies published between 1960 and 2019 pertaining to CRP and ASD. All Studies which provided data on CRP levels during pregnancy (mCRP) of Mothers of offsprings with ASD and (mCRP) of mothers of normal subjects were selected. Data were extracted in the form of odd ratios of having high mCRP in mothers of children with ASD versus mCRP of mothers of normal controls. Since these odd ratios were adjusted, therefore no Meta regression were attempted. Significant heterogeneity was found ; therefore, random effect model was employed. RESULTS : Review of CRP levels in children with ASD showed higher level in children with ASD than control, although different methodology and absence of numerical data did not allow metanalysis. Regarding mCRP and ASD, three studies were identified that provide data on mCRP and ASD. Four datasets were created from these 3 studies as the study by Zerbo et al. provided data in 2 subsets. Total number of subjects were 5258 (Brown, N = 677, Zerbo = 416, Koks = 4165) extracted data from these studies was pooled for analysis. Random effect model was employed and substantial heterogeneity among the studies was observed 11. Mothers of children with ASD have adjusted Odd ratio of 1.02 (0.948 to 1.103, I2 = 75, P = 0.558) to have high mCRP comparing mothers of control. CONCLUSION : Mothers of children with ASD appear not to have elevated CRP during pregnancy. Children with ASD appear to have higher levels of CRP levels.

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6. Nyström P, Jones E, Darki F, Bölte S, Falck-Ytter T. Atypical Topographical Organization of Global Form and Motion Processing in 5-Month-Old Infants at Risk for Autism. J Autism Dev Disord. 2020.

Research indicates that individuals with autism spectrum disorder (ASD) are superior at local processing while the integration of local features to global percepts is reduced. Here, we compared infants at familiar risk for ASD to typically developing infants in terms of global coherence processing at 5 months of age, using steady state visually evoked potentials (SSVEP). We found a different topographical organization for global form and motion processing in infants at risk (n = 50) than in controls (n = 23). In contrast, activation patterns for local visual change were strikingly similar between groups. Although preliminary, the results represent the first neurophysiological evidence supporting the view that basic atypicalities in perception may play a role in the developmental pathways leading to ASD.

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7. Perez BC, Bacotti JK, Peters KP, Vollmer TR. An extension of commonly used toilet-training procedures to children with autism spectrum disorder. Journal of applied behavior analysis. 2020.

The current study evaluated a toilet-training treatment package described by Greer et al. (2016) with children diagnosed with autism spectrum disorder (ASD). Most of the current research on toilet-training interventions for children with ASD are replications and modifications of Azrin and Foxx (1971) or (more recently) LeBlanc et al. (2005). However, these procedures are composed of components that are not included in studies with typically developing (TD) children. For example, Greer et al. evaluated the effectiveness of three typical components within a toilet-training package, mostly with TD participants : a 30-min sit schedule, placing participants in underwear, and differential reinforcement. The primary purpose of the current study was to replicate and extend the treatment package described by Greer et al. to children with ASD. A secondary purpose was to evaluate modifications necessary for individualized toilet training when the commonly used components were ineffective. The results of Greer et al. were replicated for 11 participants with ASD in the current study, suggesting that intensive toileting interventions (e.g., interventions requiring overcorrection, reprimands, and dense sit schedules) may only be necessary for a subset of individuals with ASD.

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8. Price J. Cell therapy approaches to autism : a review of clinical trial data. Mol Autism. 2020 ; 11(1) : 37.

A number of clinical trials of cell therapies for autism spectrum disorder have been conducted, and some have published their outcomes. This review considers the data that have emerged from this small set of published trials, evaluates their success, and proposes further steps that could be taken if this field of endeavour is to be pursued further. A number of reservations arise from this tranche of studies, specifically the absence of identified therapeutic targets, and deficiencies in the therapeutic approach that is being employed. If this therapeutic direction is to be pursued further, then additional pre-clinical studies are recommended that might lead to improvements in patient stratification, biomarkers, the defined mode of action, and the preparation and identification of the therapeutic cells themselves.

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9. Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wang D, Hwang SH, Hammock BD, Hashimoto K. Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase. Proceedings of the National Academy of Sciences of the United States of America. 2020 ; 117(21) : 11753-9.

Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.

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10. Su LD, Xu FX, Wang XT, Cai XY, Shen Y. Cerebellar Dysfunction, Cerebro-cerebellar Connectivity and Autism Spectrum Disorders. Neuroscience. 2020.

The cerebellum has long been conceptualized to control motor learning and motor coordination. However, increasing evidence suggests its roles in cognition and emotion behaviors. In particular, the cerebellum has been recognized as one of key brain regions affected in autism spectrum disorder (ASD). To better understand the contribution of the cerebellum in ASD pathogenesis, we here discuss recent behavioral, genetic, and molecular studies from the human and mouse models. In addition, we raise several questions that need to be investigated in future studies from the point view of cerebellar dysfunction, cerebro-cerebellar connectivity and ASD.

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11. Young S, Hollingdale J, Absoud M, Bolton P, Branney P, Colley W, Craze E, Dave M, Deeley Q, Farrag E, Gudjonsson G, Hill P, Liang HL, Murphy C, Mackintosh P, Murin M, O’Regan F, Ougrin D, Rios P, Stover N, Taylor E, Woodhouse E. Guidance for identification and treatment of individuals with attention deficit/hyperactivity disorder and autism spectrum disorder based upon expert consensus. BMC medicine. 2020 ; 18(1) : 146.

BACKGROUND : Individuals with co-occurring hyperactivity disorder/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) can have complex presentations that may complicate diagnosis and treatment. There are established guidelines with regard to the identification and treatment of ADHD and ASD as independent conditions. However, ADHD and ASD were not formally recognised diagnostically as co-occurring conditions until the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) was published in 2013. Hence, awareness and understanding of both conditions when they co-occur is less established and there is little guidance in the clinical literature. This has led to uncertainty among healthcare practitioners when working with children, young people and adults who present with co-existing ADHD and ASD. The United Kingdom ADHD Partnership (UKAP) therefore convened a meeting of professional experts that aimed to address this gap and reach expert consensus on the topic that will aid healthcare practitioners and allied professionals when working with this complex and vulnerable population. METHOD : UK experts from multiple disciplines in the fields of ADHD and ASD convened in London in December 2017. The meeting provided the opportunity to address the complexities of ADHD and ASD as a co-occurring presentation from different perspectives and included presentations, discussion and group work. The authors considered the clinical challenges of working with this complex group of individuals, producing a consensus for a unified approach when working with male and female, children, adolescents and adults with co-occurring ADHD and ASD. This was written up, circulated and endorsed by all authors. RESULTS : The authors reached a consensus of practical recommendations for working across the lifespan with males and females with ADHD and ASD. Consensus was reached on topics of (1) identification and assessment using rating scales, clinical diagnostic interviews and objective supporting assessments ; outcomes of assessment, including standards of clinical reporting ; (2) non-pharmacological interventions and care management, including psychoeducation, carer interventions/carer training, behavioural/environmental and Cognitive Behavioural Therapy (CBT) approaches ; and multi-agency liaison, including educational interventions, career advice, occupational skills and training, and (3) pharmacological treatments. CONCLUSIONS : The guidance and practice recommendations (Tables 1, 4, 5, 7, 8 and 10) will support healthcare practitioners and allied professionals to meet the needs of this complex group from a multidisciplinary perspective. Further research is needed to enhance our understanding of the diagnosis, treatment and management of individuals presenting with comorbid ADHD and ASD.

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12. Yu X, Wang X, Sakano H, Zorio DAR, Wang Y. Dynamics of the Fragile X Mental Retardation Protein Correlates with Cellular and Synaptic Properties in Primary Auditory Neurons following Afferent Deprivation. J Comp Neurol. 2020.

Afferent activity dynamically regulates neuronal properties and connectivity in the central nervous system. The Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates cellular and synaptic properties in an activity-dependent manner. Whether and how FMRP level and localization are regulated by afferent input remains sparsely examined and how such regulation is associated with neuronal response to changes in sensory input is unknown. We characterized changes in FMRP level and localization in the chicken nucleus magnocellularis (NM), a primary cochlear nucleus, following afferent deprivation by unilateral cochlea removal. We observed rapid (within 2 hours) aggregation of FMRP immunoreactivity into large granular structures in a subset of deafferented NM neurons. Neurons that exhibited persistent FMRP aggregation at 12-24 hours eventually lost cytoplasmic Nissl substance, indicating cell death. A week later, FMRP expression in surviving neurons regained its homeostasis, with a slightly reduced immunostaining intensity and enhanced heterogeneity. Correlation analyses under the homeostatic status (7-14 days) revealed that neurons expressing relatively more FMRP had a higher capability of maintaining cell body size and ribosomal activity, as well as a better ability to detach inactive presynaptic terminals. Additionally, the intensity of an inhibitory postsynaptic protein, gephyrin, was reduced following deafferentation and was positively correlated with FMRP intensity, implicating an involvement of FMRP in synaptic dynamics in response to reduced afferent inputs. Collectively, this study demonstrates that afferent input regulates FMRP expression and localization in ways associated with multiple types of neuronal responses and synaptic rearrangements. This article is protected by copyright. All rights reserved.

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13. Zachor DA, Ben-Itzchak E. From Toddlerhood to Adolescence, Trajectories and Predictors of Outcome : Long-Term Follow-Up Study in Autism Spectrum Disorder. Autism Res. 2020.

This study is one of a very few prospective long-term studies in autism spectrum disorder (ASD). The study compared outcome trajectories in three adolescent groups (T2) : "best outcome" (BO, n = 11) did not meet cut-off points for ASD and IQ scores ≥85 ; high functioning (HF-ASD, n = 14) ; and lower functioning (LF-ASD, n = 43). Additionally, the study searched for characteristics at toddlerhood (T1) that may predict belonging to the above groups. The study included 68 adolescents (63 males) diagnosed with ASD at toddlerhood (mean age : 13:10 years), mean follow-up time was 11:7 years. Participants underwent comprehensive assessments at T1 and T2. Different trajectories were found for the three defined groups. The BO group improved significantly in cognitive ability, autism severity, and adaptive skills in comparison to no improvement for the LF-ASD group or partial progress for the HF-ASD group. At toddlerhood, better cognition and less severe autism social affect symptoms were generally associated with a better outcome. Early social behaviors including better "pointing," "facial expression directed to others," "showing," and "response to joint attention" were associated with membership in the BO group. In addition, the BO group had the lowest prevalence of significant T2 inattention and anxiety symptoms. No significant differences between the three outcome groups were noted in the birth and prevalence of medical problems. Higher cognitive ability and better T1 showing and pointing behaviors predicted better outcome. The study points to the change in autism severity over time and to the prognostic value of early developmental abilities, social engagement behaviors, and the existence of comorbidities. LAY SUMMARY : This long-term study compared characteristics of toddlers diagnosed with autism spectrum disorder (ASD) in three outcome groups in adolescence : best outcome (BO-average IQ/not meeting criteria for ASD), high-functioning ASD, and low-functioning ASD (LF-ASD). At toddlerhood, the BO group displayed less severe autism symptoms, mostly in sharing interests, compared to the LF-ASD group. The BO group had fewer inattention and anxiety symptoms than the two ASD groups. Additionally, early cognitive level and social engagement behaviors predicted outcome in ASD.

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