1. Akers JS, Higbee TS, Gerencser KR, Pellegrino AJ. {{An evaluation of group activity schedules to promote social play in children with autism}}. {J Appl Behav Anal};2018 (May 14)
Children with autism spectrum disorder (ASD) often have deficits in social skills and may avoid engaging in play activities with typically developing peers. The purpose of this study was to identify the utility of activity schedules, with embedded scripts, to teach three children with ASD to play a complex social game. Specifically, children with ASD were taught to play hide-and-seek with typically developing peers. Once the activity schedules were introduced, participants began engaging in independent hide-and-seek behaviors. A secondary purpose of this study was to systematically fade the activity schedules to the least intrusive version. We faded all of the scripts and the majority of activity schedule components for the three participants. Participants continued to play hide-and-seek with the faded versions of the schedules in a novel environment and 2 weeks after treatment concluded.
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2. Al Maskari TS, Melville CA, Willis DS. {{Systematic review: cultural adaptation and feasibility of screening for autism in non-English speaking countries}}. {Int J Ment Health Syst};2018;12:22.
Background: Screening children for autism has gained wider acceptance within clinical practice, and early intervention has improved outcomes. Increasingly, adapting an existing screening instrument is a common, fast method to create a usable screening tool, especially for countries with limited resources and/or expertise. However, concerns have been raised regarding adaptation adequacy and the feasibility of screening across cultural groups. This study systematically examined the levels of cultural adaptation and feasibility aspects considered when screening for autism in non-English speaking countries to build upon the sparse knowledge that exists on this topic in the literature. Methods: Nineteen studies, obtained from five electronic databases, were examined. PRISMA guidance was used for this review. The Ecological Validity Framework model, and Bowen Recommendations for Feasibility were adopted to extract relevant data, which was synthesised narratively. Results: Cultural adaptation within the included studies mostly involved language translation with little information offered to enable conclusions on how the processes were guided and maintained. Few cultural adjustments involved modifying screening methods; clarifying difficult concepts and changing instrument content were employed to address the core values, competence, beliefs, and norms of the adapted culture. However, less attention was given to adapt the screening goals within the context of cultural values, and customs or to consider interactional match between the clients and assessors. The review also highlighted an acceptable level of practicality to screen for autism but did not encourage integrating autism screening within routine practice or beyond the study context for different cultures. Conclusion: Concurring with previous literature, we agree that knowledge on cultural adaptation for autism screening instruments is limited and not sufficiently documented to establish adaptation levels (process and/or contents), and prove adequacy. However, this review provides an infrastructure to improve future adaptation processes. Integrating autism screening as routine medical practice is not encouraged and warrants further feasibility studies to minimize wasted resources and improve screening effectiveness in various health care systems.
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3. Al Sagheer T, Haida O, Balbous A, Francheteau M, Matas E, Fernagut PO, Jaber M. {{Motor impairments correlate with social deficits and restricted neuronal loss in an environmental model of autism}}. {Int J Neuropsychopharmacol};2018 (May 12)
Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders (ASD) but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods: Here, we aimed at determining whether a well-acknowledged animal model of ASD, the valproic acid (VPA) model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received VPA (450 mg/kg) at E12.5 and offspring underwent a battery of behavioral analyses before being sacrificed for histological correlates in motor cortex, nigrostriatal pathway and cerebellum. Results: We show that while VPA male mice show both social and motor impairments, female mice only show motor impairments. Prenatal VPA exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area. Conclusions: Our results suggest that motor dysfunction could contribute to social and communication deficits in ASD and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in ASD may potentially help the quantitative diagnosis of ASD and strategies aimed at improving motor behavior may provide a global therapeutic benefit.
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4. Bennabi M, Gaman A, Delorme R, Boukouaci W, Manier C, Scheid I, Si Mohammed N, Bengoufa D, Charron D, Krishnamoorthy R, Leboyer M, Tamouza R. {{HLA-class II haplotypes and Autism Spectrum Disorders}}. {Sci Rep};2018 (May 16);8(1):7639.
Infections and autoimmunity are associated with autism spectrum disorders (ASD), with both strongly influenced by the genetic regulation of the human leukocyte antigen (HLA) system. The relationship between ASD and the HLA genetic diversity requires further investigation. Using a case control design, the distribution of HLA class II-DRB1 and DQB1 alleles, genotypes and haplotypes were investigated in ASD patients, versus healthy controls (HC). ASD patients meeting DSM-IV TR criteria and HC (474 and 350 respectively) were genotyped at medium resolution using a Luminex-based SSO technology. Comparisons of genotypes, allele frequencies associated with a haplotype analysis were performed. Results indicate: (i) the HLA-DRB1 *11-DQB1*07 haplotype was more prevalent in ASD patients, versus HC (Pc = 0.001), partially replicating previous data and possibly linking to gastro-intestinal (GI)-related pro-inflammatory processes, given that this haplotype associates with pediatric celiac disorders; (ii) the HLA-DRB1 *17-DQB1*02 haplotype was higher in HC, versus ASD patients (Pc = 0.002), indicating that this is a protective haplotype. Using the Autism Diagnostic Interview to assess clinical dimensions, higher scores on social (Pc = 0.006) and non-verbal functioning (Pc = 0.004) associated with the DRB1 *11 DQB1*07 haplotype. Our results support HLA involvement in ASD, with possible relevance to GI and gut-brain axis dysregulation.
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5. Bischof NL, Rapee RM, Hudry K, Bayer JK. {{Acceptability and caregiver-reported outcomes for young children with autism spectrum disorder whose parents attended a preventative population-based intervention for anxiety: A pilot study}}. {Autism Res};2018 (May 15)
This pilot study explored acceptability to parents and outcomes for children of a preventive intervention for anxiety problems in pre-schoolers with autism spectrum disorder (ASD) who were an identified sub-group within a population-based randomised trial of the Cool Little Kids parenting group programme. The population trial included 545 temperamentally inhibited pre-schoolers recruited across eight economically diverse areas of Melbourne, Australia. Within this sample, 26 parents reported that their child had received an ASD diagnosis. Trial measures included baseline inhibited temperament and developmental problems, post-intervention feedback on the programme, and caregiver-reported child mental health outcomes (anxiety diagnoses and internalising symptoms) at 1- and 2-year follow-up. Sample retention for the children with ASD over 2 years was strong (92%). At follow-up, fewer intervention than control children with ASD had anxiety disorders after 1 year (% (n): 25 (3) vs. 77 (10), P = .028) and separation anxiety symptoms after 2 years (M (SD): 4.22 (2.68) vs. 9.38 (5.91), P = .017). Similar effects favouring the intervention group were apparent across other child emotional outcome measures but without statistical significance in this small sample. Parents of the children with ASD reported that Cool Little Kids was « quite useful » in relation to their child’s anxiety but also gave feedback that they would appreciate some tailoring of programme content to the context of ASD. These pilot findings suggest Cool Little Kids may be helpful for reducing comorbid anxiety in pre-schoolers with ASD. Further research is warranted to develop an ASD-specific adaptation which can be trialled with a larger sample of children with confirmed ASD diagnosis. Trial registration ISRCTN30996662 http://www.isrctn.com/ISRCTN30996662. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Many children with autism spectrum disorder (ASD) also have anxiety. This pilot study explored acceptability to parents and outcomes for pre-schoolers with ASD of a parenting group programme to prevent anxiety problems. Among the sample of 26 pre-schoolers with ASD, we found reduced anxiety disorders and separation symptoms when their parents had received the intervention, as reported by caregivers in checklists and clinical interviews. Parents gave feedback that the programme was useful but suggested content be adapted to the context of ASD.
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6. Chan JYS, Lelakowski J, Murgatroyd FD, Boersma LV, Cao J, Nikolski V, Wouters G, Hall MCS. {{Novel Extravascular Defibrillation Configuration With a Coil in the Substernal Space: The ASD Clinical Study}}. {JACC Clin Electrophysiol};2017 (Aug);3(8):905-910.
OBJECTIVES: This study assessed the defibrillation efficacy of the substernal-lateral electrode configuration. BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (ICDs) are regarded as alternatives to transvenous ICDs in certain subjects. However, substantially higher shock energy of up to 80 J may be required. Proposed is a new defibrillation method of placing the shock coil into the substernal space. METHODS: This prospective, nonrandomized, feasibility study was conducted in subjects scheduled for midline sternotomy or implant of ICD. A blunted end tunneling tool was used to insert a defibrillation lead behind the sternum using a percutaneous subxiphoid approach. A skin patch electrode was placed on the left mid-axillary line at the fourth to fifth intercostal space. After ventricular fibrillation induction, a single 35-J shock was delivered between the lead and skin patch. RESULTS: Sixteen subjects (12 males, 4 females; mean age: 61.6 +/- 11.8 years) were enrolled. The mean lead placement time was 11.1 +/- 6.6 min. Of the 14 subjects with successfully induced ventricular fibrillation episodes, 13 subjects (92.9%) had successful defibrillation. The 1 failure was associated with high and lateral shock coil placement. Mean ventricular fibrillation duration was 18.4 +/- 5.6 s with a shock impedance of 98.1 +/- 19.3 ohms. Of the 11 subjects with coil-patch electrograms, the average R-wave amplitude during sinus rhythm was 3.0 +/- 1.4 mV. CONCLUSIONS: These preliminary data demonstrate that substernal defibrillation is feasible and successful defibrillation can be achieved with the shock energy available in current transvenous ICDs. This may open new alternatives to extravascular ICD therapy.
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7. Coffey JM, Vadas A, Puleo Y, Lewis K, Pirone G, Rudolph HL, Helms E, Wood TD, Flynn-Charlebois A. {{Synthesis and Characterization of a deuterium labeled Stercobilin: A Potential Biomarker for Autism}}. {J Labelled Comp Radiopharm};2018 (May 14)
Stercobilin is an end-stage metabolite of hemoglobin, a component of red blood cells. It has been found that there is a significantly lower concentration of stercobilin in the urine of people diagnosed with Autism Spectrum Disorders (ASD), suggesting potential utility as a biomarker. In vitro, we have synthesized stercobilin from its precursor bilirubin through a reduction reaction proceeded by an oxidation reaction. In addition, we have isotopically labeled the stercobilin product with deuterium using this protocol. Nuclear Magnetic Resonance (NMR) investigations show the products of the unlabeled stercobilin (Rxn 1) and the deuterated stercobilin (Rxn 2) both had a loss of signals in the 5.0-7.0 ppm range indicating proper conversion to stercobilin. Changes in the multiplicity of the sp3 region of the proton NMR suggest proper deuterium incorporation. Mass Spectrometry (MS) studies of Rxn 1 show a difference in fragmentation patterns than that of Rxn 2 proposing potential locations for deuterium incorporation. This isotopologue of stercobilin is stable (> 6 months), and further analysis permits investigation for its use as a biomarker and potential quantitative diagnostic probe for ASD.
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8. Deutsch SI, Raffaele CT. {{Understanding facial expressivity in autism spectrum disorder: An inside out review of the biological basis and clinical implications}}. {Prog Neuropsychopharmacol Biol Psychiatry};2018 (May 16)
Deficits in decoding and understanding facially expressed emotions occur commonly in persons with autism spectrum disorder (ASD), which contribute to the impairment of social communication that serves as one of its core diagnostic criteria. Research suggests that abnormalities of visual scanning of the face, activation of key nodes within the « social brain » by facially expressed emotions, functional connectivity within and between nodes of the « social brain », and transduction of specific neurotransmitter/neuromodulatory signals contribute to the pathogenesis of these deficits in at least some persons with ASD. Importantly, the etiologies of these deficits are heterogeneous and include genetic, immunologic, and inflammatory mechanisms, as well as in utero exposures to drugs and toxins. The manifestation and severity of these deficits can also be influenced by developmental age, IQ and genetic background. Consistent with the goals of the Special Issue, the current Review is intended to familiarize the readership with several of the leading neurobiological mechanisms proposed to underlie these deficits in decoding facially expressed emotions and stimulate interest in translational preclinical and clinical investigations, whose ultimate purpose is to attenuate their severity and, thereby, improve functional outcomes of persons with ASD.
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9. Dong D, Zielke HR, Yeh D, Yang P. {{Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder}}. {Autism Res};2018 (May 15)
The molecular pathogenesis of autism spectrum disorder, a neurodevelopmental disorder, is still elusive. In this study, we investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. This study compared the activation of ER stress signals (protein kinase R-like endoplasmic reticulum kinase [PERK], activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 alpha [IRE1alpha]) in different brain regions (prefrontal cortex, hippocampus, cerebellum) in subjects with autism and in age-matched controls. Our data showed that the activation of three signals of ER stress varies in different regions of the autistic brain. IRE1alpha was activated in cerebellum and prefrontal cortex but ATF6 was activated in hippocampus. PERK was not activated in the three regions. Furthermore, the activation of ER stress was confirmed because the expression of C/EBP-homologous protein (CHOP), which is the common downstream indicators of ER stress signals, and most of ER chaperones were upregulated in the three regions. Consistent with the induction of ER stress, apoptosis was found in the three regions by detecting the cleavage of caspase 8 and poly(ADP-ribose) polymerase as well as using the transferase dUTP nick end labeling assay. Moreover, our data showed that oxidative stress was responsible for ER stress and apoptosis because the levels of 4-Hydroxynonenal and nitrotyrosine-modified proteins were significantly increased in the three regions. In conclusion, these data indicate that cellular stress and apoptosis may play important roles in the pathogenesis of autism. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism results in significant morbidity and mortality in children. The functional and molecular changes in the autistic brains are unclear. The present study utilized autistic brain tissues from the National Institute of Child Health and Human Development’s Brain Tissue Bank for the analysis of cellular and molecular changes in autistic brains. Three key brain regions, the hippocampus, the cerebellum, and the frontal cortex, in six cases of autistic brains and six cases of non-autistic brains from 6 to 16 years old deceased children, were analyzed. The current study investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. The activation of three signals of ER stress (protein kinase R-like endoplasmic reticulum kinase, activating transcription factor 6, inositol-requiring enzyme 1 alpha) varies in different regions. The occurrence of ER stress leads to apoptosis in autistic brains. ER stress may result from oxidative stress because of elevated levels of the oxidative stress markers: 4-Hydroxynonenal and nitrotyrosine-modified proteins in autistic brains. These findings suggest that cellular stress and apoptosis may contribute to the autistic phenotype. Pharmaceuticals and/or dietary supplements, which can alleviate ER stress, oxidative stress and apoptosis, may be effective in ameliorating adverse phenotypes associated with autism.
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10. Franchini M, Duku E, Armstrong V, Brian J, Bryson SE, Garon N, Roberts W, Roncadin C, Zwaigenbaum L, Smith IM. {{Variability in Verbal and Nonverbal Communication in Infants at Risk for Autism Spectrum Disorder: Predictors and Outcomes}}. {J Autism Dev Disord};2018 (May 16)
Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.
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11. Guler GD, Rosenwaks Z, Gerhardt J. {{Human DNA Helicase B as a Candidate for Unwinding Secondary CGG Repeat Structures at the Fragile X Mental Retardation Gene}}. {Front Mol Neurosci};2018;11:138.
The fragile X syndrome (FXS) is caused by a CGG repeat expansion at the fragile X mental retardation (FMR1) gene. FMR1 alleles with more than 200 CGG repeats bear chromosomal fragility when cells experience folate deficiency. CGG repeats were reported to be able to form secondary structures, such as hairpins, in vitro. When such secondary structures are formed, repeats can lead to replication fork stalling even in the absence of any additional perturbation. Indeed, it was recently shown that the replication forks stall at the endogenous FMR1 locus in unaffected and FXS cells, suggesting the formation of secondary repeat structures at the FMR1 gene in vivo. If not dealt with properly replication fork stalling can lead to polymerase slippage and repeat expansion as well as fragile site expression. Despite the presence of repeat structures at the FMR1 locus, chromosomal fragility is only expressed under replicative stress suggesting the existence of potential molecular mechanisms that help the replication fork progress through these repeat regions. DNA helicases are known to aid replication forks progress through repetitive DNA sequences. Yet, the identity of the DNA helicase(s) responsible for unwinding the CGG repeats at FMR1 locus is not known. We found that the human DNA helicase B (HDHB) may provide an answer for this question. We used chromatin-immunoprecipitation assay to study the FMR1 region and common fragile sites (CFS), and asked whether HDHB localizes at replication forks stalled at repetitive regions even in unperturbed cells. HDHB was strongly enriched in S-phase at the repetitive DNA at CFS and FMR1 gene but not in the flanking regions. Taken together, these results suggest that HDHB functions in preventing or repairing stalled replication forks that arise in repeat-rich regions even in unperturbed cells. Furthermore, we discuss the importance and potential role of HDHB and other helicases in the resolution of secondary CGG repeat structures.
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12. Kohli JS, Kinnear MK, Fong CH, Fishman I, Carper RA, Muller RA. {{Local Cortical Gyrification is Increased in Children With Autism Spectrum Disorders, but Decreases Rapidly in Adolescents}}. {Cereb Cortex};2018 (May 16)
Extensive MRI evidence indicates early brain overgrowth in autism spectrum disorders (ASDs). Local gyrification may reflect the distribution and timing of aberrant cortical expansion in ASDs. We examined MRI data from (Study 1) 64 individuals with ASD and 64 typically developing (TD) controls (7-19 years), and from (Study 2) an independent sample from the Autism Brain Imaging Data Exchange (n = 31/group). Local Gyrification Index (lGI), cortical thickness (CT), and surface area (SA) were measured. In Study 1, differences in lGI (ASD > TD) were found in left parietal and temporal and right frontal and temporal regions. lGI decreased bilaterally with age, but more steeply in ASD in left precentral, right lateral occipital, and middle frontal clusters. CT differed between groups in right perisylvian cortex (TD > ASD), but no differences were found for SA. Partial correlations between lGI and CT were generally negative, but associations were weaker in ASD in several clusters. Study 2 results were consistent, though less extensive. Altered gyrification may reflect unique information about the trajectory of cortical development in ASDs. While early overgrowth tends to be undetectable in later childhood in ASDs, findings may indicate that a trace of this developmental abnormality could remain in a disorder-specific pattern of gyrification.
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13. Lee KY, Jewett KA, Chung HJ, Tsai NP. {{Loss of Fragile X Protein FMRP Impairs Homeostatic Synaptic Downscaling through Tumor Suppressor p53 and Ubiquitin E3 Ligase Nedd4-2}}. {Hum Mol Genet};2018 (May 16)
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS). We found that the impaired homeostatic synaptic downscaling in Fmr1 KO neurons is caused by loss-of-function dephosphorylation of an epilepsy-associated ubiquitin E3 ligase, neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2. Such dephosphorylation of Nedd4-2 is surprisingly caused by abnormally stable tumor suppressor p53 and subsequently destabilized kinase Akt. Dephosphorylated Nedd4-2 fails to elicit 14-3-3-dependent ubiquitination and down-regulation of the GluA1 subunit of AMPA receptor, and therefore impairs synaptic downscaling. Most importantly, using a pharmacological inhibitor of p53, Nedd4-2 phosphorylation, GluA1 ubiquitination and synaptic downscaling are all restored in Fmr1 KO neurons. Together, our results discover a novel cellular mechanism underlying synaptic downscaling, and demonstrate the dysregulation and successful restoration of this mechanism in the FXS mouse model.
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14. Levy J, Grotto S, Mignot C, Dupont C, Delahaye A, Benzacken B, Keren B, Haye D, Xavier J, Heulin M, Charles E, Verloes A, Maruani A, Pipiras E, Tabet AC. {{NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder}}. {Clin Genet};2018 (May 16)
NR4A2, a member of the nuclear receptor superfamily, is involved in modulation of target gene transcription, regulating several developmental processes such as regulation of cellular homeostasis, neuronal development, inflammation and carcinogenesis. 2q24.1 deletions are extremely rare and only one patient with a de novo deletion encompassing only NR4A2 gene was reported so far. We report three additional patients with a de novo deletion encompassing NR4A2: two patients have deletions encompassing only NR4A2 gene and one patient has a deletion including NR4A2 and the first exon of GPD2. Our patients presented a neurodevelopmental disorder including language impairment, developmental delay, intellectual disability and/or autism spectrum disorder. We suggest that NR4A2 haploinsufficiency is implicated in neurodevelopmental disorder with high penetrance. This article is protected by copyright. All rights reserved.
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15. Ma K, Qin L, Matas E, Duffney LJ, Liu A, Yan Z. {{Histone deacetylase inhibitor MS-275 restores social and synaptic function in a Shank3-deficient mouse model of autism}}. {Neuropsychopharmacology};2018 (Apr 19)
Autism is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Genetic screening has identified synaptic, transcriptional, and chromatin genes disrupted in autistic patients. Haploinsufficiency of Shank3, which encodes a scaffold protein at glutamatergic synapses, is causally linked to autism. Using a Shank3-deficient mouse model that exhibits prominent autism-like phenotypes, we have found that histone acetylation in the prefrontal cortex (PFC) is abnormally low, which can be reversed by MS-275 (also known as Entinostat, SNDX-275), a class I histone deacetylase (HDAC) inhibitor that is selectively potent in PFC. A brief (3-day) treatment with MS-275 (i.p.) led to the sustained (11 days) rescue of autistic social preference deficits in Shank3-deficient mice, without altering locomotion, motor coordination, anxiety, or the increased grooming. MS-275 treatment also rescued the diminished NMDAR surface expression and NMDAR function induced by Shank3 deficiency. Moreover, F-actin at synapses was restored and the transcription of actin regulators was elevated by MS-275 treatment of Shank3-deficient mice, which may contribute to the recovery of actin-based NMDAR synaptic delivery. Taken together, these results suggest that MS-275 treatment could normalize the aberrant epigenetic regulation of genes, leading to the amelioration of synaptic and social deficits associated with autism.
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16. Miller EK, Lenke LG, Neuman BJ, Sciubba DM, Kebaish KM, Smith JS, Qiu Y, Dahl BT, Pellise F, Matsuyama Y, Carreon LY, Fehlings MG, Cheung KM, Lewis S, Dekutoski MB, Schwab FJ, Boachie-Adjei O, Mehdian H, Bess S, Shaffrey CI, Ames CP. {{External Validation of the Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) in the Scoli-RISK-1 Patient Database}}. {Spine (Phila Pa 1976)};2018 (May 14)
STUDY DESIGN: Analysis of a prospective multicenter database. OBJECTIVE: To assess the ability of the recently created Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) to predict odds of major complications and length of hospital stay for patients who had more severe preoperative deformity and underwent more invasive ASD surgery compared with patients in the database used to create the index. SUMMARY OF BACKGROUND DATA: Accurate preoperative estimates of risk are necessary given the high complication rates currently associated with ASD surgery. METHODS: Patients were enrolled by participating institutions in Europe, Asia, and North America from 2009 to 2011. ASD-FI scores were used to classify 267 patients as not frail (NF) (<0.3), frail (0.3-0. 5), or severely frail (SF) (>0.5). Multivariable logistic regression, adjusted for preoperative and surgical covariates such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and incidence of major complications, overall incidence of complications, and length of hospital stay. RESULTS: The mean ASD-FI score was 0.3 (range, 0-0.7). We categorized 105 patients as NF, 103 as frail, and 59 as SF. The adjusted odds of developing a major complication were higher for SF patients (odds ratio = 4.4; 95% CI 2.0, 9.9) compared with NF patients. After adjusting for covariates, length of hospital stay for SF patients increased by 19% (95% CI 1.4%, 39%) compared with NF patients. The odds of developing a major complication or having increased length of stay were similar between frail and NF patients. CONCLUSIONS: Greater patient frailty, as measured by the ASD-FI, is associated with a longer hospital stay and greater risk of major complications among patients who have severe preoperative deformity and undergo invasive surgical procedures. LEVEL OF EVIDENCE: 2.
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17. Morales-Hidalgo P, Ferrando PJ, Canals J. {{Assessing the heterogeneity of autism spectrum symptoms in a school population}}. {Autism Res};2018 (May 15)
The aim of the present study was to assess whether the nature of the main autistic features (i.e., social communication problems and repetitive and restrictive patterns) are better conceptualized as dimensional or categorical in a school population. The study was based on the teacher ratings of two different age groups: 2,585 children between the ages of 10 and 12 (Primary Education; PE) and 2,502 children between the ages of 3 and 5 (Nursery Education; NE) from 60 mainstream schools. The analyses were based on Factor Mixture Analysis, a novel approach that combines dimensional and categorical features and prevents spurious latent classes from appearing. The results provided evidence of the dimensionality of autism spectrum symptoms in a school age population. The distribution of the symptoms was strongly and positively skewed but continuous; and the prevalence of high-risk symptoms for autism spectrum disorders (ASD) and social-pragmatic communication disorder (SCD) was 7.55% of NE children and 8.74% in PE. A categorical separation between SCD and ASD was not supported by our sample. In view of the results, it is necessary to establish clear cut points for detecting and diagnosing autism and to develop specific and reliable tools capable of assessing symptom severity and functional consequences in children with ASD. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The results of the present study suggest that the distribution of autism spectrum symptoms are continuous and dimensional among school-aged children and thus support the need to establish clear cut-off points for detecting and diagnosing autism. In our sample, the prevalence of high-risk symptoms for autism spectrum disorders and social-pragmatic communication disorder was around 8%.
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18. Nagib W, Williams A. {{Creating « therapeutic landscapes » at home: The experiences of families of children with autism}}. {Health Place};2018 (May 16);52:46-54.
This study explores the challenges faced within the home environment by North American families of children with autism. The study also examines the diversity and extent of physical modifications introduced by the families to alleviate these challenges. The concept of therapeutic landscapes is employed as a framework to examine how physical modifications transform the home environment into a place of healing for both the children with autism and their family members. Finally, the study offers a general design framework that can ultimately guide home designers and policymakers in developing friendly home environments for children with autism and their families.
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19. Osenberg S, Karten A, Sun J, Li J, Charkowick S, Felice CA, Kritzer M, Nguyen MVC, Yu P, Ballas N. {{Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome}}. {Proc Natl Acad Sci U S A};2018 (May 16)
Rett syndrome (RTT) is a severe neurodevelopmental disorder that affects about 1 in 10,000 female live births. The underlying cause of RTT is mutations in the X-linked gene, methyl-CpG-binding-protein-2 (MECP2); however, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. Specifically, although MeCP2 is known to act as a transcriptional repressor, analyses of the RTT brain at steady-state conditions detected numerous differentially expressed genes, while the changes in transcript levels were mostly subtle. Here we reveal an aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity in a mouse model for RTT. Notably, the specific splicing modalities of intron retention and exon skipping displayed a significant bias toward increased retained introns and skipped exons, respectively, in the RTT brain compared with the WT brain. Furthermore, these aberrations occur in conjunction with higher seizure susceptibility in response to neuronal activity in RTT mice. Our findings advance the concept that normal MeCP2 functioning is required for fine-tuning the robust and immediate changes in gene transcription and for proper regulation of alternative splicing induced in response to neuronal stimulation.
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20. Scott M, Falkmer M, Falkmer T, Girdler S. {{Evaluating the Effectiveness of an Autism-Specific Workplace Tool for Employers: A Randomised Controlled Trial}}. {J Autism Dev Disord};2018 (May 16)
A randomised controlled trial evaluated the effectiveness of the Integrated Employment Success Tool (IEST) in improving employers’ self-efficacy in modifying the workplace for individuals on the autism spectrum. Employers (N = 84) were randomised to the IEST or support as usual groups. Measurements of self-efficacy, knowledge and attitudes towards disability in the workplace were obtained at baseline and post-test. Results revealed a significant improvement in self-efficacy within the IEST group between baseline and post-test (p = 0.016). At post-test, there were no significant differences between groups in relation to self-efficacy in implementing autism-specific workplace modifications and employer attitudes towards disability in the workplace. Given the lack of significant outcomes, further research is needed to determine the effectiveness of the IEST for employers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12614000771651, registered 21/7/2014. Trial URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366699 .
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21. Sharma SR, Gonda X, Tarazi FI. {{Autism Spectrum Disorder classification, diagnosis and therapy}}. {Pharmacol Ther};2018 (May 12)
Autism Spectrum Disorder (ASD) refers to a group of neurodevelopmental disorders including autism, Asperger’s syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS). The new diagnostic criteria of ASD focuses on two core domains: social communication impairment and restricted interests/repetitive behaviors. The prevalence of ASD has been steadily increasing over the past two decades, with current estimates reaching up to 1 in 36 children. Hereditary factors, parental history of psychiatric disorders, pre-term births, and fetal exposure to psychotropic drugs or insecticides have all been linked to higher risk of ASD. Several scales such as the Childhood Autism Rating Scale (CARS), The Autism Spectrum Disorder-Observation for Children (ASD-OC), The Developmental, Dimensional, and Diagnostic Interview (3di), are available to aid in better assessing the behaviors and symptoms associated with ASD. Nearly 75% of ASD patients suffer from comorbid psychiatric illnesses or conditions, which may include attention-deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder, depression, Tourette syndrome, and others. Both pharmacological and non-pharmacological interventions are available for ASD. Pharmacological treatments include psychostimulants, atypical antipsychotics, antidepressants, and alpha-2 adrenergic receptor agonists. These medications provide partial symptomatic relief of core symptoms of ASD or manage the symptoms of comorbid conditions. Non-pharmacological interventions, which show promising evidence in improving social interaction and verbal communication of ASD patients, include music therapy, cognitive behavioral therapy and social behavioral therapy. Hormonal therapies with oxytocyin or vasopressin receptor antagonists have also shown some promise in improving core ASD symptoms. The use of vitamins, herbal remedies and nutritional supplements in conjunction with pharmacological and behavioral treatment appear to have some effect in symptomatic improvement in ASD, though additional studies are needed to confirm these benefits. Developing novel disease-modifying therapies may prove to be the ultimate intervention for sustained improvement of symptoms in ASD.
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22. Sheela P, Puthankattil SD. {{Event related potential analysis techniques for autism spectrum disorders: A review}}. {Int J Dev Neurosci};2018 (May 19);68:72-82.
Autism Spectrum Disorders (ASD) comprise all pervasive neurodevelopmental diseases marked by deficits in social and communication skills, delayed cognitive development, restricted and repetitive behaviors. The core symptoms begin in early childhood, may continue life-long resulting in poor performance in adult stage. Event-related potential (ERP) is basically a time-locked electroencephalogram signal elicited by various stimuli, related to sensory and cognitive processes. The various ERP based techniques used for the study of ASD are considered in this review. ERP based study offers the advantage of being a non-invasive technique to measure the brain activity precisely. The techniques are categorized into three based on the processing domain: time, frequency and time-frequency. Power spectral density, coherence, phase synchrony, multiscale entropy, modified multiscale entropy, sum of signed differences, synchrostates and variance are some of the measures that have been widely used to study the abnormalities in frequency bands and brain connectivity. Various signal processing techniques such as Fast Fourier Transform, Discrete Fourier Transform, Short-Time Fourier Transform, Principal Component Analysis, Wavelet Transform, Directed Transfer Function etc. have been used to analyze the recorded signals so as to unravel the distinctive event-related potential patterns in individuals with ASD. The review concludes that ERP proves to be an efficient tool in detecting the brain abnormalities and connectivity issues, indicating the heterogeneity of ASD. Many advanced techniques are utilized to decipher the underlying neural circuitry so as to aid in therapeutic interventions for improving the core areas of deficits.
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23. Smith-Young J, Murray C, Swab M. {{Parents’ and guardians’ experiences of barriers and facilitators in accessing autism spectrum disorder diagnostic services for their children: a systematic review protocol of qualitative evidence}}. {JBI Database System Rev Implement Rep};2018 (May);16(5):1141-1146.
REVIEW QUESTION: What are parents’ and guardians’ experiences of barriers and facilitators in accessing autism spectrum disorder diagnostic services for their children?
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24. Tachibana Y, Miyazaki C, Mikami M, Ota E, Mori R, Hwang Y, Terasaka A, Kobayashi E, Kamio Y. {{Meta-analyses of individual versus group interventions for pre-school children with autism spectrum disorder (ASD)}}. {PLoS One};2018;13(5):e0196272.
There is little evidence regarding the effects of individual and group intervention for children with autism spectrum disorder (ASD) on important outcomes. We performed meta-analyses using a random effects model to investigate the effectiveness of the individual and group intervention studies and to compare the effectiveness of these two types if possible. The main analysis which excluded studies at a high risk of bias (Analysis I) included 14 randomised controlled trials targeting children with ASDLien vers le texte intégral (Open Access ou abonnement)
25. van Esch L, Vanmarcke S, Ceulemans E, Van Leeuwen K, Noens I. {{Parenting adolescents with ASD: A multimethod study}}. {Autism Res};2018 (May 15)
A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially few studies investigated parenting in adolescence, although this period is associated with additional challenges for both adolescents and their parents. In the present study, a multi-method approach was used, combining data from a self-report questionnaire and observation of mother-child interactions during different semi-structured (e.g., inventing and building a vehicle of the future with construction toys) and structured tasks (e.g., solving marble maze). Linear mixed models (LMM) were used to compare the means of parenting behaviors among mothers of adolescents with (n = 44) and without ASD (n = 38), aged 12 to 16 years old. During the observations, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the general population control group. In addition, mothers in the ASD group reported on the self-report questionnaire to adapt the environment more, for example, by establishing routines. Furthermore, this study investigated the role of maternal characteristics, that is, ASD characteristics and parenting stress. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation, and more self-reported harsh punishment and adapting the environment. This study additionally examined whether the impact of these maternal characteristics was the same across the two groups. Whereas group by parenting stress interaction effects were not significant for any of the observed and self-reported parenting behaviors, significant group by ASD characteristics interaction effects were noticed for self-reported harsh punishment and adapting the environment. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially parenting in adolescence remains under investigated, although this period is associated with additional challenges for both adolescents and their parents. In this study, 44 adolescents with ASD and a control group of 38 adolescents without ASD, aged 12-16 years old, participated together with their mother. We compared parenting behaviors between the two groups, based on observations of mother-child interactions and a questionnaire that was filled out by the mother. During the observation, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the control group. In addition, the questionnaire responses indicated that mothers in the ASD group adapted the environment more by for example, establishing routines. Furthermore, this study investigated the role of parenting stress and ASD characteristics of the mother on parenting behavior. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation in both groups, and more self-reported harsh punishment and adapting the environment in the control group only.
