1. Barahona-Correa JB, Velosa A, Chainho A, Lopes R, Oliveira-Maia AJ. {{Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis}}. {Frontiers in integrative neuroscience}. 2018; 12: 27.
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD. Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed. Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time. Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.
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2. Carrette LLG, Blum R, Ma W, Kelleher RJ, 3rd, Lee JT. {{Tsix-Mecp2 female mouse model for Rett syndrome reveals that low-level MECP2 expression extends life and improves neuromotor function}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2018.
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a mutation in the X-linked methyl-CpG-binding protein 2 (MECP2). There is currently no disease-specific treatment, but MECP2 restoration through reactivation of the inactive X (Xi) has been of considerable interest. Progress toward an Xi-reactivation therapy has been hampered by a lack of suitable female mouse models. Because of cellular mosaicism due to random X-chromosome inactivation (XCI), Mecp2(+/-) heterozygous females develop only mild RTT. Here, we create an improved female mouse model by introducing a mutation in Tsix, the antisense regulator of XCI allelic choice. Tsix-Mecp2 mice show reduced MECP2 mosaicism and closely phenocopy the severely affected Mecp2-null males. Tsix-Mecp2 females demonstrate shortened lifespan, motor weakness, tremors, and gait disturbance. Intriguingly, they also exhibit repetitive behaviors, as is often seen in human RTT, including excessive grooming and biting that result in self-injury. With a Tsix allelic series, we vary MECP2 levels in brain and demonstrate a direct, but nonlinear correlation between MECP2 levels and phenotypic improvement. As little as 5-10% MECP2 restoration improves neuromotor function and extends lifespan five- to eightfold. Our study thus guides future pharmacological strategies and suggests that partial MECP2 restoration could have disproportionate therapeutic benefit.
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3. Cooper A, Ireland D. {{Designing a Chat-Bot for Non-Verbal Children on the Autism Spectrum}}. {Studies in health technology and informatics}. 2018; 252: 63-8.
There is a significant amount of anecdotal evidence of the benefits of individuals on the autism spectrum interacting with technology via natural language. Many of these individuals are non-verbal but still able to communicate via augmentative and alternative communication (AAC) aids. This paper presents the design of a AAC software program (app) with embedded artificial conversational agent, called Alex. Alex runs on a Android device and is able to engage with the user on a variety of topics using symbols and images. Alex may be programmed via speech and occupational therapists and other key stakeholders via speech and hence does not require any specialised computer skills. The importance of customisation, interoperability, personalisation and motor skill considerations is herein discussed.
4. Cvejic RC, Hocking DR, Wen W, Georgiou-Karistianis N, Cornish KM, Godler DE, Rogers C, Trollor JN. {{Reduced caudate volume and cognitive slowing in men at risk of fragile X-associated tremor ataxia syndrome}}. {Brain Imaging Behav}. 2018.
Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings provide preliminary evidence that early reductions in caudate volume may be associated with cognitive slowing in men with the premutation who do not present with cardinal motor signs of FXTAS. If confirmed in future studies with larger PM cohorts, these findings will have important implications for the identification of sensitive measures with potential utility for tracking cognitive decline. Lien vers le texte intégral (Open Access ou abonnement)
5. Edwards KA, Madden AMK, Zup SL. {{Serotonin receptor regulation as a potential mechanism for sexually dimorphic oxytocin dysregulation in a model of Autism}}. {Brain Res}. 2018.
Perinatal administration of serotonin (5HT) agonist 5-methoxytryptamine (5MT) induces developmental hyperserotonemia (DHS; elevated blood serotonin) and produces behavioral and neurochemical changes in rats relevant to Autism Spectrum Disorder (ASD), such as oxytocin dysregulation. Disruption of the oxytocin system may underlie many of the social deficits present in ASD individuals, thus we investigated the mechanism(s) underlying DHS-induced oxytocin dysregulation. The most parsimonious mechanism of 5HT action would be via alteration of 5HT receptors on oxytocin cells; 5HT is known to influence cell survival as well as influence oxytocin release via 5HT1A and 5HT2A receptors, which co-localize in oxytocin-expressing (OXT+) cells in the paraventricular nucleus (PVN) of the hypothalamus. We report that both male and female DHS rats have a lower percentage of OXT+ cells co-localized with excitatory 5HT2A receptors than control animals, while only DHS females have a higher percentage of OXT+ cells co-localized with inhibitory 5HT1A receptors compared to controls. Importantly, DHS also reduces the number of OXT+ cells in the PVN of adult male, but not female, rats. This pattern suggests that females, but not males, can regulate 5HT receptors in response to DHS in a manner that promotes oxytocin cell survival and functional efficiency. In addition, it has been previously reported that DHS alters normal juvenile play, especially in males, thus we also tested play partner preference among juvenile control and DHS males. Sex differences observed using the DHS model of ASD add to its validity, given the pronounced male sex bias in the prevalence of ASD, and emphasize the need for inclusion of both sexes in ASD research.
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6. Franchini M, Armstrong VL, Schaer M, Smith IM. {{Initiation of joint attention and related visual attention processes in infants with autism spectrum disorder: Literature review}}. {Child Neuropsychol}. 2018: 1-31.
Autism spectrum disorder (ASD) represents a group of neurodevelopmental disabilities that can be difficult to identify before the age of 2 or 3 years, the age when the full range of behavioral symptoms has emerged in most cases. Initiation of joint attention is an important developmental function in which impairments are already observable before the second birthday and can predict children’s ASD symptomatology. In the first part of this review, we summarize results pertaining to retrospective studies of initiation of joint attention in children with ASD and prospective studies of infants at high risk for ASD during the first 2 years, when this behavior is becoming more complex in terms of frequency, quality, and variety. We will also discuss the implications of impairments in dyadic engagement, a precursor of joint attention behavior, for the early development of joint attention. Finally, the early development of initiation of joint attention has been related to specific visual attention mechanisms such as social orienting and visual disengagement. In the second part of this review, we provide an overview of the relationship between those visual attention mechanisms and subsequent social-communication impairments. Clinical and research implications of these findings for both early detection and early intervention will be discussed.
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7. Guo C, Luo M, Wang X, Huang S, Meng Z, Shao J, Zhang X, Shao Z, Wu J, Robins DL, Jing J. {{Reliability and Validity of the Chinese Version of Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F)}}. {J Autism Dev Disord}. 2018.
Although early detection of autism facilitates intervention, early detection strategies are not yet widespread in China. To improve the situation, the Chinese version of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) was validated. The sample included 7928 toddlers, aged 16 to 30 months, screened during their routine care in six provinces of China. When the cut-off value was 3, the sensitivity and specificity of M-CHAT-R were 0.963 and 0.865. The inter-rater reliability and the test-retest reliability were also adequate (intraclass correlation coefficients were 0.853 and 0.759, both ps < .01). The Chinese version of M-CHAT-R/F is an effective tool for early detection of ASD and is applicable to early screening in China. Lien vers le texte intégral (Open Access ou abonnement)
8. Keith JM, Jamieson JP, Bennetto L. {{The Influence of Noise on Autonomic Arousal and Cognitive Performance in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
This study examined the impact of noise on cognitive performance in autism spectrum disorder (ASD), while concurrently measuring sympathetic responses. Adolescents with and without ASD completed visually presented span tasks in a 2 x 2 experimental manipulation of noise (quiet vs. 75 dB gated broadband noise) and task difficulty (easier vs. harder). Analyses revealed a significant noise x difficulty interaction on performance, and a significant group x noise x difficulty interaction on sympathetic arousal. Correlational analyses indicated an adaptive effect of noise and increased arousal on performance in the easier condition for the control group and a detrimental effect of noise and increased arousal in the harder condition for the ASD group. Implications for sensory processing research and intervention development are discussed.
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9. Lobregt-van Buuren E, Sizoo B, Mevissen L, de Jongh A. {{Eye Movement Desensitization and Reprocessing (EMDR) Therapy as a Feasible and Potential Effective Treatment for Adults with Autism Spectrum Disorder (ASD) and a History of Adverse Events}}. {J Autism Dev Disord}. 2018.
The study investigated whether EMDR is a feasible therapy for adults with ASD and a history of adverse events, and whether it is associated with reductions in symptoms of PTSD, psychological distress and autism. Participants received 6 to 8 weeks treatment as usual (TAU), followed by a maximum of 8 sessions EMDR added to TAU, and a follow-up of 6-8 weeks with TAU only. Results showed a significant reduction of symptoms of post-traumatic stress (IES-R: d = 1.16), psychological distress (BSI: d = 0.93) and autistic features (SRS-A: d = 0.39). Positive results were maintained at follow-up. The results suggest EMDR therapy to be a feasible and potentially effective treatment for individuals with ASD who suffer from the consequences of exposure to distressing events.
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10. Padmanabha H, Singhi P, Sahu JK, Malhi P. {{Home-based Sensory Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial}}. {Indian journal of pediatrics}. 2018.
OBJECTIVES: To determine the feasibility and efficacy of home-based sensory interventions in children with Autism spectrum disorder (ASD) with sensory processing abnormalities. METHODS: This was a 12-wk, parallel group, pilot, randomized controlled trial. During the study-period, 185 children with ASD between 3-12 y of age, with sensory processing abnormalities were screened for eligibility. Twenty-one children were randomly assigned to the sensory-intervention group and 19 to the standard-therapy group. Sensory-intervention group received home-based sensory interventions by the parents/caregivers plus standard therapy; standard-therapy group received speech therapy by the speech pathologists and applied behavior analysis by the child psychologist. RESULTS: The mean change in scores at baseline and 12 wk into intervention showed that children in sensory-intervention group (Mean = 9.33, SD = 3.52) scored significantly better on Parent Rated 10-item Likert Scale (PRILS-10), as compared to standard-therapy group (Mean = 2.47, SD = 1.46), t(36) = 8.16, p < 0.001; d = 2.54. Marked improvement was noted especially in reduction of hyperactivity, motor-stereotypies and auditory sensitivity in those who underwent sensory interventions. The mean change in scores in sensory-intervention group on Children's Global Assessment Scale (CGAS) (Mean = -9.19, SD = 2.33, p < 0.011; d = -1.75) and Pediatric Quality of Life Inventory 4.0 (PedsQL(TM)) (M = -10.53, SD = 5.34, p = 0.008; d = -0.88) showed significant difference in the sensory-intervention group as compared to standard-therapy group. Overall, there was 32.3%, 18.1% and 15.8% improvement on PRILS-10, CGAS and PedsQL(TM) respectively in sensory-intervention group. CONCLUSIONS: The present findings suggest that home-based sensory interventions are feasible in a developing country and are suggested to have a beneficial role in ASD. Lien vers le texte intégral (Open Access ou abonnement)
11. Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. {{Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder}}. {Molecular diagnosis & therapy}. 2018.
Autism spectrum disorder (ASD) affects ~ 2% of children in the United States. The etiology of ASD likely involves environmental factors triggering physiological abnormalities in genetically sensitive individuals. One of these major physiological abnormalities is mitochondrial dysfunction, which may affect a significant subset of children with ASD. Here we systematically review the literature on human studies of mitochondrial dysfunction related to ASD. Clinical aspects of mitochondrial dysfunction in ASD include unusual neurodevelopmental regression, especially if triggered by an inflammatory event, gastrointestinal symptoms, seizures, motor delays, fatigue and lethargy. Traditional biomarkers of mitochondrial disease are widely reported to be abnormal in ASD, but appear non-specific. Newer biomarkers include buccal cell enzymology, biomarkers of fatty acid metabolism, non-mitochondrial enzyme function, apoptosis markers and mitochondrial antibodies. Many genetic abnormalities are associated with mitochondrial dysfunction in ASD, including chromosomal abnormalities, mitochondrial DNA mutations and large-scale deletions, and mutations in both mitochondrial and non-mitochondrial nuclear genes. Mitochondrial dysfunction has been described in immune and buccal cells, fibroblasts, muscle and gastrointestinal tissue and the brains of individuals with ASD. Several environmental factors, including toxicants, microbiome metabolites and an oxidized microenvironment are shown to modulate mitochondrial function in ASD tissues. Investigations of treatments for mitochondrial dysfunction in ASD are promising but preliminary. The etiology of mitochondrial dysfunction and how to define it in ASD is currently unclear. However, preliminary evidence suggests that the mitochondria may be a fruitful target for treatment and prevention of ASD. Further research is needed to better understand the role of mitochondrial dysfunction in the pathophysiology of ASD.
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12. Sweeten TL, Croen LA, Windham GC, Odell JD, Stubbs EG, Torres AR. {{Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls}}. {J Autism Dev Disord}. 2018.
Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.
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13. Zhao Y, Pan Q, Du C. {{Logistic Regression Augmented Community Detection for Network Data with Application in Identifying Autism-Related Gene Pathways}}. {Biometrics}. 2018.
When searching for gene pathways leading to specific disease outcomes, additional information on gene characteristics is often available that may facilitate to differentiate genes related to the disease from irrelevant background when connections involving both types of genes are observed and their relationships to the disease are unknown. We propose method to single out irrelevant background genes with the help of auxiliary information through a logistic regression, and cluster relevant genes into cohesive groups using the adjacency matrix. Expectation-maximization algorithm is modified to maximize a joint pseudolikelihood assuming latent indicators for relevance to the disease and latent group memberships as well as Poisson or multinomial distributed link numbers within and between groups. A robust version allowing arbitrary linkage patterns within the background is further derived. Asymptotic consistency of label assignments under the stochastic blockmodel is proven. Superior performance and robustness in finite samples are observed in simulation studies. The proposed robust method identifies previously missed gene sets underlying autism related neurological diseases using diverse data sources including de novo mutations, gene expressions and protein-protein interactions. This article is protected by copyright. All rights reserved.
