1. {{De Novo Variants Associated With Developmental Disability: Exome sequencing data findings implicate new genes as potential sources of de novo mutations}}. {Am J Med Genet A};2017 (May);173(5):1139-1140.
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2. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Mohammad R, Attia SM. {{Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model}}. {Mol Neurobiol};2017 (Apr 18)
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T+ Itpr3tf/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model. A2A receptors have previously been targeted in clinical trials by potential therapeutics with neuroprotective, immunomodulatory, and analgesic properties. In this study, we examined the effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8+ T cells in the BTBR autistic mouse model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in brain tissue. Our results showed that CCR3+, CCR4+, CCR5+, CCR6+, CCR7+, CXCR3+, CXCR4+, and CXCR5+ production in splenic CD8+ T cells decreased significantly in BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH-treated mice. In addition, RT-PCR analysis revealed decreased gene expression levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS-treated mice, whereas these levels were significantly increased in BTBR control and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS decreases C-C and C-X-C chemokine receptor signaling and might therefore provide a unique avenue for developing future therapies for autism and neuroimmunological disorders.
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3. Bush KL, Tasse MJ. {{Employment and choice-making for adults with intellectual disability, autism, and down syndrome}}. {Res Dev Disabil};2017 (Apr 20);65:23-34.
BACKGROUND: Adults with disabilities are employed at a significantly lower rate than adults without disabilities. Of adults with disabilities in the workforce, more individuals work in a facility setting rather than a community setting, despite efforts to improve community inclusion. Choice-making has been proposed as a predictive factor for employment for individuals with disabilities. AIMS: The purpose of this research was to examine the current state of employment for three groups of adults with intellectual disability (ID): individuals with autism spectrum disorder (ASD), individuals with Down syndrome (DS), and individuals with idiopathic ID. Choice-making and its relation to improved employment outcomes was explored. METHODS: This study used National Core Indicator’s Adult Consumer Survey datasets from years 2011-2012 and 2012-2013. Factor analyses revealed latent variables from six choice-making questions in the Adult Consumer Survey. Ordinal logistic regression was used to identify factors related to employment status. RESULTS: Adults with DS had the highest rates of paid community jobs, but adults with ID had the highest rates of choice-making. ID severity level and short-term choice-making had the greatest effects on employment status in all three groups. CONCLUSIONS: Employment rates remain low despite national efforts to find jobs for people with disabilities. Choice-making is a unique factor that was found to be associated with employment status and provides a target for interventions to increase employability.
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4. Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S. {{Fragile X syndrome: a review of clinical and molecular diagnoses}}. {Ital J Pediatr};2017 (Apr 19);43(1):39.
BACKGROUND: Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more than 99% of individuals have a CGG expansion (>200 triplets) in the 5′ UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures. DISCUSSION: FXS is a well-known condition; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms. CONCLUSIONS: The clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden. Lien vers le texte intégral (Open Access ou abonnement)
5. Diaz-Beltran L, Esteban FJ, Varma M, Ortuzk A, David M, Wall DP. {{Cross-disorder comparative analysis of comorbid conditions reveals novel autism candidate genes}}. {BMC Genomics};2017 (Apr 20);18(1):315.
BACKGROUND: Numerous studies have highlighted the elevated degree of comorbidity associated with autism spectrum disorder (ASD). These comorbid conditions may add further impairments to individuals with autism and are substantially more prevalent compared to neurotypical populations. These high rates of comorbidity are not surprising taking into account the overlap of symptoms that ASD shares with other pathologies. From a research perspective, this suggests common molecular mechanisms involved in these conditions. Therefore, identifying crucial genes in the overlap between ASD and these comorbid disorders may help unravel the common biological processes involved and, ultimately, shed some light in the understanding of autism etiology. RESULTS: In this work, we used a two-fold systems biology approach specially focused on biological processes and gene networks to conduct a comparative analysis of autism with 31 frequently comorbid disorders in order to define a multi-disorder subcomponent of ASD and predict new genes of potential relevance to ASD etiology. We validated our predictions by determining the significance of our candidate genes in high throughput transcriptome expression profiling studies. Using prior knowledge of disease-related biological processes and the interaction networks of the disorders related to autism, we identified a set of 19 genes not previously linked to ASD that were significantly differentially regulated in individuals with autism. In addition, these genes were of potential etiologic relevance to autism, given their enriched roles in neurological processes crucial for optimal brain development and function, learning and memory, cognition and social behavior. CONCLUSIONS: Taken together, our approach represents a novel perspective of autism from the point of view of related comorbid disorders and proposes a model by which prior knowledge of interaction networks may enlighten and focus the genome-wide search for autism candidate genes to better define the genetic heterogeneity of ASD.
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6. Fan J, Wade JW, Key AP, Warren Z, Sarkar N. {{EEG-based Affect and Workload Recognition in a Virtual Driving Environment for ASD Intervention}}. {IEEE Trans Biomed Eng};2017 (Apr 12)
OBJECTIVE: To build group-level classification models capable of recognizing affective states and mental workload of individuals with autism spectrum disorder (ASD) during driving skill training. METHODS: Twenty adolescents with ASD participated in a six-session virtual reality driving simulator based experiment, during which their electroencephalogram (EEG) data were recorded alongside driving events and a therapist’s rating of their affective states and mental workload. Five feature generation approaches including statistical features, fractal dimension features, higher order crossings (HOC)-based features, power features from frequency bands, and power features from bins ( f 2 Hz ) were applied to extract relevant features. Individual differences were removed with a two-step feature calibration method. Finally, binary classification results based on the k-nearest neighbors algorithm and univariate feature selection method were evaluated by leave-one-subject-out nested cross-validation to compare feature types and identify discriminative features. RESULTS: The best classification results were achieved using power features from bins for engagement (0.95) and boredom (0.78), and HOC-based features for enjoyment (0.90), frustration (0.88), and workload (0.86). CONCLUSION: Offline EEG-based group-level classification models are feasible for recognizing binary low and high intensity of affect and workload of individuals with ASD in the context of driving. However, while promising the applicability of the models in an online adaptive driving task requires further development. SIGNIFICANCE: The developed models provide a basis for an EEG-based passive brain computer interface system that has the potential to benefit individuals with ASD with an affect- and workload-based individualized driving skill training intervention.
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7. Friedman C, Owen AL. {{Sexual health in the community: Services for people with intellectual and developmental disabilities}}. {Disabil Health J};2017 (Apr 06)
BACKGROUND: Sexuality is a central dimension of overall health and well-being. People with intellectual and developmental disabilities (IDD) continue to experience disparities in healthcare, particularly regarding access to sexual health related services. Medicaid Home and Community-Based Services (HCBS) waivers are ideally situated to provide sexual and reproductive healthcare in accessible settings. OBJECTIVE: This preliminary study analyzed national Medicaid HCBS waivers to determine how they provide sexuality services for people with IDD. METHODS: 111 FY 2015 HCBS 1915(c) waivers for people with IDD from 46 states and the District of Columbia were analyzed to determine which waivers were providing services related to sexuality. Expenditure and utilization data were analyzed to determine service allotment. RESULTS: Currently, less than 12% of waivers include any kind of sexuality services, and those services provided are predominantly reactive, rather than proactive. Reactive services focused on interrupting sexually inappropriate behaviors through assessments and plans, intervention and therapy, and supervision. Meanwhile, proactive services promoted the healthy sexuality of people with IDD by providing sexuality education related to sexuality awareness, reproduction, and victimization avoidance. CONCLUSIONS: The limited availability of Medicaid HCBS sexuality service provision not only hints at a lack of understanding of sexuality for people with IDD, but also presents an opportunity to perform increased evaluations on current service offerings in order to justify future expanded offerings in other states.
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8. Gibbs VD. {{Detection and Treatment of Autism Spectrum Disorder by Occupational Therapy Practitioners: Addressing Racial Disparity in Diagnosis}}. {Am J Occup Ther};2017 (May/Jun);71(3):7103360010p7103360011-7103360010p7103360014.
As the prevalence of autism spectrum disorder (ASD) continues to rise, racial disparities remain in age of diagnosis and initiation of treatment. Therefore, occupational therapy practitioners should examine cultural perceptions related to disparities in ASD diagnosis. This article investigates the role that practitioners may play in this disparity by asking, « Are occupational therapy practitioners contributing to the late diagnosis of children with ASD who are members of particular racial or ethnic groups? » Correlations among practitioners’ detection of symptoms, parents’ perceptions, and evaluator influences are investigated. By examining these factors, practitioners may gain better insight into these disparities and therefore provide more effective advocacy regarding early diagnosis and treatment access.
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9. Ito H, Mori K, Harada M, Hisaoka S, Toda Y, Mori T, Goji A, Abe Y, Miyazaki M, Kagami S. {{A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum}}. {J Child Neurol};2017 (Jan 01):883073817702981.
The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, gamma-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.
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10. Jansen A, Dieleman GC, Smit AB, Verhage M, Verhulst FC, Polderman TJC, Posthuma D. {{Gene-set analysis shows association between FMRP targets and autism spectrum disorder}}. {Eur J Hum Genet};2017 (Apr 19)
Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding biological mechanisms are largely unknown. Our objective is to investigate the contribution of common genetic variation to biological pathways functionally involved in ASD. We conducted gene-set analyses to identify ASD-associated functional biological pathways using the statistical tools MAGMA and INRICH. Gene-set selection was based on previously reported associations with psychiatric disorders and resulted in testing of specific synaptic and glial sets, a glutamate pathway gene-set, mitochondrial gene-sets and gene-sets consisting of fragile X mental retardation protein (FMRP) targets. In total 32 gene-sets were tested. We used Psychiatric Genomics Consortium genome-wide association studies summary statistics of ASD. The study is based on the largest ASD sample to date (N=5305). We found one significantly associated gene-set consisting of FMRP-targeting transcripts (MAGMA: p corr.=0.014, INRICH: p corr.=0.031; all competitive P-values). The results indicate the involvement of FMRP-targeted transcripts in ASD in common genetic variation. This novel finding is in line with the literature as FMRP has been linked to fragile X syndrome, ASD and cognitive development in whole-exome sequencing and copy number variant studies. This gene-set has also been linked to Schizophrenia suggesting that FMRP-targeted transcripts might be involved in a general mechanism with shared genetic etiology between psychiatric disorders.European Journal of Human Genetics advance online publication, 19 April 2017; doi:10.1038/ejhg.2017.55.
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11. Jones CRG, Lambrechts A, Gaigg SB. {{Using Time Perception to Explore Implicit Sensitivity to Emotional Stimuli in Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Apr 20)
Establishing whether implicit responses to emotional cues are intact in autism spectrum disorder (ASD) is fundamental to ascertaining why their emotional understanding is compromised. We used a temporal bisection task to assess for responsiveness to face and wildlife images that varied in emotional salience. There were no significant differences between an adult ASD and comparison group, with both showing implicit overestimation of emotional stimuli. Further, there was no correlation between overestimation of emotional stimuli and autistic traits in undergraduate students. These data do not suggest a fundamental insensitivity to the arousing content of emotional images in ASD, or in individuals with a high degree of autistic traits. The findings have implications for understanding how emotional stimuli are processed in ASD.
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12. Lim JS, Lim MY, Choi Y, Ko G. {{Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia}}. {Mol Brain};2017 (Apr 20);10(1):14.
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.
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13. Parsons L, Cordier R, Munro N, Joosten A, Speyer R. {{A systematic review of pragmatic language interventions for children with autism spectrum disorder}}. {PLoS One};2017;12(4):e0172242.
There is a need for evidence based interventions for children with autism spectrum disorder (ASD) to limit the life-long, psychosocial impact of pragmatic language impairments. This systematic review identified 22 studies reporting on 20 pragmatic language interventions for children with ASD aged 0-18 years. The characteristics of each study, components of the interventions, and the methodological quality of each study were reviewed. Meta-analysis was conducted to assess the effectiveness of 15 interventions. Results revealed some promising approaches, indicating that active inclusion of the child and parent in the intervention was a significant mediator of intervention effect. Participant age, therapy setting or modality were not significant mediators between the interventions and measures of pragmatic language. The long-term effects of these interventions and the generalisation of learning to new contexts is largely unknown. Implications for clinical practice and directions for future research are discussed.
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14. Schmeisser K, Alex Parker J. {{Worms on the spectrum – C. elegans models in autism research}}. {Exp Neurol};2017 (Apr 20)
The small non-parasitic nematode Caenorhabditis elegans is widely used in neuroscience thanks to its well-understood development and lineage of the nervous system. Furthermore, C. elegans has been used to model many human developmental and neurological conditions to better understand disease mechanisms and identify potential therapeutic strategies. Autism spectrum disorder (ASD) is the most prevalent of all neurodevelopmental disorders, and the C. elegans system may provide opportunities to learn more about this complex disorder. Along with a repertoire of behaviours, since basic cell biology and biochemistry of the C. elegans nervous system is generally very similar to mammals, cellular or molecular phenotypes can be investigated. For instance, worms have contributed greatly to the understanding of mechanisms underlying mutations in genes coding for synaptic proteins such as neuroligin and neurexin. However, using worms to model neurodevelopmental disorders like ASD, is still an emerging topic that harbours great, untapped potential. This review summarizes the numerous contributions of C. elegans to the field of biology and introduces the nematode system as a potential research tool to study essential roles of genes associated with ASD.
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15. Su X, Yuan W, Chen J, Miao M, Olsen J, Pedersen LH, Liang H, Li J. {{Prenatal exposure to beta2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring}}. {Pharmacoepidemiol Drug Saf};2017 (Apr 19)
PURPOSE: We aimed to examine the risk of autism spectrum disorders (ASDs) in the offspring who were exposed to maternal use of beta2-adrenoreceptor agonist (beta2AA) during pregnancy. METHODS: This is a population-based cohort study including all live singleton births in Denmark from 1 January 1997 to 31 December 2008. Children born to mothers who used beta2AA during pregnancy were categorized as exposed, and all other children were included in the unexposed group. Cases of ASDs were identified from the Danish Psychiatric Central Register and the Danish Patient Register. Incidence rate ratio (IRR) and 95% confidence interval were estimated by Poisson regression models. RESULTS: Among 751 888 children in the cohort, 9098 (1.21%) received a diagnosis of ASDs. We observed an increased risk of ASDs in the exposed children (IRR = 1.28, 1.11-1.47), especially for those who were exposed during the second trimester period (IRR = 1.38, 1.14-1.67). However, when extending the exposure time window to 1 year prior to pregnancy, we observed a similar association in children born to women who received beta2AA treatment during pregnancy (IRR = 1.33, 1.11-1.59) to that in children born to women who received beta2AA treatment 1 year prior to pregnancy (IRR = 1.35, 1.17-1.56). CONCLUSION: Our finding suggested that children born to women who used beta2AA during pregnancy have an increased risk of ASDs in later life, which is more likely due to underlying maternal diseases rather than the exposure to beta2AA itself. However, further study, which would better differentiate the effects between indication and medicine, is needed to corroborate the finding. Copyright (c) 2017 John Wiley & Sons, Ltd.
