Pubmed du 11/11/19

lundi 11 novembre 2019

1. Allely CS, Kennedy S, Warren I. A legal analysis of Australian criminal cases involving defendants with autism spectrum disorder charged with online sexual offending. Int J Law Psychiatry ;2019 (Sep - Oct) ;66:101456.

This paper examines how the symptomology of the small number of individuals with autism spectrum disorder (ASD) charged with online sexual offenses in Australia is established during legal arguments and conceived by the judiciary to impact legal liability and offending behavior. This study aims to provide empirical support for the proposition that judicial discourses regarding the connection between ASD and online sexual offending, including conduct related to child exploitation material (CEM), have little bearing on overall questions of criminal liability or the use of alternative penal dispositions. It does so by exploring a sample of nine recent Australian criminal cases, involving ten rulings, that examine how evidence of ASD is raised in legal arguments in ways that suggest a diagnosed condition may have contributed significantly to the alleged wrongdoing. We conclude by suggesting current Australian judicial practice requires more sensitivity to the impact of clinical factors associated with ASD in shaping alternative supervisory and non-custodial dispositions for individuals convicted of online sexual offenses.

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2. Alshammari MK, AlKhulaifi MM, Al Farraj DA, Somily AM, Albarrag AM. Incidence of Clostridium perfringens and their toxin genes in the gut of children with autism spectrum disorder. Anaerobe ;2019 (Nov 5):102114.

This study was designed to determine the incidence of Clostridium perfringens and their toxin genes in children with autism spectrum disorder (ASD), and determine the antimicrobial susceptibility of C. perfringens isolates. A hundred and fourteen fecal samples were obtained from children aged 3-12 years old (57 samples from ASD children and 57 from healthy controls). Children were divided into four groups based on their gastrointestinal (GI) symptoms as follows : ASD group with and without GI symptoms, and control group with and without GI symptoms. Selective anaerobic media and VITEK(R)2 ANC ID card were used for isolation and identification of C. perfringens from fecal samples. Antimicrobial susceptibility of C. perfringnes isolates were performed using (E-Test) strips against clindamycin, penicillin and metronidazole antibiotics. Conventional PCR was used to detect the alpha toxin gene (Cpa) and the beta-2 toxin gene (Cpb2). Genetic Analyzer 3130Xi was used to confirm the sequencing of Cpb2 gene. Our findings indicated that 38.6% of ASD group samples had a significantly (p=0.003) higher incidence of C. perfringens than that of the control group (14%). The highest incidence of C. perfringens was found in the ASD group with GI symptoms (53.8% ; p=0.001). C. perfringens isolated from the ASD group (54.5%) were significantly (p=0.047) more resistant to clindamycin than those isolated from the control group (12.5%). The C. perfringens isolates from the ASD and the control group showed 95.5% and 100% susceptibility to penicillin, respectively. All C. perfringens isolates of ASD and control group were susceptible to metronidazole. The Cpa toxin gene was also detected in all the C. perfringens isolates of ASD and control group, both with and without GI symptoms. Cpb2 toxin gene showed 100% incidence in ASD samples with GI symptoms and in the control groups both with or without GI symptoms, while it was present at significantly lower levels (25%) in the ASD samples without GI symptoms (p=0.001). Our findings suggests that a high incidence of C. perfringens and its toxin gene (Cpb2) are associated with the GI complications in ASD which may affect the severity of the disease.

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3. Belmadani M, Jacobson M, Holmes N, Phan M, Nguyen T, Pavlidis P, Rogic S. VariCarta : A Comprehensive Database of Harmonized Genomic Variants Found in Autism Spectrum Disorder Sequencing Studies. Autism Res ;2019 (Nov 9)

Recent years have seen a boom in the application of the next-generation sequencing technology to the study of human disorders, including Autism Spectrum Disorder (ASD), where the focus has been on identifying rare, possibly causative genomic variants in ASD individuals. Because of the high genetic heterogeneity of ASD, a large number of subjects is needed to establish evidence for a variant or gene ASD-association, thus aggregating data across cohorts and studies is necessary. However, methodological inconsistencies and subject overlap across studies complicate data aggregation. Here we present VariCarta, a web-based database developed to address these challenges by collecting, reconciling, and consistently cataloging literature-derived genomic variants found in ASD subjects using ongoing semi-manual curation. The careful manual curation combined with a robust data import pipeline rectifies errors, converts variants into a standardized format, identifies and harmonizes cohort overlaps, and documents data provenance. The harmonization aspect is especially important since it prevents the potential double counting of variants, which can lead to inflation of gene-based evidence for ASD-association. The database currently contains 170,416 variant events from 10,893 subjects, collected across 61 publications, and reconciles 16,202 variants that have been reported in literature multiple times. VariCarta is freely accessible at http://varicarta.msl.ubc.ca. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The search for genetic factors underlying Autism Spectrum Disorder (ASD) yielded numerous studies reporting potentially causative genomic variants found in ASD individuals. However, methodological differences and subject overlap across studies complicate the assembly of these data, diminishing its utility and accessibility. We developed VariCarta, a web-based database that aggregates carefully curated, annotated, and harmonized literature-derived variants identified in individuals with ASD using ongoing semi-manual curation.

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4. Claeys T, Boogers A, Vanneste D. MRI findings in fragile X-associated tremor/ataxia syndrome. Acta Neurol Belg ;2019 (Nov 9)

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5. Fu H, Deng W, Yao L, Gong M, Lai S, Liu J, Li M, Xu H, Wang J. Urinary NOx, a novel potential biomarker for autism spectrum disorder. Free Radic Biol Med ;2019 (Nov 7)

Nitric oxide (NO) participates in many physiological and pathological processes in human. Urine tests tell a lot about health, which are convenient and harmless. Redox stress, including imbalance of reactive nitrogen species and its metabolites NOx, has been gaining increased attention in autism spectrum disorder (ASD) research. However, concentrations of urinary nitrite and nitrate among the ASD population stay unclear. In this study, nitrite and nitrate were precisely measured in urine specimens from 44 ASD children, 30 healthy children (the control group) and 28 healthy adults with an optimized and validated analytic method. For the first time, concentrations of urinary NOx in ASD and healthy children were reported. Nitrite in the ASD population is higher than in the control group, with concentrations of 0.8708+/-0.1121muM (0.1556-3.0393muM) and 0.5938+/-0.07276muM (0.1134-2.1004muM) (p=0.0420), respectively. Nitrite in the adult groups is 0.5808+/-0.0985muM (0.0808-1.9335muM), which is similar to that in the control group. On the contrary, urinary nitrate concentration in ASD children is lower than that in the control group, which are 2.875+/-0.2716mM (0.3264-7.1835mM) and 4.558+/-0.5915mM (1.1860-15.8555mM) (p=0.0133), respectively. Nitrate in adults is also significantly lower than that in the control, 2.799+/-0.3640mM (0.2507-8.6978mM) and 4.558+/-0.5915mM (p=0.0146), respectively. Nitrite/nitrate ratios for ASD and the control groups were 0.3496+/-0.04382 x 10(-3) and 0.1604+/-0.01862 x 10(-3) (p=0.0002), which again indicated the probability of NOx as a novel biomarker. Furthermore, no correlation between NOx and gender, as well as sample collection timing was found. Taken together, the association between NOx and ASD was significant. Urinary nitrite, nitrate and NO2(-)/NO3(-), might serve as a new biomarker for ASD diagnosis during pursuit of harmless, fast, and convenient diagnostic method. Further studies are needed for the metabolic pathways of NOx in ASD pathogenesis.

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6. Gilbert J, O’Connor M, Templet S, Moghaddam M, Di Via Ioschpe A, Sinclair A, Zhu LQ, Xu W, Man HY. NEXMIF/KIDLIA knockout mouse demonstrates autism-like behaviors, memory deficits, and impairments in synapse formation and function. J Neurosci ;2019 (Nov 8)

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, communication deficits, and restrictive and repetitive behaviors. ASD has a strong genetic basis and many ASD-associated genes have been discovered thus far. Our previous work has shown that loss of expression of the X-linked gene NEXMIF/KIDLIA is implicated in patients with autistic features and intellectual disability (ID). To further determine the causal role of the gene in the disorder, and to understand the cellular and molecular mechanisms underlying the pathology, we have generated a NEXMIF knockout (KO) mouse. We find that male NEXMIF KO mice demonstrate reduced sociability and communication, elevated repetitive grooming behavior, and deficits in learning and memory. Loss of NEXMIF/KIDLIA expression results in a significant decrease in synapse density and synaptic protein expression. Consistently, male KO animals show aberrant synaptic function as measured by excitatory miniatures and post-synaptic currents in the hippocampus. These findings indicate that NEXMIF KO mice recapitulate the phenotypes of the human disorder. The NEXMIF KO mouse model will be a valuable tool for studying the complex mechanisms involved in ASD and for the development of novel therapeutics for this disorder.SIGNIFICANCE STATEMENTAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by behavioral phenotypes. Based on our previous work, which indicated the loss of NEXMIF/KIDLIA was associated with ASD, we generated NEXMIF knockout (KO) mice. The NEXMIF KO mice demonstrate autism-like behaviors including deficits in social interaction, increased repetitive self-grooming, and impairments in communication and in learning and memory. The KO neurons show reduced synapse density and a suppression in synaptic transmission, indicating a role for NEXMIF in regulating synapse development and function. The NEXMIF KO mouse faithfully recapitulates the human disorder, and thus serves as an animal model for future investigation of the NEXMIF-dependent neurodevelopmental disorders.

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7. Gordon A, Forsingdal A, Klewe IV, Nielsen J, Didriksen M, Werge T, Geschwind DH. Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations. Mol Psychiatry ;2019 (Nov 8)

Genetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown. Further, whether some of the molecular changes identified in brain relate to potentially confounding antemortem or postmortem factors are difficult to prove. We analyzed the transcriptome from the cortex and hippocampus of three mouse lines modeling human copy number variants (CNVs) associated with schizophrenia and ASD : Df(h15q13)/+, Df(h22q11)/+, and Df(h1q21)/+ which carry the 15q13.3 deletion, 22q11.2 deletion, and 1q21.1 deletion, respectively. Although we found very little overlap of differential expression at the level of individual genes, gene network analysis identified two cortical and two hippocampal modules of co-expressed genes that were dysregulated across all three mouse models. One cortical module was associated with neuronal energetics and firing rate, and overlapped with changes identified in postmortem human brain from SCZ and ASD patients. These data highlight aspects of convergent gene expression in mouse models harboring major risk alleles, and strengthen the connection between changes in neuronal energetics and neuropsychiatric disorders in humans.

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8. Hegarty JP, Lazzeroni LC, Raman MM, Pegoraro LFL, Monterrey JC, Cleveland SC, Hallmayer JF, Wolke ON, Phillips JM, Reiss AL, Hardan AY. Genetic and Environmental Influences on Lobar Brain Structures in Twins With Autism. Cereb Cortex ;2019 (Nov 11)

This investigation examined whether the variation of cerebral structure is associated with genetic or environmental factors in children with autism spectrum disorder (ASD) compared with typically developing (TD) controls. T1-weighted magnetic resonance imaging scans were obtained from twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or both were TD. Good quality data were available from 30 ASD, 18 discordant, and 34 TD pairs (n = 164). Structural measures (volume, cortical thickness, and surface area) were generated with FreeSurfer, and ACE modeling was completed. Lobar structures were primarily genetically mediated in TD twins (a2 = 0.60-0.89), except thickness of the temporal (a2 = 0.33 [0.04, 0.63]) and occipital lobes (c2 = 0.61 [0.45, 0.77]). Lobar structures were also predominantly genetically mediated in twins with ASD (a2 = 0.70-1.00) ; however, thickness of the frontal (c2 = 0.81 [0.71, 0.92]), temporal (c2 = 0.77 [0.60, 0.93]), and parietal lobes (c2 = 0.87 [0.77, 0.97]), and frontal gray matter (GM) volume (c2 = 0.79 [0.63, 0.95]), were associated with environmental factors. Conversely, occipital thickness (a2 = 0.93 [0.75, 1.11]) did not exhibit the environmental contributions that were found in controls. Differences in GM volume were associated with social communication impairments for the frontal (r = 0.52 [0.18, 0.75]), temporal (r = 0.61 [0.30, 0.80]), and parietal lobes (r = 0.53 [0.19, 0.76]). To our knowledge, this is the first investigation to suggest that environmental factors influence GM to a larger extent in children with ASD, especially in the frontal lobe.

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9. Kaufmann WE, Sprouse J, Rebowe N, Hanania T, Klamer D, Missling CU. ANAVEX(R)2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav ;2019 (Nov 5) ;187:172796.

Rett syndrome (RTT) is a severe neurodevelopmental disorder that is associated in most cases with mutations in the transcriptional regulator MECP2. At present, there are no effective treatments for the disorder. Despite recent advances in RTT genetics and neurobiology, most drug development programs have focused on compounds targeting the IGF-1 pathway and no pivotal trial has been completed as yet. Thus, testing novel drugs that can ameliorate RTT’s clinical manifestations is a high priority. ANAVEX2-73 (blarcamesine) is a Sigma-1 receptor agonist and muscarinic receptor modulator with a strong safety record and preliminary evidence of efficacy in patients with Alzheimer’s disease. Its role in calcium homeostasis and mitochondrial function, cellular functions that underlie pathological processes and compensatory mechanisms in RTT, makes blarcamesine an intriguing drug candidate for this disorder. Mice deficient in MeCP2 have a range of physiological and neurological abnormalities that mimic the human syndrome. We tested blarcamesine in female heterozygous mice carrying one null allele of Mecp2 (HET) using a two-tier approach, with age-appropriate tests. Administration of the drug to younger and older adult mice resulted in improvement in multiple motor, sensory, and autonomic phenotypes of relevance to RTT. The latter included motor coordination and balance, acoustic and visual responses, hindlimb clasping, and apnea in expiration. In line with previous animal and human studies, blarcamesine also showed a good safety profile in this mouse model of RTT. Clinical studies in RTT with blarcamesine are ongoing.

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10. Kim JW, Kim HW, Moon DS, Lim YS, McDougle CJ, Howe YJ. Comparison of Services for Autism Spectrum Disorder in Massachusetts with Those in Seoul. J Korean Med Sci ;2019 (Nov 11) ;34(43):e288.

BACKGROUND : This article intended to identify and describe areas in need of services and interventions for individuals with autism spectrum disorder (ASD) and their families in Seoul, Korea. METHODS : A descriptive comparison was made between available services and interventions in Seoul, Korea and Massachusetts, USA. Relevant information was obtained through sending phone/email inquiries to the governments and organizations, visiting their official websites, and searching for published articles or reports. RESULTS : In a few areas such as level of education, economy, and general quality of healthcare, Seoul was found to be similar to Massachusetts. However, in terms of services and interventions for individuals with ASD and their families, especially early identification and intervention, special education, care coordination, school-based programs, and transition to adulthood, Massachusetts was shown to have far more availability. CONCLUSION : The limited availability of services and interventions for individuals with ASD and their families in Seoul in comparison to Massachusetts, underlines target areas for further investment and development.

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11. Liao X, Li Y. Economic burdens on parents of children with autism : a literature review. CNS Spectr ;2019 (Nov 11):1-7.

This review aims to summarize evidence from published articles regarding the economic burdens on parents of children diagnosed with autism to elaborate on current research status, discern key findings and provide suggestions for future studies. A total of 1024 records were identified through our systematic literature research, and 33 studies were included in the review. The 33 included studies reported findings from 10 different countries around the world. These articles (published from 2003 to 2017) used a variety of research methods, including quantitative (n = 26), qualitative (n = 4), and mixed (n = 3) study designs. In summary, parents of autistic children were susceptible to adverse employment impacts and increased financial burdens, especially mothers. More attention should be given to the development of appropriate medical resource allocation and the alleviation of economic burdens on parents of children with autism.

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12. Neupane KG. Autism Spectrum Disorder : The Parental Experience. J Psychosoc Nurs Ment Health Serv ;2019 (Nov 11):1-6.

In 2018, one in every 59 children was diagnosed in the United States with autism spectrum disorder (ASD). ASD is a developmental disability, which is a biologically based neurodevelopmental disorder that affects a child’s social interaction and communication skills. ASD includes repetitive patterns and restrictive behaviors, which could last a lifetime. Limited awareness of disease condition, less effective coping strategies, and inadequate guidance lead to increased stress levels among parents of children with ASD. Parents experience peaks and troughs of social, emotional, and financial challenges as they go through a pre-diagnosis phase, diagnosis phase, and post-diagnosis phase. The shortage of health care providers and fragmentation of care in the health care delivery system delays early diagnosis and management of ASD. Primary care providers along with the U.S. physician workforce for patients with ASD are strongly encouraged to review their practices on early screening and diagnosis and have clearly planned out care for every child with a family-centered approach. [Journal of Psychosocial Nursing and Mental Health Services, x(x), xx-xx.].

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13. Okumura T, Kumazaki H, Singh AK, Touhara K, Okamoto M. Individuals With Autism Spectrum Disorder Show Altered Event-Related Potentials in the Late Stages of Olfactory Processing. Chem Senses ;2019 (Nov 11)

Atypical sensory reactivities are pervasive among people with autism spectrum disorder (ASD). With respect to olfaction, most previous studies have used psychophysical or questionnaire-based methodologies ; thus, the neural basis of olfactory processing in ASD remains unclear. This study aimed to determine the stages of olfactory processing that are altered in ASD. Fourteen young adults with high-functioning ASD (mean age, 21 years ; 3 females) were compared with 19 age-matched typically developing (TD) controls (mean age, 21 years ; 4 females). Olfactory event-related potentials (OERPs) for 2-phenylethyl alcohol-a rose-like odor-were measured with 64 scalp electrodes while participants performed a simple odor detection task. Significant group differences in OERPs were found in 3 time windows 542 ms after the stimulus onset. The cortical source activities in these time windows, estimated using standardized low-resolution brain electromagnetic tomography, were significantly higher in ASD than in TD in and around the posterior cingulate cortex, which is known to play a crucial role in modality-general cognitive processing. Supplemental Bayesian analysis provided substantial evidence for an alteration in the later stages of olfactory processing, whereas conclusive evidence was not provided for the earlier stages. These results suggest that olfactory processing in ASD is altered at least at the later, modality-general processing stage.

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14. Palser ER, Fotopoulou A, Pellicano E, Kilner JM. Dissociation in How Core Autism Features Relate to Interoceptive Dimensions : Evidence from Cardiac Awareness in Children. J Autism Dev Disord ;2019 (Nov 9)

Interoception in autism is receiving increasing research attention. Previously, differences were identified in autism on both objective and subjective measures of interoception, and an association with anxiety. Yet, it is currently unknown how interoception relates to core autism features. Here, in 49 autistic children, we consider how interoceptive accuracy (measured with heartbeat detection tasks) and sensibility (subjective judgements of awareness) relate to overall severity on the Autism Diagnostic Observation Schedule, and symptom domains of social-affective and repetitive, restricted behaviors. Socio-affective features were related to interoceptive sensibility, while repetitive restricted behaviors were related to interoceptive accuracy. This dissociation suggests disparate interoceptive mechanisms for the formation and/or maintenance of autistic features.

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15. Pavone P, Corsello G, Marino SD, Ruggieri M, Falsaperla R. 7q31.32 partial duplication : First report of a child with dysmorphism, autistic spectrum disorder, moderate intellectual disability and, epilepsy. Literature review. Epilepsy Res ;2019 (Nov 1) ;158:106223.

INTRODUCTION : Duplication of long arm of chromosome 7(q) is uncommon. It may occur as "pure", isolated anomaly or in association with other mutations involving the same or other chromosomes. "Pure" chromosome 7q duplication has recently been classified by segment involved : the interstitial, proximal, or distal segment of the arm. Attempts to correlate genotype with phenotype in each group has yielded questionable results even though intellective disability and minor dysmorphic features of variable types are typically seen. MATERIAL AND METHODS : In a young boy showing minor facial dysmorphism, language delay, autistic spectrum disorder, epileptic seizures, behavioral disturbances and irritability an array-CGH analysis was carried out. RESULTS : Array-CGH analysis found in the proband a de novo variant of partial duplication of 7q31.32 (122.254.792-122.376.908). DISCUSSION : A very few cases of partial 7q duplication have been reported thus far mainly presenting with clinical signs of dysmorphic features, large head, developmental delay, epileptic seizures and skeletal anomalies. To our knowledge, this is the first report of a case of a de novo variant of 7q31.32 duplication, showing dysmorphic anomalies and neurologic impairment including ASD and seizures. In the 7q31.32 region is located the gene CADPS2, which has been associated to autistic spectrum disorder and other neurologic disorders. In the child, a genotype-phenotype correlation may be hypothesized. Further similar reports may be useful to confirm this observation.

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16. Qiu Z, Yuan B. Towards the Framework of Understanding Autism Spectrum Disorders. Neurosci Bull ;2019 (Nov 9)

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17. Quan L, Yi J, Zhao Y, Zhang F, Shi XT, Feng Z, Miller HL. Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders. Neurotoxicology ;2019 (Nov 5)

OBJECTIVE : The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. METHODS : From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3-8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. RESULTS : In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4-6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0-5.6) mumol/l and 3.0 (2.0-4.4) mumol/l, respectively (P < 0.001). For each 1 mumol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54 ; 95% confidence intervals [CI] : 1.32-1.78 ; P < 0.001) and 27% (1.27 [1.10-1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5-4.9] mumol/l vs. 4.5(3.7-6.0) mumol/l ; P < 0.001). For each 1 mumol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28-2.01], P < 0.001) and 31% (1.31 [1.08-1.49], P < 0.001), respectively. CONCLUSIONS : Elevated plasma levels of TMAO were associated with ASD and symptom severity.

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18. Sledziowska M, Galloway J, Baudouin SJ. Evidence for a Contribution of the Nlgn3/Cyfip1/Fmr1 Pathway in the Pathophysiology of Autism Spectrum Disorders. Neuroscience ;2019 (Nov 6)

Autism Spectrum Disorders (ASD) are characterized by heterogeneity both in their presentation and their genetic aetiology. In order to discover points of convergence common to different cases of ASD, attempts were made to identify the biological pathways genes associated with ASD contribute to. Many of these genes were found to play a role in neuronal and synaptic development and function. Among these genes are FMR1, CYFIP1 and NLGN3, all present at the synapse and reliably linked to ASD. In this review, we evaluate the evidence for the contribution of these genes to the same biological pathway responsible for the regulation of structural and physiological plasticity. Alterations in dendritic spine density and turnover, as well as long-term depression (LTD), were found in mouse models of mutations of all three genes. This overlap in the phenotypes associated with these mouse models likely arises from the molecular interaction between the protein products of FMR1, CYFIP1, and NLG3. A number of other proteins linked to ASD are also likely to participate in these pathways, resulting in further downstream effects. Overall, a synaptic pathway centered around FMR1, CYFIP1, and NLG3 is likely to contribute to the phenotypes associated with structural and physiological plasticity characteristic of ASD.

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19. Waltes R, Freitag CM, Herlt T, Lempp T, Seitz C, Palmason H, Meyer J, Chiocchetti AG. Impact of autism-associated genetic variants in interaction with environmental factors on ADHD comorbidities : an exploratory pilot study. J Neural Transm (Vienna) ;2019 (Nov 9)

Attention-deficit/hyperactivity disorder (ADHD) is determined by genetic and environmental factors, and shares genetic risk with ASD. Functional single-nucleotide polymorphisms of the metabotropic glutamatergic signaling pathway are reported to increase the risk for ASD. The aim of this pilot study was to explore the main effects of respective ASD variants as well as their interaction effects with well-replicated ADHD environmental risk factors on the risk for ADHD, ADHD symptom severities, and comorbidities. We included 318 children with ADHD, aged 5-13 years, and their parents (N = 164 trios, N = 113 duos, N = 41 singletons). Interaction of ASD risk variants CYFIP1-rs7170637, CYFIP1-rs3693, CAMK4-rs25925, and GRM1-rs6923492 with prenatal biological and lifetime psychosocial risk factors was explored in a subsample with complete environmental risk factors (N = 139 trios, N = 83 duos, two singletons) by transmission disequilibrium test and stepwise regression analyses. We identified nominally significant (alpha < 0.05) GxE interactions of acute life events with CYFIP1-rs3693 on ADHD diagnosis (p = 0.004 ; fdr = 0.096) but no significant association of any single marker. Further results suggest that the risk for comorbid disruptive disorders was significantly modulated by GxE interactions between familial risk factors and CAMK4-rs25925 (p = 0.001 ; fdr = 0.018) and prenatal alcohol exposure with CYFIP1-rs3693 (p = 0.003 ; fdr = 0.027) ; both findings survived correction for multiple testing (fdr value < 0.05). Nominal significant GxE interactions moderating the risk for anxiety disorders have also been identified, but did not pass multiple testing corrections. This pilot study suggests that common ASD variants of the glutamatergic system interact with prenatal and lifetime psychosocial risk factors influencing the risk for ADHD common comorbidities and thus warrants replication in larger samples.

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20. Whalon K, Henning B, Jackson E, Intepe-Tingir S. Effects of an adapted story grammar intervention on the listening comprehension of children with autism. Res Dev Disabil ;2019 (Dec) ;95:103507.

Children with autism spectrum disorder (ASD) often develop the word reading skills necessary to read text but struggle with reading comprehension. Comprehension skills are often under addressed in early elementary settings leaving children with ASD at a disadvantage once they are expected to read for meaning. This study investigated the impact of an adapted story grammar intervention on the listening comprehension of five children with ASD in kindergarten through second grade. The intervention embedded evidence-based practices shown to support the learning of children with ASD during story grammar instruction. All participating children demonstrated increased correct responding to fact and inference questions following intervention. Data suggest that all participants required visuals to participate in and learn from the intervention. Social validity data indicate the classroom teacher perceived the intervention as helpful and feasible. Implications for instruction and future research are discussed.

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21. Yang X, Liu Y, Zhou T, Zhang H, Dong R, Li Y, Liu N, Gai Z. An induced pluripotent stem cells line (SDQLCHi014-A) derived from urine cells of a patient with ASD and hyperactivity carrying a 303kb de novo deletion at chr3p26.1 implicating GRM7 gene. Stem Cell Res ;2019 (Nov 2) ;41:101635.

Autism spectrum disorder (ASD) is a childhood-onset neurodevelopmental disorder challenged in social reciprocity and restrictive repetitive behaviors. Here, we generated an induced pluripotent stem cell (iPSC) line SDQLCHi014-A from a patient with ASD and hyperactivity, carrying a 303kb de novo deletion at chr3p26.1 implicating GRM7 gene by reprogramming urine cells with non-integrating vectors. SDQLCHi014-A have shown full pluripotency, differentiation capacity and genetic stability. This iPSC line provides a valuable resource to study the molecular mechanisms underlying ASD.

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Formation à l'état des connaissances de l'autisme {JPEG}


4-Accéder au Livret Autisme Auvergne Rhône-Alpes (LAARA)

Prenez connaissance du Livret Autisme Auvergne Rhône-Alpes, projet de répertoire régional des structures médico-sociales. En cliquant sur l’image ci-dessous :

Cliquer pour accéder au LAARA