1. Akins MR, Berk-Rauch HE, Kwan KY, Mitchell ME, Shepard KA, Korsak LI, Stackpole EE, Warner-Schmidt JL, Sestan N, Cameron HA, Fallon JR. {{Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains}}. {Hum Mol Genet}. 2017.
Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXG-associated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.
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2. Bent S, Dang K, Widjaja F, Lawton B, Nazneen, Hendren RL. {{Examining Clinics for Children with Autism: The Autism Translating To Treatments (AT3) Study}}. {J Altern Complement Med}. 2017.
OBJECTIVES: Certain clinical providers specialize in providing complementary and integrative medicine (CIM) therapies for children with autism spectrum disorder (ASD). Because many of these providers and their patients/families have reported substantial improvement, the authors developed an online platform to carefully examine these clinical practices. The initial goal was to examine the feasibility of prospective data collection in this setting. The larger goals were to characterize the tests and treatments used in these clinics; examine associations between specific treatments, biomarkers, and improved outcomes; and identify promising treatments for future study. DESIGN: Prospective cohort study. SETTING: Four CIM clinics specializing in treating children with ASD. PATIENTS: Children with ASD age 2-8 years. INTERVENTIONS: The study protocol provided no interventions, but all interventions provided by the CIM clinical providers were recorded. OUTCOME MEASURES: Aberrant Behavior Checklist (ABC); Social Responsiveness Scale (SRS); and instruments that assessed sensory sensitivity, language, gastrointestinal (GI) symptoms, pediatric quality of life, and caregiver strain. RESULTS: Fourteen children were enrolled (mean age, 4.4 years). Over 3 months, the total behavior score (ABC) decreased (improved) from 110.8 to 103.8 (change, -7.0; 95% confidence interval [CI], -27.9 to 13.9), and the total social responsiveness score (SRS) decreased (improved) from 133.8 to 127.2 (change, -6.6; 95% CI, -30.5 to 17.3), but these changes were not statistically significant. Similarly, caregiver strain and pediatric quality of life decreased (improved) but by a nonsignificant amount. More severe GI symptoms and more severe ASD symptoms were associated with lower quality of life (p < 0.001). CONCLUSIONS: Barriers to successful data collection were identified. Despite these challenges, this study could confirm interesting associations between data elements, highlighting the future value of similar systems for improving evidence-based care in this population. Lien vers le texte intégral (Open Access ou abonnement)
3. Chien YL, Wu YY, Chen HI, Tsai WC, Chiu YN, Liu SK, Gau SS. {{The central nervous system patterning gene variants associated with clinical symptom severity of autism spectrum disorders}}. {J Formos Med Assoc}. 2017.
BACKGROUND/PURPOSE: Central nervous system (CNS) patterning genes are recognized as candidate genes for autism spectrum disorders (ASDs) based on neuroimaging and neuropathological evidence. Several genes that regulate CNS development are shown to be associated with ASD. Our previous family-based association study also revealed that a specific haplotype of WNT2 (wingless-type MMTV integration site family member 2) gene was overtransmitted to probands with ASD. Whether the CNS patterning genes moderate the clinical phenotype of ASD is unclear. This study investigated the genetic associations of WNT2, engrailed 2 (EN2), and forkhead box P2 (FOXP2) with the clinical symptom severity. METHODS: The sample included 391 patients (males, 88.3%; mean age+/-standard deviation, 9.5+/-4.4 years) diagnosed with ASDs. Tag single nucleotide polymorphisms (SNPs) of EN2, WNT2, and FOXP2 were genotyped. The single-locus and multilocus markers were tested for association. RESULTS: We found that multilocus markers of WNT2 were associated with stereotyped behaviors whereas the markers of FOXP2 tended to be associated with social deficits. Moreover, an SNP of WNT2 showed a trend to be associated with less inattentive symptoms. CONCLUSIONS: Our findings that WNT2 and FOXP2 may moderate the clinical phenotypes of ASD provide evidence to support the possible universal effect of WNT2 and FOXP2 on neurodevelopmental symptom dimensions. Such findings warrant further validation in other independent samples. TRIAL REGISTRATION: Clinical trial registration identifier: NCT00494754.
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4. Coderre EL, Chernenok M, Gordon B, Ledoux K. {{Linguistic and Non-Linguistic Semantic Processing in Individuals with Autism Spectrum Disorders: An ERP Study}}. {J Autism Dev Disord}. 2017.
Individuals with autism spectrum disorders (ASD) experience difficulties with language, particularly higher-level functions like semantic integration. Yet some studies indicate that semantic processing of non-linguistic stimuli is not impaired, suggesting a language-specific deficit in semantic processing. Using a semantic priming task, we compared event-related potentials (ERPs) in response to lexico-semantic processing (written words) and visuo-semantic processing (pictures) in adults with ASD and adults with typical development (TD). The ASD group showed successful lexico-semantic and visuo-semantic processing, indicated by similar N400 effects between groups for word and picture stimuli. However, differences in N400 latency and topography in word conditions suggested different lexico-semantic processing mechanisms: an expectancy-based strategy for the TD group but a controlled post-lexical integration strategy for the ASD group.
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5. Deschrijver E, Wiersema JR, Brass M. {{Disentangling Neural Sources of the Motor Interference Effect in High Functioning Autism: An EEG-Study}}. {J Autism Dev Disord}. 2017.
The role of imitation in autism spectrum disorder (ASD) is controversial. Researchers have argued that deficient control of self- and other-related motor representations (self-other distinction) might explain imitation difficulties. In a recent EEG study, we showed that control of imitation relies on high-level as well as on low-level cognitive processes. Here, we aimed to further our insights into control of imitation deficits in ASD. We focused on congruency effects in the P3 (high-level), the N190 and the readiness potential (RP; low-level). We predicted smaller congruency effects within the P3 in the ASD group. However, we found differences in the RP and not in the P3-component. Thus, high-level self-other distinction centred on motor actions may be preserved in ASD, while impairments are reflected during motor preparation.
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6. Friedman C. {{Community integration of people with intellectual and developmental disabilities: A national longitudinal analysis}}. {Disabil Health J}. 2017.
BACKGROUND: Medicaid Home and Community Based Services (HCBS) 1915(c) waivers are the largest providers of long-term supports and services (LTSS) for people with intellectual and developmental disabilities (IDD) in the United States. National and longitudinal analyses of HCBS 1915(c) waivers for people with IDD are critical because of changes in the fiscal landscape, the variability produced by states ability to flexibly customize their programs, and the significant changes required by the HCBS final settings rule. OBJECTIVE/HYPOTHESIS: The aim of this study was to determine spending allocations and state priorities for LTSS for people with IDD through Medicaid HCBS waivers over a five-year period (fiscal year 2011 to fiscal year 2015). METHODS: Medicaid HCBS 1915(c) waivers for people with IDD from fiscal year (FY) 2011 to FY 2015 were analyzed to determine total projected spending, unduplicated participants, and average spending per participant across fiscal years and states. Over 10,000 services from the five years were also analyzed to determine service priorities. RESULTS: This longitudinal analysis of HCBS IDD waiver allocation revealed large fluctuation across five years in terms of total participants, total spending, and average spending per participant. Trends also revealed a shifting away from residential habilitation settings towards supports for living in one’s own home. CONCLUSIONS: When revising waivers to meet the Final Settings Rule, states should utilize our findings to determine areas of need and how to best apply limited funding.
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7. Gao L, Cui SS, Han Y, Dai W, Su YY, Zhang X. {{Does Periconceptional Fish Consumption by Parents Affect the Incidence of Autism Spectrum Disorder and Intelligence Deficiency? A Case-control Study in Tianjin, China}}. {Biomed Environ Sci}. 2016; 29(12): 885-92.
OBJECTIVE: This study aimed to explore the association between periconceptional fish consumption by parents and autism spectrum disorder (ASD) and intelligence deficiency (ID). METHODS: A case-control study was conducted through a questionnaire with 108 ASD cases, 79 ID cases, and 108 controls. The ASD and ID cases were students from special educational schools in Tianjin from 2012 to 2014. The age- and sex-matched controls were from a high school, three primary schools, and a kindergarten in Tianjin. Multivariate logistic regression was performed. RESULTS: Paternal habit of eating hairtail before fertilization, maternal preference for fruits during pregnancy, and maternal habit of eating grass carp during pregnancy were preventive factors for ASD. Paternal habit of drinking alcohol before fertilization was a risk factor for ID, whereas maternal preference for fruits during pregnancy and maternal habit of eating crucian carp during pregnancy were protective factors for ID. CONCLUSION: Parental fish consumption is beneficial for the prevention of ASD and ID. Meanwhile, the protective effects of fish consumption on ASD and ID differ. More attention should be paid to the combined effect of other food when eating fish.
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8. Jain P. {{Novel SCN8A mutation in a girl with refractory seizures and autistic features}}. {Neurol India}. 2017; 65(1): 180-1.
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9. Kovac M, Mosner M, Miller S, Hanna EK, Dichter GS. {{Experience Sampling of Positive Affect in Adolescents with Autism: Feasibility and Preliminary Findings}}. {Res Autism Spectr Disord}. 2016; 29-30: 57-65.
BACKGROUND: Experience sampling is a powerful method for obtaining ecologically valid data from research participants in real-world contexts. Given the urgent need for innovative and sensitive outcome measures in autism spectrum disorder (ASD) research, the present study sought to examine the feasibility of using experience sampling of positive affect and behavior in adolescents with ASD. METHOD: Nineteen high functioning adolescents with ASD and 20 sex and age matched controls completed smartphone- and Qualtrics(R) -based experience sampling of positive affect and behavior six times over four days. RESULTS: Adherence was excellent: adolescents with ASD completed 85% of the assessments, compared to 93% in controls, and response rates were not impacted by age or IQ. Groups did not differ in positive affect overall or as a function of activities, nor did groups differ in the proportion of assessments completed during social or nonsocial activities. However, groups did differ in the proportion of assessments completed during preferred activities. CONCLUSIONS: Results suggest that smartphone- and Qualtrics(R) -based experience sampling with high functioning adolescents with ASD is feasible and captures real-world behaviors that would not be possible using laboratory-based measures.
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10. Rotholz DA, Kinsman AM, Lacy KK, Charles J. {{Improving Early Identification and Intervention for Children at Risk for Autism Spectrum Disorder}}. {Pediatrics}. 2017.
OBJECTIVES: To provide an example of a successful, novel statewide effort to increase early identification of young children at risk for autism spectrum disorder (ASD) using a 2-tiered screening process with enhanced quality assessment, interagency policy collaboration and coordination. METHODS: The South Carolina Act Early Team (SCAET) provided focused collaboration among leaders representing state agencies, universities, health care systems, private organizations, and families to improve quality of life for children with ASD. Specific focus was on implementing policy changes and training to result in earlier identification and home-based behavioral intervention for young children at risk for ASD. RESULTS: Policy changes, training, and modified state agency practices were accomplished. Presumptive eligibility, on the basis of a 2-tiered screening process was implemented by BabyNet (South Carolina’s Early Intervention Program) in collaboration with the lead agency for developmental disability services. There was a fivefold increase in children eligible for early intensive behavioral intervention without waiting for a diagnosis of ASD, avoiding long waits for diagnostic evaluations. Only 16 children (2.5%) were later found not to have ASD from a comprehensive evaluation. CONCLUSIONS: Improvements in early identification and intervention are feasible through collaborative policy change. The South Carolina Act Early Team and its key stakeholders committed to improving outcomes for this population used existing tools and methods in new ways to improve early identification of children with ASD and to make available evidence-based intervention services. This example should be replicable in other states with key stakeholders working collaboratively for the benefit of young children with ASD.
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11. U MS, Rauh R. {{What Difference Does It Make? Implicit, Explicit and Complex Social Cognition in Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2017.
We tested social cognition abilities of adolescents with autism spectrum disorders (ASD) and neurotypically developed peers (NTD). A multi-faceted test-battery including facial emotion categorization (FEC), classical false belief tasks (FBT), and complex social cognition (SC), yielded significantly lower accuracy rates for FEC and complex SC tasks in ASD, but no significant differences in performance concerning FBT. A significant correlation between age and performance in a FEC task and in a complex task was found only in ASD. We propose that dynamic and/or fragmented FEC tasks can elicit deficits in implicit processing of facial emotion more efficiently. The difficulties of ASD in solving complex SC tasks can be ascribed to deficits in the acquisition and application of social schemata.
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12. Vasa RA, Mostofsky SH, Ewen JB. {{The Disrupted Connectivity Hypothesis of Autism Spectrum Disorders: Time for the Next Phase in Research}}. {Biol Psychiatry Cogn Neurosci Neuroimaging}. 2016; 1(3): 245-52.
During the past decade, the disrupted connectivity theory has generated considerable interest as a pathophysiological model for autism spectrum disorders (ASD). This theory postulates that deficiencies in the way the brain coordinates and synchronizes activity amongst different regions may account for the clinical symptoms of ASD. This review critically examines the current structural and functional connectivity data in ASD and evaluates unresolved assumptions and gaps in knowledge that limit the interpretation of these data. Collectively, studies very often show group alterations in what are thought of as measures of cerebral connectivity, though the patterns of findings vary considerably. We argue that there are three principle needs in this research agenda. First, further basic research is needed to understand the links between measures commonly used (DTI, fMRI, EEG) and other (histological, computational) levels of analysis. Second, speculated causes of inconsistencies in the literature (age, clinical heterogeneity) demand studies that directly evaluate these interpretations. Finally, the field needs well-specified mechanistic models of altered cerebral communication in ASD whose predictions can be tested on multiple levels of analyses.
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13. Whitehouse AJ. {{Elizabeth Usher Memorial Lecture: Rethinking the clinical pathway for autism spectrum disorder and challenging the status quo}}. {Int J Speech Lang Pathol}. 2017: 1-10.
Autism spectrum disorder (ASD) is typically diagnosed between 2 and 5 years of age, which is currently thought to be the earliest that the behavioural symptoms are able to be identified without ambiguity. A significant problem with this relatively « late » age of diagnosis is that by the time a child has been identified and diagnosed with ASD, many of the best opportunities for therapies to capitalise upon brain plasticity very early in development are not realised. This paper provides an overview of the benefits and drawbacks of the current clinical pathway that places primacy on a diagnostic assessment for triggering the commencement of therapy. The paper then presents an alternative clinical pathway – the identification and provision of therapy to infants at risk of ASD – and provides a critical review of current evidence supporting this model. The aim of the paper is to outline a vision for the future of early identification and intervention of individuals with ASD, and the research goals that need to be addressed to achieve this vision.
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14. You RS, Serniclaes W, Rider D, Chabane N. {{On the nature of the speech perception deficits in children with autism spectrum disorders}}. {Res Dev Disabil}. 2017.
Previous studies have claimed to show deficits in the perception of speech sounds in autism spectrum disorders (ASD). The aim of the current study was to clarify the nature of such deficits. Children with ASD might only exhibit a lesser amount of precision in the perception of phoneme categories (CPR deficit). However, these children might further present an allophonic mode of speech perception, similar to the one evidenced in dyslexia, characterised by enhanced discrimination of acoustic differences within phoneme categories. Allophonic perception usually gives rise to a categorical perception (CP) deficit, characterised by a weaker coherence between discrimination and identification of speech sounds. The perceptual performance of ASD children was compared to that of control children of the same chronological age. Identification and discrimination data were collected for continua of natural vowels, synthetic vowels, and synthetic consonants. Results confirmed that children with ASD exhibit a CPR deficit for the three stimulus continua. These children further exhibited a trend toward allophonic perception that was, however, not accompanied by the usual CP deficit. These findings confirm that the commonly found CPR deficit is also present in ASD. Whether children with ASD also present allophonic perception requires further investigations.
