1. {{The MMR Vaccine Is Not Associated With Risk for Autism}}. {Ann Intern Med};2019 (Mar 5)
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2. Accardo AL, Finnegan EG, Kuder SJ, Bomgardner EM. {{Writing Interventions for Individuals with Autism Spectrum Disorder: A Research Synthesis}}. {J Autism Dev Disord};2019 (Mar 5)
Building on previous research in the area of written expression for individuals with ASD a research synthesis was conducted to identify (1) writing interventions that have been studied and their effect in improving writing skills of individuals with ASD, (2) intervention features that influence the writing skills of learners with ASD, and (3) the quality of the research. A total of 62 participants were represented across the 24 single case design studies meeting inclusion criteria. Nine interventions emerged with a majority focused on self-regulated strategy development. Effective interventions (PND above 70%) are reported, along with the emergent feature of « packages » using co-occurring combinations of visual, motivational, choice, technology, behavioral, peer, auditory, and tactile supports in conjunction with writing interventions.
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3. Brown M, Ashcraft P, Arning E, Bottiglieri T, McClintock W, Giancola F, Lieberman D, Hauser NS, Miller R, Roullet JB, Pearl P, Gibson KM. {{Rett syndrome (MECP2) and succinic semialdehyde dehydrogenase (ALDH5A1) deficiency in a developmentally delayed female}}. {Mol Genet Genomic Med};2019 (Mar 4):e629.
BACKGROUND: We present a patient with Rett syndrome (RTT; MECP2) and autosomal-recessive succinic semialdehyde dehydrogenase deficiency (SSADHD; ALDH5A1 (aldehyde dehydrogenase 5a1 = SSADH), in whom the current phenotype exhibits features of SSADHD (hypotonia, global developmental delay) and RTT (hand stereotypies, gait anomalies). METHODS: gamma-Hydroxybutyric acid (GHB) was quantified by UPLC-tandem mass spectrometry, while mutation analysis followed standard methodology of whole-exome sequencing. RESULTS: The biochemical hallmark of SSADHD, GHB was increased in the proband’s dried bloodspot (DBS; 673 microM; previous SSADHD DBSs (n = 7), range 124-4851 microM); control range (n = 2,831), 0-78 microM. The proband was compound heterozygous for pathogenic ALDH5A1 mutations (p.(Asn418IlefsTer39); maternal; p.(Gly409Asp); paternal) and a de novo RTT nonsense mutation in MECP2 (p.Arg255*). CONCLUSION: The major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), is increased in SSADHD but normal in RTT, although there are likely regional changes in GABA receptor distribution. GABAergic anomalies occur in both disorders, each featuring an autism spectrum phenotype. What effect the SSADHD biochemical anomalies (elevated GABA, GHB) might play in the neurodevelopmental/epileptic phenotype of our patient is currently unknown.
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4. Buxbaum JD, Baron-Cohen S, Anagnostou E, Ashwin C, Betancur C, Chakrabarti B, Crawley JN, Hoekstra RA, Hof PR, Lai MC, Lombardo MV, Schumann CM. {{Rigor in science and science reporting: updated guidelines for submissions to Molecular Autism}}. {Mol Autism};2019;10:6.
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5. Cogne B, Ehresmann S, Beauregard-Lacroix E, Rousseau J, Besnard T, Garcia T, Petrovski S, Avni S, McWalter K, Blackburn PR, Sanders SJ, Uguen K, Harris J, Cohen JS, Blyth M, Lehman A, Berg J, Li MH, Kini U, Joss S, von der Lippe C, Gordon CT, Humberson JB, Robak L, Scott DA, Sutton VR, Skraban CM, Johnston JJ, Poduri A, Nordenskjold M, Shashi V, Gerkes EH, Bongers E, Gilissen C, Zarate YA, Kvarnung M, Lally KP, Kulch PA, Daniels B, Hernandez-Garcia A, Stong N, McGaughran J, Retterer K, Tveten K, Sullivan J, Geisheker MR, Stray-Pedersen A, Tarpinian JM, Klee EW, Sapp JC, Zyskind J, Holla OL, Bedoukian E, Filippini F, Guimier A, Picard A, Busk OL, Punetha J, Pfundt R, Lindstrand A, Nordgren A, Kalb F, Desai M, Ebanks AH, Jhangiani SN, Dewan T, Coban Akdemir ZH, Telegrafi A, Zackai EH, Begtrup A, Song X, Toutain A, Wentzensen IM, Odent S, Bonneau D, Latypova X, Deb W, Redon S, Bilan F, Legendre M, Troyer C, Whitlock K, Caluseriu O, Murphree MI, Pichurin PN, Agre K, Gavrilova R, Rinne T, Park M, Shain C, Heinzen EL, Xiao R, Amiel J, Lyonnet S, Isidor B, Biesecker LG, Lowenstein D, Posey JE, Denomme-Pichon AS, Ferec C, Yang XJ, Rosenfeld JA, Gilbert-Dussardier B, Audebert-Bellanger S, Redon R, Stessman HAF, Nellaker C, Yang Y, Lupski JR, Goldstein DB, Eichler EE, Bolduc F, Bezieau S, Kury S, Campeau PM. {{Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability}}. {Am J Hum Genet};2019 (Mar 7);104(3):530-541.
Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
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6. Dai YG, Miller LE, Ramsey RK, Robins DL, Fein DA, Dumont-Mathieu T. {{Incremental Utility of 24-Month Autism Spectrum Disorder Screening After Negative 18-Month Screening}}. {J Autism Dev Disord};2019 (Mar 4)
The American Academy of Pediatrics recommends Autism Spectrum Disorder (ASD) screening at 18 and 24 months. However, utility of rescreening at 24 months, after a negative 18-month screening, remains unknown. We identified cases of ASD detected at 24 months after a negative 18-month screening (i.e., Catch-24 group; n = 10) and compared them to toddlers detected by 18-month screening (i.e., Early Diagnosis group; n = 203). Repeated ASD-specific screening at 24 months detected children who were missed at their 18-month screening. Thus, our findings support repeated screening for ASD at both 18 and 24 months in order to maximize identification of toddlers with ASD and other neurodevelopmental disorders who require intervention.
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7. Hadad BS, Schwartz S. {{Perception in autism does not adhere to Weber’s law}}. {Elife};2019 (Mar 4);8
Perceptual atypicalities are a widely acknowledged but poorly understood feature of autism. We demonstrate here a striking violation of one of the most adaptive psychophysical computations – Weber’s law – in high-functioning individuals with autism. JNDs based on the best-fitting psychometric functions were measured for size visual judgments (Exp. 1), weight haptic discrimination (Exp. 2), and illusive perception of weight (brightness-weight illusion; Exp. 3). Results for the typically developed group confirmed Weber’s law, demonstrating a linear increase in JNDs with intensity, resulting in constant fractions across intensities. The results for the ASD, in contrast, showed no scaling of JNDs with intensity; instead, fractions decreased linearly with intensity. In striking contrast to its consistency in typical perception, Weber’s law does not hold for visual and haptic perception in autism. These robust modulations in psychophysical computations, demonstrated for different domains of perception, suggest a modality-independent, low-level mechanism driving altered perception in autism.
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8. He AX, Luyster R, Hong SJ, Arunachalam S. {{Personal pronoun usage in maternal input to infants at high vs. low risk for autism spectrum disorder}}. {First Lang};2018 (Oct);38(5):520-537.
Children with autism spectrum disorder (ASD) are prone to personal pronoun difficulties. This paper investigates maternal input as a potential contributing factor, focusing on an early developmental stage before ASD diagnosis. Using Quigley and McNally’s (2013) corpus of maternal speech to infants (3-19 months; N = 19) who are either at high or low risk for a diagnosis of ASD (Quigley & McNally, 2013), we asked whether mothers used fewer pronouns with high-risk infants. Indeed, high-risk infants heard fewer second-person pronouns relative to their names than low-risk infants. We further investigated the contexts in which mothers were using infants’ names. Our results indicated that mothers of high-risk infants often used the infants’ names simply to get their attention by calling them. We suggest that high-risk infants may thus hear relatively fewer pronouns because their mothers spend more time trying to get their attention. This may be related to differences in social-communicative behavior between low-risk and high-risk infants.
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9. Hviid A, Hansen JV, Frisch M, Melbye M. {{Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study}}. {Ann Intern Med};2019 (Mar 5)
Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake. Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination. Design: Nationwide cohort study. Setting: Denmark. Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013. Measurements: Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score). Results: During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100 000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination. Limitation: No individual medical charts were reviewed. Conclusion: The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases. Primary Funding Source: Novo Nordisk Foundation and Danish Ministry of Health.
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10. Newman C, Cashin A, Graham I. {{Identification of service development needs for incarcerated adults with autism spectrum disorders in an Australian prison system}}. {Int J Prison Health};2019 (Mar 11);15(1):24-36.
PURPOSE: The purpose of this paper is to identify and deliberate the service development needs required for the improvement of service provision for incarcerated adults with autism spectrum disorder (ASD) in NSW, Australia. DESIGN/METHODOLOGY/APPROACH: Consultation groups were conducted to bring together n=5 key stakeholders from heath and correctional-based services in the prison system. A facilitated asynchronous e-mail-based discussion occurred amongst group members between consultation group meetings. FINDINGS: Two main themes were identified: detecting persons with ASD and providing appropriate care. Participants discussed current service gaps with regard to the identification of people with ASD at the point of contact with the prison service, and the difficulties associated with diagnosing prisoners with ASD. The need for effective alert systems to detect persons with ASD in custody was identified. The current absence of ASD-specific support services in prison was highlighted, and recommendations for improvement suggested. PRACTICAL IMPLICATIONS: Current health and correctional-based service provision failed to adequately support incarcerated adults with ASD. Improvements in prison-entry screening processes, alert systems and diagnostic practices are required. Multidisciplinary collaboration between prison-based and external service providers is required for the development of a model of care based on individualised case management to adequately support incarcerated adults with ASD in prison. ORIGINALITY/VALUE: Given the lack of reported service provision for incarcerated adults with ASD internationally, other prison-based services are likely to experience similar service development needs and see the relevance of the recommendations made directly from the study findings.
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11. Parikh MN, Li H, He L. {{Enhancing Diagnosis of Autism With Optimized Machine Learning Models and Personal Characteristic Data}}. {Front Comput Neurosci};2019;13:9.
Autism spectrum disorder (ASD) is a developmental disorder, affecting about 1% of the global population. Currently, the only clinical method for diagnosing ASD are standardized ASD tests which require prolonged diagnostic time and increased medical costs. Our objective was to explore the predictive power of personal characteristic data (PCD) from a large well-characterized dataset to improve upon prior diagnostic models of ASD. We extracted six personal characteristics (age, sex, handedness, and three individual measures of IQ) from 851 subjects in the Autism Brain Imaging Data Exchange (ABIDE) database. ABIDE is an international collaborative project that collected data from a large number of ASD patients and typical non-ASD controls from 17 research and clinical institutes. We employed this publicly available database to test nine supervised machine learning models. We implemented a cross-validation strategy to train and test those machine learning models for classification between typical non-ASD controls and ASD patients. We assessed classification performance using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Of the nine models we tested using six personal characteristics, the neural network model performed the best with a mean AUC (SD) of 0.646 (0.005), followed by k-nearest neighbor with a mean AUC (SD) of 0.641 (0.004). This study established an optimal ASD classification performance with PCD as features. With additional discriminative features (e.g., neuroimaging), machine learning models may ultimately enable automated clinical diagnosis of autism.
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12. Richardson L, McCoy A, McNaughton D. {{« He’s worth the extra work »: The employment experiences of adults with ASD who use augmentative and alternative communication (AAC) as reported by adults with ASD, family members, and employers}}. {Work};2019;62(2):205-219.
BACKGROUND: Employment is a key determinant in quality of life. However, less than 50% of adults with ASD are employed. OBJECTIVE: In order to better support community-based employment for persons with ASD who use augmentative and alternative communication (AAC), there is a need to better understand those situations in which successful outcomes have been achieved. METHOD: This study utilized a multiple case design to investigate the experiences of seven individuals with ASD who use AAC and are successfully employed in the community. RESULTS: Results provide evidence that individuals with ASD who use AAC can be successfully employed, when provided with appropriate supports. Expressive and receptive communication were commonly identified as challenges, however, mobile devices provided support to communication and participation for many of the participants with ASD. CONCLUSIONS: Results from the current study provide evidence that successful employment for individuals with ASD who use AAC is possible when intervention addresses three key areas: the development of skills that are valued in the workplace, the identification and creation of good job matches, and access to needed supports.
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13. Sturrock A, Yau N, Freed J, Adams C. {{Speaking the Same Language? A Preliminary Investigation, Comparing the Language and Communication Skills of Females and Males with High-Functioning Autism}}. {J Autism Dev Disord};2019 (Mar 4)
Understanding the nature of language and communication disorders in High-Functioning Autism Spectrum Disorder (HFASD) populations may provide insight into why females are more likely than males to go undiagnosed. Language and communication skills were compared between 13 females and 13 males (aged 8.11-11.06) with HFASD. Gender-normative data was also ascertained from 26 typically developing children (TD) matched for age and gender. All children had typical range PIQ, slight variation here was controlled for in analysis. Results show females outperforming males in pragmatic and semantic tasks and in certain language-of-emotion tasks. TDs outperformed HFASDs in above-sentence level tasks, but not in basic vocabulary or sentence level tasks. This study highlights specific strengths/weaknesses in language and communication for female HFASD, which could aid more accurate identification of the female autistic phenotype. It indicates the need for larger follow up studies in this area.
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14. Turowetz J, Maynard DW. {{Documenting diagnosis: testing, labelling, and the production of medical records in an autism clinic}}. {Sociol Health Illn};2019 (Mar 5)
All diagnosis depends on communication between doctors and patients. This is especially so with behavioural disorders such as autism, where structured interactions involving clinicians and children (e.g. standardised tests) play a key role in diagnosing the condition. Although such interactions are collaborative, we find that when reporting test results, clinicians, following administrative protocols, routinely gloss over the embodied interactions constitutive of testing, such that autism is predicated as an inherent feature of the child. In ethnomethodological terms, this is related to the way that « accounts » (Garfinkel ), including diagnoses, are reflexively related to the taken-for-granted practices that make them objectively reportable in prevailing professional terms. These practices include how the clinicians themselves interact with children they examine, with other professionals, and with the instruments used to test a child. Examining video footage of a multi-stage autism evaluation, along with the medical report rendering the child’s diagnosis, we show how reporting practices, while addressing the administrative features of standardised testing and diagnosis, can also be examined for their grounding in an environment of tacit matters usually unavailable for inspection. We conclude by asking whether, and how, oral and written reports might re-situate children in the concreteness of their social environments.
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15. Uddin LQ. {{Effects of Participant Functioning Level on Brain Functional Connectivity in Autism}}. {Biol Psychiatry Cogn Neurosci Neuroimaging};2019 (Mar);4(3):216-217.
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16. Vershkov D, Fainstein N, Suissa S, Golan-Lev T, Ben-Hur T, Benvenisty N. {{FMR1 Reactivating Treatments in Fragile X iPSC-Derived Neural Progenitors In Vitro and In Vivo}}. {Cell Rep};2019 (Mar 5);26(10):2531-2539 e2534.
Fragile X syndrome (FXS) is caused primarily by a CGG repeat expansion in the FMR1 gene that triggers its transcriptional silencing. In order to investigate the regulatory layers involved in FMR1 inactivation, we tested a collection of chromatin modulators for the ability to reactivate the FMR1 locus. Although inhibitors of DNA methyltransferase (DNMT) induced the highest levels of FMR1 expression, a combination of a DNMT inhibitor and another compound potentiated the effect of reactivating treatment. To better assess the rescue effect following direct demethylation, we characterized the long-term and genome-wide effects of FMR1 reactivation and established an in vivo system to analyze FMR1-reactivating therapies. Systemic treatment with a DNMT inhibitor in mice carrying FXS induced pluripotent stem cell (iPSC)-derived transplants robustly induced FMR1 expression in the affected tissue, which was maintained for a prolonged period of time. Finally, we show a proof of principle for FMR1-reactivating therapy in the context of the CNS.
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17. Young RL, Brewer N. {{Brief Report: Perspective Taking Deficits, Autism Spectrum Disorder, and Allaying Police Officers’ Suspicions About Criminal Involvement}}. {J Autism Dev Disord};2019 (Mar 4)
We examined whether perspective taking (or Theory of Mind) deficits that characterize autistic individuals predict whether they have trouble extricating themselves from situations in which police officers erroneously suspect them of a crime. Autistic and typically developing adults listened to scenarios in which they were placed in situations where the police erroneously believe they had been involved in crime. Each scenario contained critical information that, if recognized and provided to the police, would confirm non-involvement in the crime. Autistic adults performed markedly worse than controls on perspective taking measures and the extrication task. Verbal IQ and memory performance accounted for significant variance in extrication performance, and perspective taking explained an additional and significant 15% of variance in extrication performance.
