Pubmed du 27/11/19

mercredi 27 novembre 2019

1. Barokova M, Tager-Flusberg H. Person-reference in autism spectrum disorder : Developmental trends and the role of linguistic input. Autism research : official journal of the International Society for Autism Research ;2019:10.1002/aur.2243.

Past research has provided mixed evidence of the nature and difficulty with personal pronouns of children with autism spectrum disorder. No study to date has examined the nature of person-reference in autism, more broadly, by looking at referential language both in terms of who is being referred to (self vs. other) and how (words with shifting reference : personal pronouns, vs. fixed reference : names and nouns). Furthermore, the role of linguistic input specifically in the domain of referential language in autism has not been investigated before. We collected natural language samples from parent-child interactions from children with autism (N = 38 ; 7 female) at three time points (age 2, 3, and 4 years) and administered a battery of standardized assessments to evaluate their language ability. The samples were transcribed and coded for person-referential language. Children with autism used increasingly more pronouns both when referring to themselves and to their parent, but pronoun reversals were extremely rare. Their person-reference use was associated with language ability only at age 2. Parental input was also characterized by an increase in pronoun use but only when referring to their child. Parents’ and children’s person-reference were not associated across time, but they were concurrently related at age 3. Autism Res 2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : In this study, we found that as children with autism grew older, they used more and more personal pronouns to refer both to themselves and their parents. Furthermore, they very rarely reversed their pronouns (used I instead of you) with only 1 child out of 38 making a pronoun error. This lack of pronoun errors suggests that pronoun difficulty in autism might not occur for long periods of time throughout development and might not be as prevalent in autism as previously thought.

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2. Berkovits LD, Moody CT, Blacher J. "I don’t feel different. But then again, I wouldn’t know what it feels like to be normal" : Perspectives of Adolescents with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders ;2019:10.1007/s10803-10019-04309-10801.

There is minimal research regarding the personal experiences and perceptions of youth with autism spectrum disorder (ASD). Yet, the positive and negative perceptions that youth internalize about their diagnoses are crucial, as they may have a strong impact on individuals’ self-concept and well-being. This paper utilizes mixed methods to describe the perceptions of 38 adolescents with ASD about their diagnoses, as elicited via semi-structured interviews. Quantitative analyses explore links between youths’ perceptions and other aspects of their social-emotional well-being. Implications are highlighted regarding the importance of shifting the narrative that individuals with ASD develop about themselves and their diagnoses.

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3. Bishop-Fitzpatrick L, Rubenstein E. The Physical and Mental Health of Middle Aged and Older Adults on the Autism Spectrum and the Impact of Intellectual Disability. Research in Autism Spectrum Disorders ;2019 ;63:34-41.

BACKGROUND : People on the autism spectrum may have more physical and mental health conditions in midlife and old age compared to the general population. This study describes the physical and mental health of a unique sample of all middle aged and older Wisconsin Medicaid beneficiaries with an autism spectrum disorder diagnosis and tests differences between those with and without co-occurring intellectual disability. METHOD : Using de-identified Medicaid claims data for 143 adults with a recorded autism spectrum disorder diagnosis aged 40-88 years with any Wisconsin Medicaid claims in 2012 through 2015, we extracted diagnoses for physical and mental health conditions from fee-for-service claims. Logistic regression analyses-controlling for sex, race, and age-compared the adjusted odds of physical and mental health conditions for those with and without intellectual disability. RESULTS : Many physical and mental health conditions, including immune conditions (70.6%), cardiovascular disease (49.0%) and its risk factors (46.2%), sleep disorders (85.3%), gastrointestinal disorders (49.7%), neurologic conditions (55.9%), and psychiatric disorders (72.0%) were highly prevalent in our full sample. Although there were many similarities between those individuals with and without co-occurring intellectual disability, middle aged and older adults on the autism spectrum had higher prevalence of epilepsy and lower prevalence of depression and anxiety compared to those without co-occurring intellectual disability. CONCLUSIONS : Findings suggest that people on the autism spectrum have a high prevalence of physical and mental health conditions in midlife and old age, regardless of intellectual disability status.

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4. Hand BN, Angell AM, Harris L, Carpenter LA. Prevalence of physical and mental health conditions in Medicare-enrolled, autistic older adults. Autism : the international journal of research and practice ;2019:1362361319890793-1362361319890793.

While there is emerging evidence on the prevalence of physical and mental health conditions among autistic adults, less is known about this population’s needs during older adulthood (aged 65+). We conducted a cross-sectional retrospective cohort study of 2016-2017 Medicare data to compare the prevalence of physical and mental health conditions in a national sample of autistic older adults (N = 4685) to a matched population comparison (N = 46,850) cohort. Autistic older adults had significantly greater odds of nearly all physical health conditions including epilepsy (odds ratio = 18.9 ; 95% confidence interval = 17.2-20.7), Parkinson’s disease (odds ratio = 6.1 ; 95% confidence interval = 5.3-7.0), and gastrointestinal conditions (odds ratio = 5.2 ; 95% confidence interval = 4.9-5.5). Most mental health conditions were more common among autistic older adults, including schizophrenia and psychotic disorders (odds ratio = 25.3 ; 95% confidence interval = 22.4-28.7), attention deficit disorders (odds ratio = 24.4 ; 95% confidence interval = 16.2-31.0), personality disorders (odds ratio = 24.1 ; 95% confidence interval = 17.8-32.5), and suicidality or self-inflicted injury (odds ratio = 11.1 ; 95% confidence interval = 8.9-13.8). Health conditions commonly associated with advanced age in the general population (e.g. osteoporosis, cognitive disorders, heart disease, cancer, cerebrovascular disease, osteoarthritis) were also significantly more common among autistic older adults. By highlighting the significant physical and mental health needs for which autistic older adults require care, our findings can inform healthcare systems, healthcare providers, and public health initiatives seeking to promote well-being in this growing population.

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5. Houghton R, de Vries F, Loss G. Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder. CNS drugs ;2019:10.1007/s40263-40019-00686-40264.

BACKGROUND : Psychostimulants and atomoxetine have been shown to increase blood pressure, heart rate, and QT interval in children and adolescents ; however, based on current literature, it is unclear if these "attention-deficit/hyperactivity disorder (ADHD) medications" are also associated with serious cardiovascular (SCV) events. We addressed this question in commonly exposed groups of children and adolescents with either ADHD or autism spectrum disorder (ASD). METHODS : Using commercial (years 2000-2016) and Medicaid (years 2012-2016) administrative claims data from the United States (US), we conducted two case-control studies, nested within respective cohorts of ADHD and ASD children aged 3-18 years. We defined cases by a composite outcome of stroke, myocardial infarction, or serious cardiac arrhythmia. For each case, we matched ten controls on age, sex, and insurance type. We conducted conditional logistic regression models to test associations between SCV outcomes and a primary exposure definition of current ADHD medication use. Additionally, we controlled for resource use, cardiovascular and psychiatric comorbidities, and use of medications in a variety of sensitivity analyses. RESULTS : We identified 2,240,774 children for the ADHD cohort and 326,221 children for the ASD cohort. For ADHD, 33.9% of cases (63 of 186) versus 32.2% of controls (598 of 1860) were exposed, which yielded an odds ratio (OR) and 95% confidence interval (CI) of 1.08 (0.78-1.49). For ASD, 12.5% of cases (6 of 48) versus 22.1% of controls (106 of 480) were exposed [OR 0.49 (0.20-1.20)]. Covariate-adjusted results and results for individual outcomes and other exposure definitions were consistent with no increased risk of SCV events. CONCLUSION : Using large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications.

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6. Kirby AV, Schneider M, Diener M, Henderson J. "Who Is Going to Pay for the Wi-Fi ?" Exploring Adulthood from the Perspectives of Autistic Youth. Autism in adulthood : challenges and management ;2019 ;1(1):37-43.

BACKGROUND : The transition to adulthood involves achievement of objective milestones, yet becoming an adult is also widely considered a subjective experience. Much of the extant research about autistic adulthood focuses on the objective aspects of adulthood, with little emphasis on the subjective experience of adulthood. There is lack of research incorporating the perspectives of autistic youth about preparation for becoming an adult. METHODS : Using semi-structured interviews with 27 autistic adolescents (12-17 years old), we examined youth considerations for adulthood. In a subset of the sample (n=8), we also examined youth perspectives on adulthood in general. The research team conducted qualitative thematic analysis with an inductive, iterative approach. RESULTS : Adolescents considered a variety of factors when considering their plans and desires for adulthood, including their family connections, their own interests and abilities, characteristics of their future situations, and chronological progressions. When speaking about adulthood in general, participants discussed the importance of factors such as age/accomplishment and responsibility/maturity. CONCLUSIONS : This study confirms the appropriateness and importance of conversations with autistic youth about their own adult futures. Understanding how autistic youth understand and consider adulthood can help inform the development of improved supports and services during the transition to adulthood, and promote positive adulthood experiences.

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7. Knowland VCP, Fletcher F, Henderson L-M, Walker S, Norbury CF, Gaskell MG. Sleep Promotes Phonological Learning in Children Across Language and Autism Spectra. Journal of speech, language, and hearing research : JSLHR ;2019:1-21.

Purpose Establishing stable and flexible phonological representations is a key component of language development and 1 which is thought to vary across children with neurodevelopmental disorders affecting language acquisition. Sleep is understood to support the learning and generalization of new phonological mappings in adults, but this remains to be examined in children. This study therefore explored the time course of phonological learning in childhood and how it varies by structural language and autism symptomatology. Method Seventy-seven 7- to 13-year-old children, 30 with high autism symptomatology, were included in the study ; structural language ability varied across the sample. Children learned new phonological mappings based on synthesized speech tokens in the morning ; performance was then charted via repetition (without feedback) over 24 hr and followed up 4 weeks later. On the night following learning, children’s sleep was monitored with polysomnography. Results A period of sleep but not wake was associated with improvement on the phonological learning task in childhood. Sleep was associated with improved performance for both trained items and novel items. Structural language ability predicted overall task performance, though language ability did not predict degree of change from 1 session to the next. By contrast, autism symptomatology did not explain task performance. With respect to sleep architecture, rapid eye movement features were associated with greater phonological generalization. Conclusions Children’s sleep was associated with improvement in performance on both trained and novel items. Phonological generalization was associated with brain activity during rapid eye movement sleep. This study furthers our understanding of individual differences in the acquisition of new phonological mappings and the role of sleep in this process over childhood. Supplemental Material

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8. Kohli-Lynch M, Tann CJ, Ellis ME. Early Intervention for Children at High Risk of Developmental Disability in Low- and Middle-Income Countries : A Narrative Review. International journal of environmental research and public health ;2019 ;16(22):E4449.

In low- and middle-income countries (LMICs), while neonatal mortality has fallen, the number of children under five with developmental disability remains unchanged. The first thousand days are a critical window for brain development, when interventions are particularly effective. Early Childhood Interventions (ECI) are supported by scientific, human rights, human capital and programmatic rationales. In high-income countries, it is recommended that ECI for high-risk infants start in the neonatal period, and specialised interventions for children with developmental disabilities as early as three months of age ; more data is needed on the timing of ECI in LMICs. Emerging evidence supports community-based ECI which focus on peer support, responsive caregiving and preventing secondary morbidities. A combination of individual home visits and community-based groups are likely the best strategy for the delivery of ECI, but more evidence is needed to form strong recommendations, particularly on the dosage of interventions. More data on content, impact and implementation of ECI in LMICs for high-risk infants are urgently needed. The development of ECI for high-risk groups will build on universal early child development best practice but will likely require tailoring to local contexts.

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9. Lomas Mevers J, Call NA, Gerencser KR, Scheithauer M, Miller SJ, Muething C, Hewett S, McCracken C, Scahill L, McElhanon BO. A Pilot Randomized Clinical Trial of a Multidisciplinary Intervention for Encopresis in Children with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders ;2019:10.1007/s10803-10019-04305-10805.

Children with autism spectrum disorder (ASD) are often delayed in achieving bowel continence, resulting in negative outcomes. In this pilot trial, 20 children with ASD and encopresis were randomly assigned to multidisciplinary intervention for encopresis (MIE ; n = 10) or a waitlist control group (n = 10). The MIE group was treated for constipation and received a 10-day behavioral intervention that utilized suppositories to produce predictable bowel movements that were reinforced. Caregivers were trained to implement the intervention. Results support the feasibility of clinical trials of MIE, with high enrolment, competition, attendance, and caregiver acceptability. Preliminary outcomes were positive, with six of 10 in the MIE group achieving continence by the end of treatment compared to 0 in the control group (p = 0.005).Registered at ( ; ID : NCT02383732.

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10. Malaguarnera M, Cauli O. Effects of l-Carnitine in Patients with Autism Spectrum Disorders : Review of Clinical Studies. Molecules (Basel, Switzerland) ;2019 ;24(23):E4262.

Carnitine is an amino acid derivative, which plays several important roles in human physiology, in the central nervous system, and for mitochondrial metabolism, in particular. Altered carnitine metabolic routes have been associated with a subgroup of patients with autism spectrum disorders (ASD) and could add to the pathophysiology associated with these disorders. We review the current evidence about the clinical effects of carnitine administration in ASD in both non-syndromic forms and ASD associated with genetic disorders. Two randomized clinical trials and one open-label prospective trial suggest that carnitine administration could be useful for treating symptoms in non-syndromic ASD. The effect of carnitine administration in ASD associated with genetic disorders is not conclusive because of a lack of clinical trials and objectives in ASD evaluation, but beneficial effects have also been reported for other comorbid disorders, such as intellectual disability and muscular strength. Side effects observed with a dose of 200 mg/kg/day consisted of gastro-intestinal symptoms and a strong, heavy skin odor. Doses of about 50-100 mg/kg/day are generally well tolerated. Further clinical trials with the identification of the subgroup of ASD patients that would benefit from carnitine administration are warranted.

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11. Mazon C, Fage C, Consel C, Amestoy A, Hesling I, Bouvard M, Etchegoyhen K, Sauzéon H. Cognitive Mediators of School-Related Socio-Adaptive Behaviors in ASD and Intellectual Disability Pre- and Adolescents : A Pilot-Study in French Special Education Classrooms. Brain sciences ;2019 ;9(12):E334.

The school inclusion of students with autism is still a challenge. To address the cognitive underpinnings of school-related adaptive behaviors, 27 students with autism and 18 students with intellectual and/or severe learning disability, aged from 11 to 17, were recruited. They underwent socio-emotional processing and executive functioning assessments, as well as school-related adaptive behavior and quality of life measurements. Both groups performed equally on socio-emotional and executive assessments, and they reported the same low quality of life. However, students with autism exhibited more limitations than the students with intellectual disabilities on complex school adaptive behaviors (socialization and autonomy) and problem behaviors, but both groups performed equally on more basic adaptive behaviors (school routines, communication). Multiple regression analyses highlighted between-group differences in terms of adaptive functioning profiles, which were linked with different cognitive predictors according to students’ medical conditions. The greater school-related limitations of students with autism were mostly explained by socio-emotional performance, while IQ (intellectual quotient) mostly explained the comparable between-group limitations. The low quality of life of both groups was slightly explained by executive performance. The role of both socio-emotional and executive functioning in students’ adaptive behaviors and quality of life suggests remediation targets for promoting the school inclusion of students with autism.

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12. Satterstrom FK, Walters RK, Singh T, Wigdor EM, Lescai F, Demontis D, Kosmicki JA, Grove J, Stevens C, Bybjerg-Grauholm J, Bækvad-Hansen M, Palmer DS, Maller JB, i P-BC, Nordentoft M, Mors O, Robinson EB, Hougaard DM, Werge TM, Bo Mortensen P, Neale BM, Børglum AD, Daly MJ. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants. Nature neuroscience ;2019:10.1038/s41593-41019-40527-41598.

The exome sequences of approximately 8,000 children with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) and 5,000 controls were analyzed, finding that individuals with ASD and individuals with ADHD had a similar burden of rare protein-truncating variants in evolutionarily constrained genes, both significantly higher than controls. This motivated a combined analysis across ASD and ADHD, identifying microtubule-associated protein 1A (MAP1A) as a new exome-wide significant gene conferring risk for childhood psychiatric disorders.

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13. Tan Y, Sgobio C, Arzberger T, Machleid F, Tang Q, Findeis E, Tost J, Chakroun T, Gao P, Höllerhage M, Bötzel K, Herms J, Höglinger G, Koeglsperger T. Loss of fragile X mental retardation protein precedes Lewy pathology in Parkinson’s disease. Acta neuropathologica ;2019:10.1007/s00401-00019-02099-00405.

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of α-synuclein (α-syn)-containing neuronal protein aggregates. Although the exact mechanism of α-syn-mediated cell death remains elusive, recent research suggests that α-syn-induced alterations in neuronal excitability contribute to cell death in PD. Because the fragile X mental retardation protein (FMRP) controls the expression and function of numerous neuronal genes related to neuronal excitability and synaptic function, we here investigated the role of FMRP in α-syn-associated pathological changes in cell culture and mouse models of PD as well as in post-mortem human brain tissue from PD patients. We found FMRP to be decreased in cultured DA neurons and in the mouse brain in response to α-syn overexpression. FMRP was, furthermore, lost in the SNc of PD patients and in patients with early stages of incidental Lewy body disease (iLBD). Unlike fragile X syndrome (FXS), FMR1 expression in response to α-syn was regulated by a mechanism involving Protein Kinase C (PKC) and cAMP response element-binding protein (CREB). Reminiscent of FXS neurons, α-syn-overexpressing cells exhibited an increase in membrane N-type calcium channels, increased phosphorylation of ERK1/2, eIF4E and S6, increased overall protein synthesis, and increased expression of Matrix Metalloproteinase 9 (MMP9). FMRP affected neuronal function in a PD animal model, because FMRP-KO mice were resistant to the effect of α-syn on striatal dopamine release. In summary, our results thus reveal a new role of FMRP in PD and support the examination of FMRP-regulated genes in PD disease progression.

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14. Tsai T-H, Chen Y-L, Gau SS-F. Relationships between autistic traits, insufficient sleep, and real-world executive functions in children : a mediation analysis of a national epidemiological survey. Psychological Medicine ;2019:1-8.

BACKGROUND : Although the literature documents low executive functions and sleep deficits in individuals with autism spectrum disorder or subclinical autistic traits, no study has simultaneously examined their relationships in the general child population. This study aimed to examine whether autistic traits impacted real-world executive functions through insufficient sleep in a nationally representative sample of children. METHODS : This was a national survey of 6832 primary and secondary school students, aged 8-14 years old, with equal sex distribution (3479 boys, 50.8%). Parents reported their child’s nocturnal sleep duration and the need for sleep to maintain their daytime function and the Social Responsiveness Scale and the Behavior Rating Inventory of Executive Function (BRIEF) for their children’s autistic traits and real-world executive functions, respectively. RESULTS : We found that autistic traits exerted indirect effects on real-world executive functions through sleep deficits, independent of sex, and age. Moreover, such an indirect effect was observed only from restricted and repetitive behaviors to executive functions through sleep deficits, but not in the other components of autistic traits (i.e. social communication and interaction). CONCLUSIONS : Our novel findings underscore the importance of sleep and autistic traits in executive functions and suggest potential mechanisms that may underlie the observed correlational structure among autistic behaviors, sleep deficits, and low executive function performance.

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15. White R, Barreto M, Harrington J, Kapp SK, Hayes J, Russell G. Is disclosing an autism spectrum disorder in school associated with reduced stigmatization ?. Autism : the international journal of research and practice ;2019:1362361319887625-1362361319887625.

Evidence suggests disclosing an autism diagnosis is associated with reduced stigmatization for autistic adults. However, it is unknown whether this is true for autistic adolescents. We used a vignette-and-questionnaire design to study stigmatizing attitudes with adolescents (aged 11-12 and 14-16 years, total N = 250) in a UK school. We investigated the effect of disclosing that a fictional adolescent had an autism diagnosis on stigmatizing attitudes of peers by testing the effect of disclosure of diagnosis on the social and emotional distance pupils wanted to maintain from the autistic adolescent. We also tested the effect of disclosure on peers’ assessment of the adolescent’s responsibility for their own behaviour. We checked to see if the effects were moderated by gender and age-group. Disclosing autism did not affect the social and emotional distance peers wanted to maintain from the autistic adolescent, but was associated with significant reduction in personal responsibility attributed to the adolescent’s behaviour. Boys attributed more personal responsibility to the autistic adolescent than girls, but this gender effect was reduced when autism was disclosed. These findings suggest that disclosing autism to other pupils may be of limited use in reducing stigmatization by peers in UK schools.

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