Pubmed du 05/09/19

jeudi 5 septembre 2019

1. Accardo AL, Bean K, Cook B, Gillies A, Edgington R, Kuder SJ, Bomgardner EM. College Access, Success and Equity for Students on the Autism Spectrum. J Autism Dev Disord. 2019.

College may be considered a gateway to success, yet access to college is limited for young adults with autism. Given the research recommendations to elicit student experiences and to communicate among universities to improve college access, success, and equity, the present study examined the questions : What factors are perceived as pathways to success or barriers to success by college students on the autism spectrum ? What university provided accommodations and/or support services do they prefer ? Participants from four universities completed surveys and semi-structured interviews. Findings from the multi-university study suggest the need to provide transition planning and systematic non-academic social and emotional supports from the start of the college experience as well as specific training for faculty, staff, and peers.

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2. Bellosta P, Soldano A. Dissecting the Genetics of Autism Spectrum Disorders : A Drosophila Perspective. Frontiers in physiology. 2019 ; 10 : 987.

Autism Spectrum Disorder (ASD) is a complex group of multi-factorial developmental disorders that leads to communication and behavioral defects. Genetic alterations have been identified in around 20% of ASD patients and the use of genetic models, such as Drosophila melanogaster, has been of paramount importance in deciphering the significance of these alterations. In fact, many of the ASD associated genes, such as FMR1, Neurexin, Neuroligins and SHANK encode for proteins that have conserved functions in neurons and during synapse development, both in humans and in the fruit fly. Drosophila is a prominent model in neuroscience due to the conserved genetic networks that control neurodevelopmental processes and to the ease of manipulating its genetics. In the present review we will describe recent advances in the field of ASD with a particular focus on the characterization of genes where the use of Drosophila has been fundamental to better understand their function.

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3. Bilder DA, Esplin MS, Coon H, Burghardt P, Clark EAS, Fraser A, Smith KR, Worsham W, Chappelle K, Rayner T, Bakian AV. Correction to : Early Second Trimester Maternal Serum SteroidRelated Biomarkers Associated with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

The original version of the article has been published without funding source information.

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4. DiCriscio AS, Hu Y, Troiani V. Brief Report : Pupillometry, Visual Perception, and ASD Features in a Task-Switching Paradigm. J Autism Dev Disord. 2019.

We assessed the association between dynamic changes in pupil response in the context of visual perception and quantitative measures of the autism phenotype in healthy adults. Using Navon stimuli in a task-switching paradigm, participants were instructed to identify global or local information based on a cue. Multiple pupil response trajectories across conditions were identified. We combined trajectory patterns for global and local conditions and used data-driven methods to identify three distinct pupil trajectory sub-groups. We report higher scores on quantitative measures of autism features in individuals who demonstrated an increased change in pupil diameter across both conditions. Results demonstrate the use of individualized pupil response trajectories in order to quantitatively characterize visual perception associated with the broader autism phenotype (BAP).

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5. Ferreira L, D’Agostini AR, Pichini FDS, Pazini E, Rechia IC, Biaggio EPV. Auditory training in autism spectrum disorder : a case report. CoDAS. 2019 ; 31(4) : e20180212.

This study aimed to measure the effects of a Computer-based Auditory Training Program (CBATP) on an adolescent diagnosed with Autism Spectrum Disorder (ASD) and Central Auditory Processing Disorder (CAPD). This is the case report of a male, 14-year-old adolescent diagnosed with ASD. The individual was submitted to basic audiological evaluation, central auditory processing assessment and hearing electrophysiology (EP), pre- and post-therapeutic intervention. Central auditory processing (CAP) was assessed by means of the following instruments : Time-compressed Speech Test (TCST), Random Gap Detection Test (RGDT), Staggered Spondaic Word Test (SSWT), Frequency (Pitch) Pattern Sequence Test (FPST), and Duration Pattern Test (DPT). The P300 component of the Event-related Potential (ERP) was used in the hearing EP. Pre-intervention assessment of CAP showed changes in the auditory skills of closure, figure-ground and temporal ordering, but normal temporal resolution ability. Post-intervention evaluation of CAP showed improvement in all previously mentioned auditory skills, except for the figure-ground ability, which remained unchanged. Regarding the findings of the hearing EP, a decrease in the latency of the P300 component was observed pre- and post-intervention. This study demonstrated that the use of a CBATP resulted in improvement in the hearing abilities assessed in an adolescent diagnosed with ASD.

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6. Hahn LJ, Brady NC, Versaci T. Communicative Use of Triadic Eye Gaze in Children With Down Syndrome, Autism Spectrum Disorder, and Other Intellectual and Developmental Disabilities. American journal of speech-language pathology. 2019 : 1-14.

Purpose This study examines differences in the communicative use of triadic eye gaze (TEG) during a communicative interaction in 2 neurodevelopmental disorders : Down syndrome (DS) and autism spectrum disorders (ASD), and a 3rd group of varying disabilities associated with intellectual and developmental disabilities (IDDs). Also, the relationship between TEG use and language abilities was explored. Method Participants were 45 children, 15 in each group. The frequency of TEG was coded during a scripted communication assessment when children were between 3 and 6 years of age (37-73 months). Receptive and expressive language was measured using raw scores from the Mullen Scales of Early Learning concurrently between 3 and 6 years and again 2 years later when children were between 5 and 8 years (59-92 months). Results Descriptively, children with DS had a higher frequency of TEG than children with ASD and IDD, but significant differences were only observed between children with DS and ASD. More TEG at Time 1 in children with DS was associated with higher receptive language at Time 1 and higher expressive language at Time 2. For children with ASD, a trend for a positive association between TEG at Time 1 and language abilities at Time 2 was observed. No significant associations were observed for children with IDD. Conclusion Children with DS used TEG significantly more than children with ASD in this sample. Identifying strengths and weaknesses in TEG use is important because providing caregiver training to facilitate TEG can result in increased opportunities to respond with language models and promote language development.

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7. Iakoucheva LM, Muotri AR, Sebat J. Getting to the Cores of Autism. Cell. 2019 ; 178(6) : 1287-98.

The genetic architecture of autism spectrum disorder (ASD) is itself a diverse allelic spectrum that consists of rare de novo or inherited variants in hundreds of genes and common polygenic risk at thousands of loci. ASD susceptibility genes are interconnected at the level of transcriptional and protein networks, and many function as genetic regulators of neurodevelopment or synaptic proteins that regulate neural activity. So that the core underlying neuropathologies can be further elucidated, we emphasize the importance of first defining subtypes of ASD on the basis of the phenotypic signatures of genes in model systems and humans.

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8. Keifer CM, Hauschild KM, Nelson BD, Hajcak G, Lerner MD. Differences in the Late Positive Potential and P300 to Emotional Faces in Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

Despite evidence suggesting differences in early event-related potential (ERP) responses to social emotional stimuli, little is known about later stage ERP contributions to social emotional processing in individuals with autism spectrum disorder (ASD). Adults with and without ASD completed a facial emotion recognition task involving stimuli that varied by emotional intensity while electroencephalograms were recorded. Principal components analysis was used to examine P300 and late positive potential (LPP) modulation by emotional intensity. Results indicated that greater ASD symptomatology evinced heightened P300 to high relative to low intensity faces, then heightened LPP to low relative to high intensity faces. Findings suggest that adults with greater ASD symptomatology may demonstrate a lag in engagement in elaborative processing of low intensity faces.

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9. Lee HY, Vigen C, Zwaigenbaum L, Bryson S, Smith I, Brian J, Watson LR, Crais ER, Turner-Brown L, Reznick JS, Baranek GT. The Performance of the First Year Inventory (FYI) Screening on a Sample of High-Risk 12-Month-Olds Diagnosed with Autism Spectrum Disorder (ASD) at 36 Months. J Autism Dev Disord. 2019.

This study examined the performance of the First Year Inventory (FYI ; version 2.0), a community-normed parent-reported screening instrument, in a high-risk (HR) sample of 12-month-olds with older siblings diagnosed with autism spectrum disorder (ASD). The FYI 2.0 was completed by parents of 86 HR infants and 35 low-risk control infants at age 12 months, followed by clinical diagnosis at 36 months. HR infants later diagnosed with ASD had significantly higher FYI 2.0 risk scores in both the social-communication and sensory-regulatory domains than typically developing infants. New FYI 2.0 cutoff scores for HR sample were explored by evaluating various cutoff options after considering tradeoffs between sensitivity and specificity and sample characteristics.

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10. Leiva-Garcia B, Planells E, Planells Del Pozo P, Molina-Lopez J. Association Between Feeding Problems and Oral Health Status in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

A number of studies have been made of mealtime behavioral problems and food selectivity in patients with autism spectrum disorder (ASD), though not from a multidisciplinary perspective where diet and dental care are investigated in children with ASD. In the present study, the parents of 55 children with ASD and 91 children with typical development (TD) between 6 and 18 years of age completed the Brief Assessment of Mealtime Behavior in Children (BAMBIC) and a food consumption frequency questionnaire. A pediatric dentist performed an oral exploration of the participants according to the criteria of the World Health Organization (WHO). Food rejection and limited food variety were associated to an increased prevalence of malocclusion and altered Community Periodontal Index scores in children with ASD.

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11. Ma L, Herren AW, Espinal G, Randol J, McLaughlin B, Martinez-Cerdeno V, Pessah IN, Hagerman RJ, Hagerman PJ. Composition of the Intranuclear Inclusions of Fragile X-associated Tremor/Ataxia Syndrome. Acta neuropathologica communications. 2019 ; 7(1) : 143.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation repeat expansion (55-200 CGG repeats) in the 5’ noncoding region of the FMR1 gene. Solitary intranuclear inclusions within FXTAS neurons and astrocytes constitute a hallmark of the disorder, yet our understanding of how and why these bodies form is limited. Here, we have discovered that FXTAS inclusions emit a distinct autofluorescence spectrum, which forms the basis of a novel, unbiased method for isolating FXTAS inclusions by preparative fluorescence-activated cell sorting (FACS). Using a combination of autofluorescence-based FACS and liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based proteomics, we have identified more than two hundred proteins that are enriched within the inclusions relative to FXTAS whole nuclei. Whereas no single protein species dominates inclusion composition, highly enriched levels of conjugated small ubiquitin-related modifier 2 (SUMO 2) protein and p62/sequestosome-1 (p62/SQSTM1) protein were found within the inclusions. Many additional proteins involved with RNA binding, protein turnover, and DNA damage repair were enriched within inclusions relative to total nuclear protein. The current analysis has also allowed the first direct detection, through peptide sequencing, of endogenous FMRpolyG peptide, the product of repeat-associated non-ATG (RAN) translation of the FMR1 mRNA. However, this peptide was found only at extremely low levels and not within whole FXTAS nuclear preparations, raising the question whether endogenous RAN products exist at quantities sufficient to contribute to FXTAS pathogenesis. The abundance of the inclusion-associated ubiquitin- and SUMO-based modifiers supports a model for inclusion formation as the result of increased protein loads and elevated oxidative stress leading to maladaptive autophagy. These results highlight the need to further investigate FXTAS pathogenesis in the context of endogenous systems.

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12. Margoni F, Guglielmetti G, Surian L. Brief Report : Young Children with Autism Can Generate Intent-Based Moral Judgments. J Autism Dev Disord. 2019.

Past research suggested that, due to difficulties in mentalistic reasoning, individuals with autism tend to base their moral judgments on the outcome of agents’ actions rather than on agents’ intentions. In a novel task, aimed at reducing the processing demands required to represent intentions and generate a judgment, autistic children were presented with agents that accidentally harmed or attempted but failed to harm others and were asked to judge those agents. Most of the times, children blamed the character who attempted to harm and exculpated the accidental wrongdoer, suggesting that they generated intent-based moral judgments. These findings suggest that processing limitations rather than lack of conceptual competence explain the poor performance reported in previous research on moral judgment in autism.

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13. Parsons JP, Bedford R, Jones EJH, Charman T, Johnson MH, Gliga T. Gaze Following and Attention to Objects in Infants at Familial Risk for ASD. Front Psychol. 2019 ; 10 : 1799.

Reduced gaze following has been associated previously with lower language scores in children with autism spectrum disorder (ASD). Here, we use eye-tracking in a controlled experimental setting to investigate whether gaze following and attention distribution during a word learning task associate with later developmental and clinical outcomes in a population of infants at familial risk for ASD. Fifteen-month-old infants (n = 124 ; n = 101 with familial risk) watched an actress repeatedly gaze toward and label one of two objects present in front of her. We show that infants who later developed ASD followed gaze as frequently as typically developing peers but spent less time engaged with either object. Moreover, more time spent on faces and less on objects was associated with lower concurrent or later verbal abilities, but not with later symptom severity. No outcome group showed evidence for word learning. Thus, atypical distribution of attention rather than poor gaze following is a limiting factor for language development in infants at familial risk for ASD.

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14. Russo A, DiAntonio A. Wnd/DLK Is a Critical Target of FMRP Responsible for Neurodevelopmental and Behavior Defects in the Drosophila Model of Fragile X Syndrome. Cell reports. 2019 ; 28(10) : 2581-93.e5.

Fragile X syndrome (FXS) is the leading heritable cause of intellectual disability and commonly co-occurs with autism spectrum disorder. Silencing of the Fmr1 gene leads to the absence of the protein product, fragile X mental retardation protein (FMRP), which represses translation of many target mRNAs. Excess translation of these targets is one cause of neuronal dysfunction in FXS. Utilizing the Drosophila model of FXS, we identified the mitogen-activated protein kinase kinase kinase (MAP3K) Wallenda/dual leucine zipper kinase (DLK) as a critical target of FMRP. dFMRP binds Wallenda mRNA and is required to limit Wallenda protein levels. In dFmr1 mutants, Wallenda signaling drives defects in synaptic development, neuronal morphology, and behavior. Pharmacological inhibition of Wallenda in larvae suppresses dFmr1 neurodevelopmental phenotypes, while adult administration prevents dFmr1 behavioral defects. We propose that in dFmr1 mutants chronic Wallenda/DLK signaling disrupts nervous system development and function and that inhibition of this kinase cascade might be a candidate therapeutic intervention for the treatment of FXS.

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15. Rylaarsdam L, Guemez-Gamboa A. Genetic Causes and Modifiers of Autism Spectrum Disorder. Frontiers in cellular neuroscience. 2019 ; 13 : 385.

Autism Spectrum Disorder (ASD) is one of the most prevalent neurodevelopmental disorders, affecting an estimated 1 in 59 children. ASD is highly genetically heterogeneous and may be caused by both inheritable and de novo gene variations. In the past decade, hundreds of genes have been identified that contribute to the serious deficits in communication, social cognition, and behavior that patients often experience. However, these only account for 10-20% of ASD cases, and patients with similar pathogenic variants may be diagnosed on very different levels of the spectrum. In this review, we will describe the genetic landscape of ASD and discuss how genetic modifiers such as copy number variation, single nucleotide polymorphisms, and epigenetic alterations likely play a key role in modulating the phenotypic spectrum of ASD patients. We also consider how genetic modifiers can alter convergent signaling pathways and lead to impaired neural circuitry formation. Lastly, we review sex-linked modifiers and clinical implications. Further understanding of these mechanisms is crucial for both comprehending ASD and for developing novel therapies.

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16. Sarber KM, Howard JJM, Dye TJ, Pascoe JE, Simakajornboon N. Sleep-Disordered Breathing in Pediatric Patients With Rett Syndrome. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2019.

STUDY OBJECTIVES : Although respiratory abnormalities occurring during wakefulness are well recognized in patients with Rett syndrome (RS), less has been reported regarding sleep-disordered breathing (SDB) in this population. This study aims to characterize the presenting complaints, types and severity of SDB, and treatment modalities of patients with RS and sleep concerns. METHODS : Retrospective chart review of pediatric patients with RS referred to our academic tertiary care institution from January 2007 to July 2017. RESULTS : Thirteen patients were identified, 11 female (84.6%) ; mean age at polysomnography (PSG) was 10.3 years (standard deviation 4.94). Eleven were white (84.6%), 2 were black (15.4%). The most common presenting symptoms were snoring (10/13, 77%) and witnessed apnea (7/13, 53.8%). On baseline PSG, all patients (100%) exhibited hyperapneas followed by a central apnea during wake. Nine (69.2%) had obstructive sleep apnea (OSA) (obstructive apnea-hypopnea index (oAHI) > 1) ; four had severe OSA (oAHI >/= 10). One had central sleep apnea (central apnea index > 5) and severe OSA. No patients exhibited hypoventilation on baseline PSG. Mean AHI of all patients was 8.77 +/- 8.82 (oAHI 6.51 +/- 6.91) events/h. Mean oxyhemoglobin nadir was 88.52 +/- 5.6%. Treatment modalities included observation : 5 (38%), acetazolamide : 2 (15%), nasal mometasone : 1 (7.7%), adenotonsillectomy : 3 (23.1%), and positive airway pressure : 2 (15%). CONCLUSIONS : Regarding patients with RS referred to the sleep medicine clinic, snoring and witnessed apneas were the most common presenting complaints. In addition to breathing abnormalities during wake, OSA was very common in our cohort. Further studies are needed to examine the pathogenesis of OSA in RS and relationships between disease genotype and respiratory abnormality phenotype.

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17. Singer EV, Shelton AR, Malow BA. Can We Predict Which Children With Autism Will Have Obstructive Sleep Apnea ?. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2019.

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18. Stein Duker LI, Sadie Kim HK, Pomponio A, Mosqueda L, Pfeiffer B. Examining Primary Care Health Encounters for Adults With Autism Spectrum Disorder. Am J Occup Ther. 2019 ; 73(5) : 7305185030p1-p11.

OBJECTIVE : Our objective was to identify perceived barriers and strategies to improve primary care encounters, as reported by adults with autism spectrum disorder (ASD), caregivers of adults with ASD, and primary care providers (PCPs) treating adults with ASD. METHOD : As part of a larger mixed-methods design, adults with ASD, caregivers, and PCPs (N = 78) in Los Angeles and Philadelphia completed surveys examining barriers to care and strategies to improve care. RESULTS : Multiple barriers to care were reported by adults with ASD and caregivers, including communication and sensory challenges. Adults with ASD and caregivers reported minimal use of strategies during primary care visits but indicated that those used were helpful during care. Expert PCPs reported using strategies more frequently than novice PCPs. All respondent groups endorsed that strategies had the potential to improve care in the future for adults with ASD. CONCLUSION : Opportunities exist for occupational therapy collaboration in primary health care and primary care education to improve care for adults with ASD.

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19. Tomkies A, Johnson RF, Shah G, Caraballo M, Evans P, Mitchell RB. Obstructive Sleep Apnea in Children With Autism. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2019.

STUDY OBJECTIVES : To describe the demographic and clinical characteristics of children with autism spectrum disorder (ASD) referred for polysomnography (PSG) and to look for predictors of obstructive sleep apnea (OSA) and severe OSA in these children. METHODS : This is a retrospective case series of children ages 2 to 18 years who underwent PSG between January 2009 and February 2015. Children were excluded if they had major comorbidities, prior tonsillectomy, or missing data. The following information was collected : age, sex, race, height, weight, tonsil size, and prior diagnosis of allergies, asthma, gastroesophageal reflux disease, seizure disorder, developmental delay, cerebral palsy, or attention deficit hyperactivity disorder. Predictors of OSA were evaluated. RESULTS : A total of 45 children were included with a mean (standard deviation [SD]) age of 6.1 years (2.8). The patients were 80% male, 49% Hispanic, 27% African American, 22% Caucasian, and 2.2% other. Of these children 26 (58%) had OSA (apnea-hypopnea index [AHI] > 1 event/h) and 15 (33%) were obese (body mass index, body mass index z-score >/= 95th percentile). The mean (SD) AHI was 7.7 (15.0) events/h (range 1.0-76.6). A total of 9 (20%) had severe OSA (AHI >/= 10 events/h). There were no demographic or clinical predictors of OSA in this group. However, increasing weight served as a predictor of severe OSA and African American or Hispanic children were more likely obese. CONCLUSIONS : The absence of demographic or clinical predictors of OSA supports using general indications for PSG in children with ASD.

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20. Zetler NK, Cermak SA, Engel-Yeger B, Gal E. Somatosensory Discrimination in People With Autism Spectrum Disorder : A Scoping Review. Am J Occup Ther. 2019 ; 73(5) : 7305205010p1-p14.

IMPORTANCE : Sensory symptoms in people with autism spectrum disorder (ASD) are commonly reported by researchers. However, an often overlooked sensory aspect of ASD is sensory discrimination in general, and somatosensory discrimination in particular. OBJECTIVE : To examine what has and what has not yet been learned concerning the somatosensory discrimination abilities of people with ASD and to reveal gaps warranting further research. DESIGN : Scoping review of clinical studies published 1995-2017 located through searches of PsycNET, PubMed, ERIC, and Google Scholar. Inclusion criteria were English-language peer-reviewed studies with (1) participants diagnosed with ASD, (2) a specific somatosensory discrimination measure, and (3) a comparison group. No age or intellectual exclusion criteria were established ; studies were excluded if they were theoretical or descriptive, did not incorporate a control group, focused only on neurology or genetics, or used simple threshold detection measures or somatosensory measures integrated with other measures. The final search yielded 12 comparative articles discussing tactile and proprioceptive discrimination in people with ASD. RESULTS : Overall, most results showed atypical somatosensory discrimination in people with ASD, especially among young children. The relationship between sensory discrimination abilities and other sensory symptoms and ASD symptoms is briefly discussed. CONCLUSIONS AND RELEVANCE : Heterogeneous findings concerning somatosensory discrimination in people with ASD shed light on underlying mechanisms of these disorders and can contribute to improvement of occupational therapy intervention for this population. WHAT THIS ARTICLE ADDS : The occupational therapy evaluation of people with ASD can benefit from addressing somatosensory discrimination and its contribution to other clinical symptoms. This type of assessment can help improve intervention strategies for people with ASD by promoting a focus on the effect of discrimination deficits on daily function.

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