Pubmed du 14/02/20

vendredi 14 février 2020

1. Conner CM, White SW, Scahill L, Mazefsky CA. The role of emotion regulation and core autism symptoms in the experience of anxiety in autism. Autism ;2020 (Feb 12):1362361320904217.

LAY ABSTRACT : Many children with autism spectrum disorder have problems with managing their emotions (emotion regulation) and anxiety. In this study, over 1000 parents completed an online survey which showed that emotion regulation and anxiety are closely linked. Although emotion regulation and anxiety are inter-connected, the results also show that autism symptoms play an important role in anxiety in autism spectrum disorder. Emotion regulation problems may be an important target for the treatment of anxiety in autism.

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2. Gao D, Yu T, Li CL, Jia FY, Li HH. [Effect of parental training based on Early Start Denver Model combined with intensive training on children with autism spectrum disorder and its impact on parenting stress]. Zhongguo Dang Dai Er Ke Za Zhi ;2020 (Feb) ;22(2):158-163.

OBJECTIVE : To explore the effect of parental training based on the Early Start Denver Model (ESDM) combined with intensive training on the treatment outcome of children with autism spectrum disorder (ASD) and its impact on parenting stress. METHODS : Seventy children aged 2-5 years who were diagnosed with ASD were enrolled in the study. They were divided into an ESDM group and a parental training group by the random number table method (n=35 each). The ESDM group received intensive training based on ESDM. In addition to intensive ESDM-based training, parents of the children in the parental training group received ESDM skills training. Both groups were assessed by Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC) and Parenting Stress Index-Short Form (PSI-SF) before and after the intervention of 3 months. RESULTS : After 3 months of intervention, the total scores of ABC, CARS and ATEC were both significantly decreased in the two groups (P<0.05). There was no significant difference in the total scores of ABC, CARS and ATEC between the two groups before and after intervention (P>0.05). The change between ABC, CARS and ATEC total scores in the two groups had no significant difference (P>0.05). After 3 months of intervention, the total scores of PSI-SF were both significantly decreased in the two groups (P<0.05). The difficult child sub-scale scores in PSI-SF were significantly decreased in the ESDM group (P<0.05). While three sub-scale scores of parent distress, parent-child dysfunctional interaction and difficult child in PSI-SF were significantly decreased in the parental training group (P<0.05). Before and after intervention of 3 months, no significant difference was found in PSI-SF total scores between the two groups. Compared with the ESDM group, the change between PSI-SF total scores and two sub-scales of PSI-SF (parent distress and difficult child) were significantly bigger in the parental training group (P<0.05). CONCLUSIONS : Both the combination of intensive training and parent training based on ESDM and ESDM intensive training alone can improve the core symptoms of children with ASD aged 2-5 years and relieve the parenting stress, however, the former is more effective in relieving parenting stress.

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3. Gil-Hernandez F, Gomez-Fernandez AR, la Torre-Aguilar MJ, Perez-Navero JL, Flores-Rojas K, Martin-Borreguero P, Gil-Campos M. Neurotoxicity by mercury is not associated with autism spectrum disorders in Spanish children. Ital J Pediatr ;2020 (Feb 12) ;46(1):19.

BACKGROUND : The pathophysiological etiologies related with the development of Autism Spectrum Disorders (ASD) remain controversial. Different authors have studied neurotoxins such as mercury (Hg) and their relationship with ADS. The objective of this study was to assess the levels of Hg in hair in a group of ASD children (chronic exposure) and in urinary excretion (acute exposure), in comparison to a healthy group. METHODS : A case-control study was conducted in Spanish children. We compared 54 ASD children (aged 2-6) with no other associated pathology to a normally-developing control group (54 subjects). RESULTS : There were no differences in urine (p:0.631) and hair (p:1.000) samples percentages below the limits of detection between the control and the ASD groups, and also between patients in the regression ASD subgroup (AMR) (p:0.08) and the non-regression ASD subgroup (ANMR) (p:0.705). When the analysis was adjusted for age and sex, the differences between Hg levels maintained not significant. There were no correlations between Hg concentrations in the ASD group as a whole (p : 0.739), or when they were subdivided into ASD-AMR (p : 0.739) and ASD-ANMR (p : 0.363). CONCLUSIONS : The present study shows no evidence in our geographical area to support an association between mercury neurotoxicity and the etiopathogenesis of ASD.

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4. Griesi-Oliveira K, Fogo MS, Pinto BGG, Alves AY, Suzuki AM, Morales AG, Ezquina S, Sosa OJ, Sutton GJ, Sunaga-Franze DY, Bueno AP, Seabra G, Sardinha L, Costa SS, Rosenberg C, Zachi EC, Sertie AL, Martins-de-Souza D, Reis EM, Voineagu I, Passos-Bueno MR. Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder. Mol Psychiatry ;2020 (Feb 14)

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target.

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5. Hall DA, Robertson EE, Leehey M, McAsey A, Ouyang B, Berry-Kravis E, O’Keefe JA. Open-label pilot clinical trial of citicoline for fragile X-associated tremor/ataxia syndrome (FXTAS). PLoS One ;2020 ;15(2):e0225191.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that is characterized by tremor, cerebellar ataxia, frequent falls, cognitive decline, and progressive loss of motor function. There are currently no approved treatments for this disorder. The purpose of this study was to determine if citicoline was safe for the treatment of tremor and balance abnormalities and to stabilize cognitive decline in patients with FXTAS. Ten participants with diagnosed FXTAS were administered 1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was the FXTAS Rating Scale score. Secondary outcomes included change in a battery of neuropsychological tests, an instrumented Timed up and go test, computerized dynamic posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom questionnaires. Safety was also evaluated. Citicoline treatment resulted in minimal adverse events in all but one subject over the course of the study. There was a significant improvement in the Beck Anxiety Inventory (p = 0.03) and the Stroop Color-Word test (p = 0.03), with all other measures remaining stable over the course of 12 months. This open-label pilot trial of citicoline for individuals with FXTAS showed that it is safe and well tolerated in this population. Registration : This trial was registered at Identifier : NCT0219710.

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6. Hillier A, Ryan J, Buckingham A, Schena D, 2nd, Queenan A, Dottolo A, Abreu M. Prospective College Students With Autism Spectrum Disorder : Parent Perspectives. Psychol Rep ;2020 (Feb 14):33294120905517.

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7. Horwitz EH, Schoevers RA, Greaves-Lord K, de Bildt A, Hartman CA. Adult Manifestation of Milder Forms of Autism Spectrum Disorder ; Autistic and Non-autistic Psychopathology. J Autism Dev Disord ;2020 (Feb 12)

We compared the presence of autistic and comorbid psychopathology and functional impairments in young adults who received a clinical diagnosis of Pervasive Developmental Disorders Not Otherwise Specified or Asperger’s Disorder during childhood to that of a referred comparison group. While the Autism Spectrum Disorder group on average scored higher on a dimensional ASD self- and other-report measure than clinical controls, the majority did not exceed the ASD cutoff according to the Autism Diagnostic Observation Schedule. Part of the individuals with an ASD diagnosis in their youth no longer show behaviors that underscribe a clinical ASD diagnosis in adulthood, but have subtle difficulties in social functioning and a vulnerability for a range of other psychiatric disorders.

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8. Kuno-Fujita A, Iwabuchi T, Wakusawa K, Ito H, Suzuki K, Shigetomi A, Hirotaka K, Tsujii M, Tsuchiya KJ. Sensory Processing Patterns and Fusiform Activity During Face Processing in Autism Spectrum Disorder. Autism Res ;2020 (Feb 14)

A growing body of evidence has indicated that individuals with autism spectrum disorder (ASD) exhibit abnormal reactions to sensory stimuli and impaired face processing. Although behavioral studies have reported that individual differences in sensory processing patterns are correlated with performance in face processing tasks, the neural substrates underlying the association between sensory processing patterns and face processing remain unknown. Using functional magnetic resonance imaging, the present study examined the relationships between sensory processing patterns assessed with the Adolescent/Adult Sensory Profile (AASP) and brain activity during a one-back task with two types of stimuli (face or house pictures). We enrolled 18 Japanese adults with ASD and 19 age- and IQ-matched controls. Sensation Avoiding scores, which were assessed using the AASP, were positively correlated with right fusiform activity during the presentation of pictures of faces in the ASD group, but not in the control group. This suggests that abnormal sensory processing patterns in ASD are associated with abnormal face-related brain activity, possibly resulting in impaired face processing. LAY SUMMARY : Sensory abnormalities are one of the most common symptoms in people with autism spectrum disorder (ASD). This study shows that individuals with ASD who react abnormally to sensory stimuli also exhibit atypical brain activity when recognizing faces. Abnormal sensory processing may partly explain the difficulty that people diagnosed with ASD have in identifying others’ faces.

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9. Livingston LA, Shah P, Milner V, Happe F. Quantifying compensatory strategies in adults with and without diagnosed autism. Mol Autism ;2020 (Feb 12) ;11(1):15.

BACKGROUND : There is growing recognition that some autistic people engage in ’compensation’, showing few behavioural symptoms (e.g. neurotypical social skills), despite continuing to experience autism-related cognitive difficulties (e.g. difficulties in social cognition). One way this might be achieved is by individuals consciously employing ’compensatory strategies’ during everyday social interaction. However, very little is currently known about the broad range of these strategies, their mechanisms and consequences for clinical presentation and diagnosis. METHODS : We aimed to measure compensatory strategies in autism for the first time. Using a novel checklist, we quantified self-reported social compensatory strategies in 117 adults (58 with autism, 59 without autism) and explored the relationships between compensation scores and autism diagnostic status, autistic traits, education level, sex and age at diagnosis. RESULTS : Higher compensation scores-representing a greater repertoire of compensatory strategies-were associated with having an autism diagnosis, more autistic traits and a higher education level. The link between autism diagnostic status and compensation scores was, however, explained by autistic traits and education level. Compensation scores were unrelated to sex or age at diagnosis. LIMITATIONS : Our sample was self-selected and predominantly comprised of intellectually able females ; therefore, our findings may not generalise to the wider autistic population. CONCLUSIONS : Together, our findings suggest that many intellectually able adults, with and without a clinical diagnosis of autism, report using compensatory strategies to modify their social behaviour. We discuss the clinical utility of measuring self-reported compensation (e.g., using our checklist), with important implications for the accurate diagnosis and management of autism and related conditions.

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10. Luo CW, Deng XY, Cheng JL, Xiao DX, Zhang CY, Feng JX, Chen SQ, Hu N. Altered anxiety and social behaviors in a mouse model of Fragile X syndrome treated with hyperbaric oxygen therapy. J Clin Neurosci ;2020 (Feb 14)

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

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11. Maras K, Norris JE, Brewer N. Metacognitive Monitoring and Control of Eyewitness Memory Reports in Autism. Autism Res ;2020 (Feb 13)

Providing eyewitness testimony involves monitoring one’s memory to provide a detailed and accurate account : reporting details likely to be accurate and withholding potentially inaccurate details. Autistic individuals reportedly experience difficulties in both retrieving episodic memories and monitoring their accuracy, which has important implications for eyewitness testimony. Thirty autistic and 33 IQ-matched typically developing (TD) participants viewed a video of a mock bank robbery followed by three phases of questions (with judgments of confidence). In Phase 1, participants freely generated the granularity of their responses (i.e., fine- or coarse-grained). In Phase 2, participants answered the same questions but provided both a fine- and a coarse-grained answer. In Phase 3, participants were instructed to maximize accuracy over informativeness by selecting one of their Phase 2 answers as their final answer. They either received the questions socially (from the experimenter) or answered them online. There were no group differences in accuracy or metacognitive monitoring, with both autistic and TD witnesses demonstrating : (a) a strong preference for reporting fine-grained details at the expense of accuracy ; (b) improved though still suboptimal grain size reporting when instructed to maximize accuracy over informativeness ; (c) effective accuracy monitoring ; and (d) higher overall accuracy when questions were delivered socially. There was, however, a subtle difference in metacognitive control, with autistic witnesses performing more poorly than TD witnesses when questions were delivered socially, but not when they were delivered online. These findings contrast with evidence suggesting that autism is marked by impairments in episodic memory and metacognitive monitoring and control. LAY SUMMARY : Autistic people have been reported to experience subtle difficulties in monitoring and regulating their information reporting, which has important implications for providing eyewitness testimony. We found that autistic witnesses’ testimony comprised a similar level of detail and accuracy as non-autistic witnesses’ accounts. However, autistic people found it difficult to optimize their testimony when the questions were delivered socially-but not when they answered the questions online. (c) 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.

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12. McDaniel J, Yoder P, Crandall M, Millan ME, Ardel CM, Gengoux GW, Hardan AY. Effects of pivotal response treatment on reciprocal vocal contingency in a randomized controlled trial of children with autism spectrum disorder. Autism ;2020 (Feb 14):1362361320903138.

LAY ABSTRACT : A recent randomized controlled trial found that children with autism spectrum disorder who received a pivotal response treatment package showed improved language and social communication skills following the intervention. The pivotal response treatment package includes clinician-delivered and parent-implemented strategies. Reciprocal vocal contingency is an automated measure of vocal reciprocity derived from daylong audio samples from the child’s natural environment. It may provide stronger and complementary evidence of the effects of the pivotal response treatment package because it is at lower risk for detection bias than parent report and brief parent-child interaction measures. The current study compared reciprocal vocal contingency for 24 children with autism spectrum disorder in the pivotal response treatment package group and 24 children with autism spectrum disorder in the control group. The pivotal response treatment package group received 24 weeks of the pivotal response treatment package intervention. The control group received their usual intervention services during that time. The groups did not differ in reciprocal vocal contingency when the intervention started or after 12 weeks of intervention. However, after 24 weeks the pivotal response treatment package group had higher ranked reciprocal vocal contingency scores than the control group. These findings are consistent with results from parent report and parent-child interaction measures obtained during the trial. The participants in the pivotal response treatment package exhibited greater vocal responsiveness to adult vocal responses to their vocalizations than the control group. Findings support the effectiveness of the pivotal response treatment package on vocal reciprocity of children with autism spectrum disorder, which may be a pivotal skill for language development.

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13. Nerli E, Roggero OM, Baj G, Tongiorgi E. In vitro modeling of dendritic atrophy in Rett syndrome : determinants for phenotypic drug screening in neurodevelopmental disorders. Sci Rep ;2020 (Feb 12) ;10(1):2491.

Dendritic atrophy, defined as the reduction in complexity of the neuronal arborization, is a hallmark of several neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, affecting 1:10,000 girls worldwide, is mainly caused by mutations in the MECP2 gene and has no cure. We describe here an in vitro model of dendritic atrophy in Mecp2(-/y) mouse hippocampal primary cultures, suitable for phenotypic drug-screening. Using High-Content Imaging techniques, we systematically investigated the impact of culturing determinants on several parameters such as neuronal survival, total dendritic length, dendritic endpoints, soma size, cell clusterization, spontaneous activity. Determinants included cell-seeding density, glass or polystyrene substrates, coating with poly-Ornithine with/without Matrigel and miniaturization from 24 to 96-half surface multiwell plates. We show that in all plate-sizes at densities below 320 cells/mm(2), morphological parameters remained constant while spontaneous network activity decreased according to the cell-density. Mecp2(-/y) neurons cultured at 160 cells/mm(2) density in 96 multiwell plates, displayed significant dendritic atrophy and showed a marked increase in dendritic length following treatment with Brain-derived neurotrophic factor (BDNF) or Mirtazapine. In conclusion, we have established a phenotypic assay suitable for fast screening of hundreds of compounds, which may be extended to other neurodevelopmental diseases with dendritic atrophy.

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14. Ocanto R, Levi-Minzi MA, Chung J, Sheehan T, Padilla O, Brimlow D. The development and implementation of a training program for pediatric dentistry residents working with patients diagnosed with ASD in a special needs dental clinic. J Dent Educ ;2020 (Feb 13)

Oral health care is the most prevalent unmet health care need among all U.S. children age 17 and under in the U.S., and this includes those with special health care needs (SHCN). Children with SHCN experience unique barriers to receiving oral care including challenging behaviors, inadequate insurance coverage, and a lack of trained dentists. Despite the need for specialized training to successfully provide dental care to children with SHCN, few dental programs offer the necessary educational preparation. The Nova Southeastern University College of Dentistry was funded by the Health Resources and Services Administration to prepare pediatric and Advanced Education in General Dentistry (AEGD) dental residents in the care of children, adolescents, and adults with SHCN. The purpose of this paper is to describe the didactic and clinical training program and to provide data on the program’s impact.

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15. Ribeiro DM, Miguel CF. Using multiple-tact training to produce emergent visual categorization in children with autism. J Appl Behav Anal ;2020 (Feb 14)

Previous research has shown that children with autism spectrum disorder (ASD) can categorize visual stimuli without direct training when they can also tact these stimuli using a common name and behave as listeners in relation to this name. However, children usually learn to assign objects specific names prior to learning the category to which they belong. The current study replicated previous research and evaluated whether multiple-tact training would establish visual categorization (measured by a picture sorting test) and listener behavior. We used a nonconcurrent multiple baseline design across 2 children with autism spectrum disorder. After multiple-tact training, we assessed whether participants would visually categorize stimuli based on their common category name. Both participants categorized and engaged in the corresponding listener behavior.

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16. Rimmer A. Health secretary is threatened with legal action over treatment of people with learning disabilities and autism. Bmj ;2020 (Feb 12) ;368:m578.

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17. Sheppard E, Mitchell P, Alkhaldi RS. How are Autistic People Perceived ? A Reply to Chown, Hughes and Baker-Rogers (2019). J Autism Dev Disord ;2020 (Feb 12)

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18. Soltys SM, Scherbel JR, Kurian JR, Diebold T, Wilson T, Hedden L, Groesch K, Diaz-Sylvester PL, Botchway A, Campbell P, Loret de Mola JR. An association of intrapartum synthetic oxytocin dosing and the odds of developing autism. Autism ;2020 (Feb 14):1362361320902903.

LAY ABSTRACT : Oxytocin is a hormone naturally produced in the human body that can make the womb (uterus) contract during labor. Manufactured oxytocin is frequently given to mothers in labor to strengthen the contractions or in some cases to start labor. This study compared children with a diagnosis of autism and children without autism to see whether children with autism received more oxytocin during labor. The odds of a child having an autism diagnosis were significantly higher if the delivery was a first-time Cesarean section, if the mother had a body mass index of 35 or higher, or if the reason for delivery were a range of fetal problems that made delivery necessary. It was found that boys who were exposed to oxytocin for longer periods of time during labor and received higher total doses of oxytocin had significantly higher odds of developing autism. There were no significant associations of oxytocin dosing and autism noted in female children. As this is the first study to look at any relationship between the dose of oxytocin received during labor and the odds of developing autism, further study needs to be done to determine whether there is any cause and effect relationship. Thus, at this time, there is no recommended change in clinical practice.

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19. Suhumaran S, Yeleswarapu SP, Daniel LM, Wong CM. Congenital blindness and autism spectrum disorder (ASD) : diagnostic challenges and intervention options. BMJ Case Rep ;2020 (Feb 11) ;13(2)

The case of a 6-year-old boy with congenital blindness and features suggestive of autism spectrum disorder (ASD) is reported. He presented to a developmental paediatrician with global developmental delay, worsening self-injurious behaviours and difficulties in social interaction, transitions and interactive play. He demonstrated poor response to his name, rigidity, repetitive behaviours and had a sensory profile suggestive of ASD. This paper discusses the challenges in diagnosing and managing ASD in visually impaired children.

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20. Wicks R, Paynter J, Westerveld MF. Looking or talking : Visual attention and verbal engagement during shared book reading of preschool children on the autism spectrum. Autism ;2020 (Feb 12):1362361319900594.

LAY ABSTRACT : Children who have an autism diagnosis often have trouble learning to talk and read. These difficulties become noticeable before children start school and may be linked to lower attention and engagement in literacy-related activities such as sharing storybooks with their parents. To date, few researchers have looked at possible ways to measure how children on the autism spectrum engage during shared storybook reading, for example, where children look or how much they talk, and how this may be related to their letter-name knowledge and their vocabulary knowledge. In this study, we analyzed videos of 40 preschoolers on the spectrum and their parents sharing an unfamiliar storybook. We wanted to see whether where children looked (i.e. toward the storybook, their parent, or elsewhere) and how much they talked were related to what their parents did (e.g. ask questions or provide prompts) and/or children’s letter-name knowledge and vocabulary. The videos were coded for different child and parent behaviors. We found that where children looked and how much they talked were strongly related to each other and what parents did during the shared book reading interaction, particularly asking questions and using prompts. In contrast to what we expected, where children looked was not related to children’s letter or vocabulary knowledge. Overall, results of the study draw attention to the connection between what parents do and what preschoolers on the spectrum do when sharing storybooks and provide directions for future research.

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21. Williams Buckley A, Hirtz D, Oskoui M, Armstrong MJ, Batra A, Bridgemohan C, Coury D, Dawson G, Donley D, Findling RL, Gaughan T, Gloss D, Gronseth G, Kessler R, Merillat S, Michelson D, Owens J, Pringsheim T, Sikich L, Stahmer A, Thurm A, Tuchman R, Warren Z, Wetherby A, Wiznitzer M, Ashwal S. Practice guideline : Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder : Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology ;2020 (Feb 12)

OBJECTIVE : To review pharmacologic and nonpharmacologic strategies for treating sleep disturbances in children and adolescents with autism spectrum disorder (ASD) and to develop recommendations for addressing sleep disturbance in this population. METHODS : The guideline panel followed the American Academy of Neurology 2011 guideline development process, as amended. The systematic review included studies through December 2017. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS LEVEL B : For children and adolescents with ASD and sleep disturbance, clinicians should assess for medications and coexisting conditions that could contribute to the sleep disturbance and should address identified issues. Clinicians should counsel parents regarding strategies for improved sleep habits with behavioral strategies as a first-line treatment approach for sleep disturbance either alone or in combination with pharmacologic or nutraceutical approaches. Clinicians should offer melatonin if behavioral strategies have not been helpful and contributing coexisting conditions and use of concomitant medications have been addressed, starting with a low dose. Clinicians should recommend using pharmaceutical-grade melatonin if available. Clinicians should counsel children, adolescents, and parents regarding potential adverse effects of melatonin use and the lack of long-term safety data. Clinicians should counsel that there is currently no evidence to support the routine use of weighted blankets or specialized mattress technology for improving disrupted sleep. If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals.

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