Pubmed du 18/10/19

vendredi 18 octobre 2019

1. Al-Batayneh OB, Nazer TS, Khader YS, Owais AI. Effectiveness of a tooth-brushing programme using the picture exchange communication system (PECS) on gingival health of children with autism spectrum disorders. Eur Arch Paediatr Dent ;2019 (Oct 18)

PURPOSE : The Picture Exchange Communication System (PECS) is a communication system for children with autism spectrum disorders (ASD). The aim of this study was to assess the effect of a PECS-based tooth-brushing programme on gingival health in children with ASD and assess parents’ perception of PECS. METHODS : This was a prospective interventional study. Using PECS as a pictures/cards series showing a structured tooth-brushing method, 37 children with ASD (31 males, 6 females) (average age 9.49 +/- 4.10, 4-16 years) and their parents/caregivers were trained on tooth-brushing twice, 2 weeks apart. Data collected after examinations (baseline, 3, 6-months) included gingival and plaque indices (GI, PI) and two questionnaires (baseline, 6-months) for demographic data and parents’ perception of PECS including difficulty rating (easy, hard, very hard) and PECS usefulness. RESULTS : Most children with ASD had language abilities (64.9%) and prior PECS use (67.6%). Both GI and PI significantly dropped between baseline and both re-evaluations, (P < 0.001). Age, among studied factors, significantly affected PI only at all stages (P < 0.001). Most parents/caregivers (75.7%) rated PECS as hard, but useful (100%). Age and PECS prior use significantly affected PECS difficulty rating (P = 0.000 and 0.031, respectively), while sex did not (P > 0.05). CONCLUSION : PECS though rated as hard was useful in improving gingival health in children with ASD.

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2. Araujo DJ, Tjoa K, Saijo K. The Endocannabinoid System as a Window Into Microglial Biology and Its Relationship to Autism. Front Cell Neurosci ;2019 ;13:424.

Microglia are the resident, innate immune cells of the central nervous system (CNS) and are critical in managing CNS injuries and infections. Microglia also maintain CNS homeostasis by influencing neuronal development, viability, and function. However, aberrant microglial activity and phenotypes are associated with CNS pathology, including autism spectrum disorder (ASD). Thus, improving our knowledge of microglial regulation could provide insights into the maintenance of CNS homeostasis as well as the prevention and treatment of ASD. Control of microglial activity is in part overseen by small, lipid-derived molecules known as endogenous cannabinoids (endocannabinoids). Endocannabinoids are one component of the endocannabinoid system (ECS), which also includes the enzymes that metabolize these ligands, in addition to cannabinoid receptor 1 (CB1) and 2 (CB2). Interestingly, increased ECS signaling leads to an anti-inflammatory, neuroprotective phenotype in microglia. Here, we review the literature and propose that ECS signaling represents a largely untapped area for understanding microglial biology and its relationship to ASD, with special attention paid to issues surrounding the use of recreational cannabis (marijuana). We also discuss major questions within the field and suggest directions for future research.

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3. Doll CA, Yergert KM, Appel BH. The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth. Glia ;2019 (Oct 18)

During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with myelin. The highly polarized oligodendrocytes generate myelin sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote myelin sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for myelin sheath development, we examined fmr1(-/-) mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1(-/-) mutants developed myelin sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential myelin protein, was reduced in myelin tracts of fmr1(-/-) mutants, but loss of FMRP function did not impact the localization of mbpa transcript in myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1(-/-) mutant sheath growth and induced short myelin sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes sheath growth through local regulation of translation.

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4. Hoffmann A, Krause SE, Wuu J, Leurgans S, Guter SJ, Jr., Block SS, Salt J, Cook E, Jr., Maino DM, Berry-Kravis E. Vocabulary comprehension in adults with fragile X syndrome (FXS). J Neurodev Disord ;2019 (Oct 16) ;11(1):25.

BACKGROUND : Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age ; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS : This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS : Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS : Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential.

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5. Hollingdale J, Woodhouse E, Young S, Fridman A, Mandy W. Autistic Spectrum Disorder symptoms in children and adolescents with Attention-deficit/hyperactivity disorder : a meta-analytical review - Corrigendum. Psychol Med ;2019 (Oct 18):1.

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6. Hooijer AAT, Sizoo BB. Temperament and Character as Risk Factor for Suicide Ideation and Attempts in Adults with Autism Spectrum Disorders. Autism Res ;2019 (Oct 17)

Persons with autism spectrum disorders (ASDs) are suggested to have an increased risk for suicide ideation and suicide attempts, but this topic is largely understudied. Research indicates that temperament and character traits are associated with suicidal behavior in persons without ASD, with higher scores for novelty seeking (NS), harm avoidance (HA), and self-transcedence (ST), and lower scores for self-directedness (SD) and cooperativeness (CO). Usually persons with ASD have temperament and character profiles with high HA, and low NS, reward dependence (RD), SD, and CO. The aim is to investigate whether there is a relationship between temperament and character traits and suicide ideation and attempts in adults with ASD. Seventy-four adults with ASD participated by completing self-report measures on suicide thoughts and behavior, depression, and temperament. Independent sample t-tests were conducted to compare scores between attempters versus nonattempters and between ideators versus nonideators. Regression analysis was performed to explore the predictive value of temperament and character. T-tests showed lower NS and SD, and higher HA for ideators versus nonideators, but not for attempters versus nonattempters. Regression models showed no significant relation between suicide ideation and NS, SD, HA after the latter were controlled for the significant influence of depression. Temperament and character can probably not be used for predicting suicide ideation and attempts, based on results from the current sample. Clinicians must take note of the high prevalence and risk of depression among persons with ASD, which may be under-reported. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The aim of the current study was to uncover risk factors for suicide ideation and attempts in adults with autism, since this urgent topic is largely understudied. We initially investigated whether temperament and character could be risk factors, but found no association. However, we did find that depression might be a high predictor for suicide ideation, which could remain under-reported in adults with autism, due to impaired communication and problems with expressing emotions and thoughts.

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7. Kadam SD, Sullivan BJ, Goyal A, Blue ME, Smith-Hicks C. Rett Syndrome and CDKL5 Deficiency Disorder : From Bench to Clinic. Int J Mol Sci ;2019 (Oct 15) ;20(20)

Rett syndrome (RTT) and CDKL5 deficiency disorder (CDD) are two rare X-linked developmental brain disorders with overlapping but distinct phenotypic features. This review examines the impact of loss of methyl-CpG-binding protein 2 (MeCP2) and cyclin-dependent kinase-like 5 (CDKL5) on clinical phenotype, deficits in synaptic- and circuit-homeostatic mechanisms, seizures, and sleep. In particular, we compare the overlapping and contrasting features between RTT and CDD in clinic and in preclinical studies. Finally, we discuss lessons learned from recent clinical trials while reviewing the findings from pre-clinical studies.

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8. Lee GT, Hu X, Liu Y, Zou C, Cheng X, Zhao Q, Huang J. Increasing Response Diversity to Intraverbals in Children with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Oct 16)

The purpose of this study was to evaluate the effects of intraverbal prompts on response diversity and novelty in intraverbals posed to children with autism spectrum disorder (ASD). The intraverbal prompts involving function, feature, and class (FFC) of an item were used in the training of three questions requiring multiple responses. Two Chinese boys with ASD (aged 5-6 years) served as participants. A multiple-probe across three behaviors design was employed. The results indicated that the intraverbal prompts effectively increased the number of divergent responses to all three questions. Novel responses emerged at a low level while generalization to similar questions was not observed following the training.

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9. Licari MK, Alvares GA, Varcin K, Evans KL, Cleary D, Reid SL, Glasson EJ, Bebbington K, Reynolds JE, Wray J, Whitehouse AJO. Prevalence of Motor Difficulties in Autism Spectrum Disorder : Analysis of a Population-Based Cohort. Autism Res ;2019 (Oct 18)

Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged </=6 years (N = 2,084 ; 81.2% males, 18.8% females). Prevalence of motor difficulties was quantified based on scores from the motor domain of the Vineland and then compared to other domains of functioning within the Vineland (communication, daily living, and socialization), the DSM criteria, intellectual level, age, and gender. Scores on the Vineland indicated that 35.4% of the sample met criteria for motor difficulties (standard score <70), a rate almost as common as intellectual impairment (37.7%). Motor difficulties were reported by diagnosing clinicians in only 1.34% of cases. Motor difficulties were common in those cases meeting diagnostic criteria for impairments in nonverbal behavior and the presence of restricted and repetitive behaviors. The prevalence of motor difficulties also increased with increasing age of diagnosis (P < 0.001). Findings from the present study highlight the need for further consideration of motor difficulties as a distinct specifier within the diagnostic criteria for ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : In this population-based cohort that included 2,084 children with autism aged </=6 years, over one-third met the criteria for motor difficulties, a rate almost as common as intellectual disability. This study demonstrates that motor difficulties are a prominent feature of the autism phenotype requiring further consideration in both the diagnostic criteria and evaluation of autism.

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10. Muit JJ, Bothof N, Kan CC. Pharmacotherapy of ADHD in Adults With Autism Spectrum Disorder : Effectiveness and Side Effects. J Atten Disord ;2019 (Oct 18):1087054719866255.

Objective : Symptoms of ADHD are expected to be more difficult to treat in patients with a combination of ADHD and autism spectrum disorder (ASD) as opposed to only ADHD. Little evidence is available on the influence of ASD on the effects of pharmacotherapy in adults with ADHD. This study addresses this gap. Method : 60 adults with ADHD and comorbid ASD were selected from an outpatient clinic and compared with 226 adults from the same clinic with only ADHD. Similar treatment regimens were received. Results : Significant decreases in symptoms of ADHD were found in both groups. A diagnosis of ASD did not affect the reduction in symptoms of ADHD. No significant group differences in side effects or vital signs were found. Conclusion : Results show that medication for ADHD can effectively and safely be prescribed to patients with ADHD and comorbid ASD. Suggestions for future research are discussed.

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11. Nazim A, Khalid R. Assessment of temperament in children with autism spectrum disorders. J Pak Med Assoc ;2019 (Oct) ;69(10):1437-1441.

OBJECTIVE : To explore the temperament and its correlates in children with autism spectrum disorders. METHODS : The cross-sectional study was conducted in Lahore, Pakistan, from February 2015 to June 2016, and comprised children aged 5-11 years diagnosed with autism spectrum disorders selected from different institutes. A detailed demographic questionnaire, Temperament in Middle Childhood questionnaire and Childhood Behaviour questionnaire were administered through in-depth clinical interviews to collect information regarding temperament and significant demographic variables of the subjects. RESULTS : Of the 92 subjects, there were 61(66%) boys and 31(34%) girls. Overall mean age was 8.621.87 years. The girls had relatively high scores on negative affectivity 19.54 5.14 (d=0.14) than boys. Whereas, boys scored comparatively higher on surgency 15.816.80 (d=0.21) and effortful control 13.693.72 (d=0.31) domains of temperament than girls. Negative affectivity shared significant inverse association with cognitive functioning r= - 0.35 (p=0.01). However, surgency r =0.17 and effortful control domains r =0.34 (p=0.01)were positively associated with intellectual functioning. CONCLUSIONS : Children with autism spectrum disorders showed a temperament profile different from children following typical development.

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12. Nimmo-Smith V, Heuvelman H, Dalman C, Lundberg M, Idring S, Carpenter P, Magnusson C, Rai D. Anxiety Disorders in Adults with Autism Spectrum Disorder : A Population-Based Study. J Autism Dev Disord ;2019 (Oct 16)

Anxiety is common in children with ASD ; however, the burden of specific anxiety disorders for adults with ASD is under-researched. Using the Stockholm Youth Cohort, we compared anxiety disorder diagnoses among autistic adults (n = 4049), with or without intellectual disability, and population controls (n = 217,645). We conducted additional sibling analyses. Anxiety disorders were diagnosed in 20.1% of adults with ASD compared with 8.7% of controls (RR = 2.62 [95% CI 2.47-2.79]), with greatest risk for autistic people without intellectual disability. Rates of almost all individual anxiety disorders were raised, notably obsessive-compulsive disorder and phobic anxiety disorders. Anxiety disorders were more common in full siblings and half-siblings of people with ASD. The implications of this are explored.

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13. Pan YH, Wu N, Yuan XB. Toward a Better Understanding of Neuronal Migration Deficits in Autism Spectrum Disorders. Front Cell Dev Biol ;2019 ;7:205.

Newborn neurons in developing brains actively migrate from germinal zones to designated regions before being wired into functional circuits. The motility and trajectory of migrating neurons are regulated by both extracellular factors and intracellular signaling cascades. Defects in the molecular machinery of neuronal migration lead to mis-localization of affected neurons and are considered as an important etiology of multiple developmental disorders including epilepsy, dyslexia, schizophrenia (SCZ), and autism spectrum disorders (ASD). However, the mechanisms that link neuronal migration deficits to the development of these diseases remain elusive. This review focuses on neuronal migration deficits in ASD. From a translational perspective, we discuss (1) whether neuronal migration deficits are general neuropathological characteristics of ASD ; (2) how the phenotypic heterogeneity of neuronal migration disorders is generated ; (3) how neuronal migration deficits lead to functional defects of brain circuits ; and (4) how therapeutic intervention of neuronal migration deficits can be a potential treatment for ASD.

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14. Quintin EM. Music-Evoked Reward and Emotion : Relative Strengths and Response to Intervention of People With ASD. Front Neural Circuits ;2019 ;13:49.

This review presents research findings showing that music is a unique domain to assess perception, reward, emotion, and associated physiological reactions and neural circuitry of people with autism spectrum disorder (ASD). There is growing evidence, reported in several studies in this review article, indicating that music is a relative strength of people with ASD including musical pitch perception, musical memory, and identification of music-evoked emotions. Listening to music activates neural circuits of reward and emotion response, which are described. Research presented shows adults with ASD also activate these systems when listening to music, although there may be developmental differences in the physiological and neural response to music in childhood and adolescence alongside typical behavioral response. Nonetheless, studies reviewed lend support to the use of music therapy and education for people with ASD, specifically to improve social skills and communication. Neural correlates of response to music therapy and education are also discussed. Taken together, findings reviewed provide evidence for music as a strength-based approach for ASD to assess reward and emotion response and as a powerful tool for intervention.

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15. Rahman M, Arevalo F, Coelho A, Bilgili E. Hybrid Nanocrystal-Amorphous Solid Dispersions (HyNASDs) as Alternative to ASDs for Enhanced Release of BCS Class II Drugs. Eur J Pharm Biopharm ;2019 (Oct 14)

A major shortcoming of drug nanocomposites as compared with amorphous solid dispersions (ASDs) is their limited supersaturation capability in dissolution media. Here, we prepared drug hybrid nanocrystal-amorphous solid dispersions (HyNASDs) and compare their performance to ASDs. A wet-milled griseofulvin (GF, BCS II drug) nanosuspension and a GF solution, both containing the same dissolved polymer-surfactant (SDS : sodium dodecyl sulfate) with 1:1 and 1:3 GF:polymer mass ratios, were spray-dried. Hydroxypropyl cellulose (HPC) and Soluplus (Sol) were used as matrix-forming polymers. XRPD, DSC, and Raman spectroscopy reveal that ASDs were formed upon spray-drying the solution-based feed, whereas nanocomposites and nanocomposites with >10% amorphous content, HyNASDs, were formed with the nanosuspension-based feed. Sol provided higher GF relative supersaturation, up to 180% and 360% for HyNASDs and ASDs, respectively, in the dissolution tests than HPC (up to 50% for both) owing to Sol’s stronger intermolecular interactions and miscibility with GF and its recrystallization inhibition. Besides the higher kinetic solubility of GF in Sol, presence of GF nanoparticles vs. micron-sized particles in the nanocomposites enabled fast supersaturation. This study demonstrates successful preparation of fast supersaturating (190% within 20 min) HyNASDs, which renders nanoparticle formulations competitive to ASDs in bioavailability enhancement of poorly soluble drugs.

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16. Rose V, Paynter J, Vivanti G, Keen D, Trembath D. Predictors of Expressive Language Change for Children with Autism Spectrum Disorder Receiving AAC-Infused Comprehensive Intervention. J Autism Dev Disord ;2019 (Oct 16)

Comprehensive interventions for children with autism spectrum disorder (ASD) often incorporate augmentative and alternative communication (AAC) ; however, variability in outcomes exists even among children who access similar intervention. This study investigated predictors of expressive language change for 48 children with ASD aged 31 to 67 months receiving AAC-infused intervention. The relationships between participants’ initial responses to AAC and expressive language change were examined. Commonly reported predictors (IQ, chronological age, ASD symptomatology) did not significantly predict expressive language change. AAC factors (visual attention, object play, word learning) entered at Step 2 of a hierarchical multiple regression, explained an additional 42% of the variance. The findings provide preliminary data on child characteristics associated with expressive language changes within AAC-infused comprehensive interventions.

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17. Sceniak MP, Fedder KN, Wang Q, Droubi S, Babcock K, Patwardhan S, Wright-Zornes J, Pham L, Sabo SL. An autism-associated mutation in GluN2B prevents NMDA receptor trafficking and interferes with dendrite growth. J Cell Sci ;2019 (Oct 18) ;132(20)

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with multiple genetic associations. Analysis of de novo mutations identified GRIN2B, which encodes the GluN2B subunit of NMDA receptors, as a gene linked to ASDs with high probability. However, the mechanisms by which GRIN2B mutations contribute to ASD pathophysiology are not understood. Here, we investigated the cellular phenotypes induced by a human mutation that is predicted to truncate GluN2B within the extracellular loop. This mutation abolished NMDA-dependent Ca(2+) influx. Mutant GluN2B co-assembled with GluN1 but was not trafficked to the cell surface or dendrites. When mutant GluN2B was expressed in developing cortical neurons, dendrites appeared underdeveloped, with shorter and fewer branches, while spine density was unaffected. Mutant dendritic arbors were often dysmorphic, displaying abnormal filopodial-like structures. Interestingly, dendrite maldevelopment appeared when mutant GluN2B was expressed on a wild-type background, reflecting the disease given that individuals are heterozygous for GRIN2B mutations. Restoring the fourth transmembrane domain and cytoplasmic tail did not rescue the phenotypes. Finally, abnormal development was not accompanied by reduced mTOR signaling. These data suggest that mutations in GluN2B contribute to ASD pathogenesis by disrupting dendrite development.

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18. Venker CE, Pomper R, Mahr T, Edwards J, Saffran J, Ellis Weismer S. Comparing Automatic Eye Tracking and Manual Gaze Coding Methods in Young Children with Autism Spectrum Disorder. Autism Res ;2019 (Oct 17)

Eye-gaze methods offer numerous advantages for studying cognitive processes in children with autism spectrum disorder (ASD), but data loss may threaten the validity and generalizability of results. Some eye-gaze systems may be more vulnerable to data loss than others, but to our knowledge, this issue has not been empirically investigated. In the current study, we asked whether automatic eye-tracking and manual gaze coding produce different rates of data loss or different results in a group of 51 toddlers with ASD. Data from both systems were gathered (from the same children) simultaneously, during the same experimental sessions. As predicted, manual gaze coding produced significantly less data loss than automatic eye tracking, as indicated by the number of usable trials and the proportion of looks to the images per trial. In addition, automatic eye-tracking and manual gaze coding produced different patterns of results, suggesting that the eye-gaze system used to address a particular research question could alter a study’s findings and the scientific conclusions that follow. It is our hope that the information from this and future methodological studies will help researchers to select the eye-gaze measurement system that best fits their research questions and target population, as well as help consumers of autism research to interpret the findings from studies that utilize eye-gaze methods with children with ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The current study found that automatic eye-tracking and manual gaze coding produced different rates of data loss and different overall patterns of results in young children with ASD. These findings show that the choice of eye-gaze system may impact the findings of a study-important information for both researchers and consumers of autism research.

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