Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

Adherence to treatment and parents' perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances.

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents' perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

Sleep disturbances are associated with irritability in ASD children with sensory sensitivities.

BACKGROUND: Parent reports suggest that 44-84% of children with ASD exhibit sleep disturbances that are of clinical concern. Previous studies have reported that, in children with ASD, the severity of sleep disturbances is associated with the severity of either sensory problems or aberrant behaviors, but none have performed combined analyses with measures of both sensory and aberrant behaviors symptom domains from the same children. METHODS: We examined parent reports of 237 children with ASD, 1.4-8.7 years old, using the child sleep habits questionnaire (CSHQ), sensory profile (SP), and aberrant behaviors checklist (ABC). RESULTS: The analyses revealed that sleep disturbances were most strongly associated with SP sensory sensitivity and ABC irritability scores. Together these scores explained 35% of the variance in total CSHQ scores. Moreover, sensory sensitivity scores moderated the association between irritability and sleep disturbances, indicating that sleep disturbances were significantly associated with irritability only in children with moderate to severe sensory sensitivities. CONCLUSION: We suggest that the three symptom domains may interact and exacerbate each other such that successful intervention in one symptom domain may have positive impact on the others. Further intervention studies testing this hypothesis are highly warranted.

Children with autism exhibit similar longitudinal changes in core symptoms when placed in special or mainstream education settings.

LAY ABSTRACT: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.

The Importance of Language Delays as an Early Indicator of Subsequent ASD Diagnosis in Public Healthcare Settings.

Previous studies have reported that ASD children with more severe symptoms are diagnosed earlier. However, previous studies in community settings have mostly relied on retrospective parental reports without the use of quantitative standardized test scores. Here, we evaluated the association of language, cognitive, and ASD severity standardized scores with the age of diagnosis in 1-6-year-old children diagnosed in a public healthcare setting. The results revealed that language scores were the strongest variable associated with the age of diagnosis, explaining ~ 30% of the variability across children. Indeed, all children diagnosed before 30-months of age exhibited moderate-to-severe language delays. These results further substantiate the prominence of language delay as a highly visible symptom associated with earlier ASD diagnosis in community clinical settings.

Early diagnosis of autism in the community is associated with marked improvement in social symptoms within 1-2 years.

LAY ABSTRACT: It is widely believed that early diagnosis and treatment of autism spectrum disorder is essential for better outcome. This is demonstrated by the American Academy of Pediatrics recommendation to screen all 1.5-2.5-year-old toddlers for autism spectrum disorder. However, multiple longitudinal studies of children diagnosed with autism spectrum disorder at 1.5-6 years of age and treated in community settings have not reported any associations between earlier diagnosis and improved outcome in core autism spectrum disorder symptoms. In this study, we measured changes in core autism spectrum disorder symptoms over a 1-2-year period in 131 children diagnosed with autism spectrum disorder at 1.2-5 years of age, and treated in the community. The results revealed that children who were diagnosed before 2.5 years of age were three times more likely to exhibit considerable improvements in social autism spectrum disorder symptoms in comparison to children diagnosed at later ages. These results highlight the importance of early diagnosis and treatment of autism spectrum disorder even in community settings with heterogeneous services. In addition, these results motivate further prioritization of universal screening for autism spectrum disorder before 2.5 years of age.

Sleep Disturbances and Sensory Sensitivities Co-Vary in a Longitudinal Manner in Pre-School Children with Autism Spectrum Disorders.

Previous research has demonstrated that sleep disturbances are positively correlated with sensory sensitivities in children with ASD. Most of these studies, however, were based on cross-sectional analyses, where the relationship across symptom domains was examined at a single time-point. Here, we examined the development of 103 pre-school children with ASD over a 1-3-year period. The results revealed that spontaneous longitudinal changes in sleep disturbances were specifically correlated with changes in sensory sensitivities and not with changes in other sensory processing domains nor with changes in core ASD symptoms. These finding demonstrate a consistent longitudinal relationship between sleep disturbances and sensory sensitivities, which suggests that these symptoms may be generated by common or interacting underlying physiological mechanisms.

Young Autism Spectrum Disorder Children in Special and Mainstream Education Settings Have Similar Behavioral Characteristics.

In many countries, parents can place autism spectrum disorder (ASD) children in either mainstream or special education settings, which differ in their ability to provide structured early intervention programs. There are no clear guidelines for how to make initial placement decisions and ongoing debate about the benefits and drawbacks of each educational setting. Previous studies have mostly examined placement of school-age children and reported that those with poorer cognitive abilities and more severe ASD symptoms tend to be placed in special education. The placement of younger children has rarely been studied. Here, we utilized the database at the National Autism Research Center of Israel to examine whether ASD severity, cognitive abilities, and parent education influenced the placement of 242 children. We performed the analyses separately for 1-3-year-old children who were placed in daycare centers and 3-5-year-old children who were placed in pre-school kindergartens. Our analyses revealed surprisingly small differences across special and mainstream education settings, particularly in daycare centers. Cognitive scores and parent education were significantly higher in ASD children placed in mainstream education, but these differences were of moderate effect size and explained a relatively small percentage of the variability in placement choices (<15%). Indeed, we found considerable overlap in the characteristics of ASD children across educational settings, which suggests that initial placement decisions are performed with little regard to the children's abilities. Given the importance of optimal early intervention, further studies are warranted to determine whether children with specific abilities and needs benefit more from placement in either educational setting. LAY SUMMARY: Currently, there are no clear recommendations for placing young children with ASD in special versus mainstream education settings. We examined the influence of ASD severity, cognitive abilities, and parent education on the initial placement of 242 children. While we found significantly higher cognitive scores and parental education in children placed in mainstream education, there was a remarkable overlap in the characteristics of children across both settings, suggesting that initial placement is performed with limited regard to the children's abilities. Autism Res 2021, 14: 699-708. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Language regression is associated with faster early motor development in children with autism spectrum disorder.

Language regression (LR) is a consistent and reproducible phenomenon that is reported by ~25% of parents who have children with autism spectrum disorder (ASD). However, there is controversy regarding the etiological and clinical significance of this phenomenon. Here, we examined data from a cohort of 218 children with ASD from the Negev Autism Center in Israel. We identified 36 children with ASD who were reported to exhibit clear LR by their parent on three independent occasions and compared them to 104 children whose parents did not report any concern of regression (NR). We compared a variety of key developmental characteristics across these two groups. We found that the age at which children with ASD in the LR group achieve key developmental milestones of crawling, walking, and use of first words is significantly younger than the age of children in the NR group, and comparable to the age of typically developing children. In contrast, no differences were observed in physical growth characteristics such as head circumference, weight, or height between the groups. Furthermore, almost all children with LR were born close to full term (>35 weeks) and none had a history of hypotonia. Notably, despite their apparently typical early development, children with LR were diagnosed with more severe symptoms of ASD than children with NR. These results strengthen the motivation to continue and study LR among children with ASD and suggest that early detection and intervention studies of ASD may benefit from stratifying children into LR and NR groups. Autism Res 2020, 13: 145-156. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The presence of language regression (LR) among children with autism is still a matter of scientific debate. Here, we show that children with autism and reported LR start to crawl, talk, and walk at the same age as other typically developing children and significantly earlier than other children with autism. These findings, along with other medical differences between these groups, suggest that children who experienced LR comprise a distinct subgroup within the autism spectrum.

Quantifying the social symptoms of autism using motion capture.

Autism Spectrum Disorder (ASD) is a remarkably heterogeneous condition where individuals exhibit a variety of symptoms at different levels of severity. Quantifying the severity of specific symptoms is difficult, because it either requires long assessments or observations of the ASD individual, or reliance on care-giver questionnaires, which can be subjective. Here we present a new technique for objectively quantifying the severity of several core social ASD symptoms using a motion capture system installed in a clinical exam room. We present several measures of child-clinician interaction, which include the distance between them, the proportion of time that the child approached or avoided the clinician, and the direction that the child faced in relation to the clinician. Together, these measures explained ~30% of the variance in ADOS scores, when using only ~5 minute segments of "free play" from the recorded ADOS assessments. These results demonstrate the utility of motion capture for aiding researchers and clinicians in the assessment of ASD social symptoms. Further development of this technology and appropriate motion capture measures for use in kindergartens and at home is likely to yield valuable information that will aid in quantifying the initial severity of core ASD symptoms and their change over time.

Sleep disturbances are associated with specific sensory sensitivities in children with autism.

Background: Sensory abnormalities and sleep disturbances are highly prevalent in children with autism, but the potential relationship between these two domains has rarely been explored. Understanding such relationships is important for identifying children with autism who exhibit more homogeneous symptoms. Methods: Here, we examined this relationship using the Caregiver Sensory Profile and the Children's Sleep Habits Questionnaire, which were completed by parents of 69 children with autism and 62 age-matched controls. Results: In line with previous studies, children with autism exhibited more severe sensory abnormalities and sleep disturbances than age-matched controls. The sleep disturbance scores were moderately associated with touch and oral sensitivities in the autism group and with touch and vestibular sensitivities in the control group. Hypersensitivity towards touch, in particular, exhibited the strongest relationship with sleep disturbances in the autism group and single-handedly explained 24% of the variance in total sleep disturbance scores. In contrast, sensitivity in other sensory domains such as vision and audition was not associated with sleep quality in either group. Conclusions: While it is often assumed that sensitivities in all sensory domains are similarly associated with sleep problems, our results suggest that hypersensitivity towards touch exhibits the strongest relationship with sleep disturbances when examining children autism. We speculate that hypersensitivity towards touch interferes with sleep onset and maintenance in a considerable number of children with autism who exhibit severe sleep disturbances. This may indicate the existence of a specific sleep disturbance mechanism that is associated with sensitivity to touch, which may be important to consider in future scientific and clinical studies.

Brief Report: The Negev Hospital-University-Based (HUB) Autism Database.

Elucidating the heterogeneous etiologies of autism will require investment in comprehensive longitudinal data acquisition from large community based cohorts. With this in mind, we have established a hospital-university-based (HUB) database of autism which incorporates prospective and retrospective data from a large and ethnically diverse population. The collected data includes social-demographic characteristics, standardized behavioral testing, detailed clinical history from electronic patient records, genetic samples, and various neurological measures. We describe the initial cohort characteristics following the first 18 months of data collection (188 children with autism). We believe that the Negev HUB autism database offers a unique and valuable resource for studying the heterogeneity of autism etiologies across different ethnic populations.