Resilience is a dynamic process through which people adjust to adversity and buffer anxiety and depression. The COVID-19 global pandemic has introduced a shared source of adversity for people across the world, with detrimental implications for mental health. Despite the pronounced vulnerability of autistic adults to anxiety and depression during the COVID-19 pandemic, relationships among autism-related traits, resilience, and mental health outcomes have not been examined. As such, we aimed to describe the relationships between these traits in a sample enriched in autism spectrum traits during the COVID-19 pandemic. We also aimed to investigate the impact of demographic and social factors on these relationships. Across three independent samples of adults, we assessed resilience factors, autism-related traits, anxiety symptoms, and depression symptoms during the COVID-19 pandemic. One sample (recruited via the Autism Spectrum Program of Excellence, n = 201) was enriched for autism traits while the other two (recruited via Amazon Mechanical Turk, n = 624 and Facebook, n = 929) drew from the general population. We found resilience factors and quantitative autism-related traits to be inversely related, regardless of the resilience measure used. Additionally, we found that resilience factors moderate the relationship between autism-related traits and depression symptoms such that resilience appears to be protective. Across the neurodiversity spectrum, resilience factors may be targets to improve mental health outcomes. This approach may be especially important during the ongoing COVID-19 pandemic and in its aftermath.

Autism spectrum disorder (ASD) comprises a multi‐dimensional set of quantitative behavioral traits expressed along a continuum in autistic and neurotypical individuals. ASD diagnosis—a dichotomous trait—is known to be highly heritable and has been used as the phenotype for most ASD genetic studies. But less is known about the heritability of autism spectrum quantitative traits, especially in adults, an important prerequisite for gene discovery. We sought to measure the heritability of many autism‐relevant quantitative traits in adults high in autism spectrum traits and their extended family members. Among adults high in autism spectrum traits (n = 158) and their extended family members (n = 245), we calculated univariate and bivariate heritability estimates for 19 autism spectrum traits across several behavioral domains. We found nearly all tested autism spectrum quantitative traits to be significantly heritable (h2 = 0.24–0.79), including overall ASD traits, restricted repetitive behaviors, broader autism phenotype traits, social anxiety, and executive functioning. The degree of shared heritability varied based on method and specificity of the assessment measure. We found high shared heritability for the self‐report measures and for most of the informant‐report measures, with little shared heritability among performance‐based cognition tasks. These findings suggest that many autism spectrum quantitative traits would be good, feasible candidates for future genetics studies, allowing for an increase in the power of autism gene discovery. Our findings suggest that the degree of shared heritability between traits depends on the assessment method (self‐report vs. informant‐report vs. performance‐based tasks), as well as trait‐specificity. Lay Summary We found that the scores from questionnaires and tasks measuring different types of behaviors and abilities related to autism spectrum disorder (ASD) were heritable (strongly influenced by gene variants passed down through a family) among autistic adults and their family members. These findings mean that these scores can be used in future studies interested in identifying specific genes and gene variants that are associated with different behaviors and abilities related with ASD.

Autistic children and adults often have sleep disturbances, which may affect their and their family's quality of life. Yet, the relationship between sleep-wake patterns and autism spectrum traits is understudied. Identifying such relationships could lead to future research elucidating common mechanistic underpinnings. Thus, we aimed to determine whether sleep-wake patterns, specifically related to sleep, physical activity, and the daily sleep-wake rhythm (i.e., circadian rhythm), are associated with autism spectrum-related traits. Accelerometer-derived sleepwake parameters were estimated in individuals with autistic spectrum traits and their family members (N = 267). We evaluated autism spectrum traits using the Social Responsiveness Scale (SRS) to assess the presence and severity of social impairment and the Behavior Rating Inventory of Executive Function (BRIEF) to assess executive function. The linear multivariate regression analysis (using SOLAR-Eclipse) showed that in adults, increased core autism spectrum traits and executive dysfunction were associated with disruption of several sleep-wake parameters, particularly related to the daily sleep-wake rhythm, and that executive dysfunction was associated with disrupted sleep quality and level of physical activity. We highlight the interplay between daytime function and disrupted sleep-wake patterns, specifically related to the daily sleep-wake rhythm, that could guide future research into common mechanisms. Lay SummaryAutistic children and adults often report sleep disturbances. To dissect the relationship between a range of autism spectrum traits and sleep-wake patterns, we assessed social interaction and executive function in participants who also wore actimetry watches on their wrists to assess their sleep-wake patterns. We found that increased impairments in social and executive function occurred with Stacey D. Elkhatib Smidt and Arpita Ghorai should be considered joint first authors.

There is uncertainty among researchers and clinicians about how to best measure autism spectrum dimensional traits in adults. In a sample of adults with high levels of autism spectrum traits and without intellectual disability (probands, n = 103) and their family members (n = 96), we sought to compare self vs. informant reports of autism spectrum-related traits and possible effects of sex on discrepancies. Using correlational analysis, we found poor agreement between self- and informant-report measures for probands, yet moderate agreement for family members. We found reporting discrepancy was greatest for female probands, often self-reporting more autism-related behaviors. Our findings suggest that autism spectrum traits are often underrecognized by informants, making self-report data important to collect in clinical and research settings. Supplementary Information The online version contains supplementary material available at 10.1007/s10803-022-05822-6.

Introduction Children and adults with autism spectrum disorder (ASD) often have sleep, circadian, and executive function impairments, which can affect daytime quality. Yet, the relationship between sleep or circadian traits and ASD traits is still unknown. Thus, we aimed to determine if sleep and circadian traits were associated with ASD traits, including executive function. Methods We studied data from participants with and without ASD enrolled in the family-based study Autism Spectrum Program of Excellence (ASPE), University of Pennsylvania. We used GGIR to analyze actigraphy-derived sleep and circadian traits from 250 participants (219 adults ages 18–87 years, mean 44.2 ± 17.3 years; 31 children ages 4–17 years, mean 11.3 ± 3.9 years). These traits were compared to ASD traits (social impairment and restricted/repetitive behavior via Social Responsiveness Scale, Second Edition) and executive function (Behavior Rating Inventory of Executive Function) using linear multivariate regression models adjusted for age, age2, and sex via Sequential Oligogenic Linkage Analysis Routines. Results In adults, earlier start time of the 10 hours of highest activity in a 24-hour day (M10 start time; p = 0.02), decreased robustness of the rest/activity rhythm (relative amplitude; p = 0.03), and increased intradaily variability of rest/activity rhythm (p = 0.04) were associated with more social impairment. In children, earlier M10 start time (p = 0.02) and decreased relative amplitude (p = 0.03) were associated with more social impairment. In adults, higher average 5-hour period of lowest activity in a 24-hour day (L5 average; p = 0.03), lower average 10-hour period of highest activity in a 24-hour day (M10 average; p = 0.005), earlier M10 start time (p = 0.02), decreased relative amplitude (p = <0.001), increased intradaily variability (p = <0.001) and decreased sleep efficiency (p = 0.04) were associated with increased executive function impairment. In children, earlier M10 start time (p = 0.006) and intradailty variability (p = 0.008) were associated with increased executive function impairment. Conclusion Circadian traits are significantly associated with ASD traits, including executive function, suggesting the importance of sleep-wake rhythm dysfunction in ASD. Support (if any) Anonymous donor; NIH T32HL07713; University of Pennsylvania’s Institute for Translational Medicine and Therapeutics

OBJECTIVES/GOALS: Autism spectrum disorder (ASD) is characterized by difficulties in communication and social interaction as well as restricted and repetitive behaviors. Sleep problems are a common concern in children with ASD that can persist into adulthood. This study aims to further explore sleep in ASD without intellectual disability (ASD w/o ID). METHODS/STUDY POPULATION: We recruited individuals of both sexes with ASD w/o ID (probands) and relatives as part of the Autism Spectrum Program of Excellence (ASPE) at the University of Pennsylvania. Actimetry data were collected via a wrist-worn tri-axial accelerometer for 21 days. Data from 212 participants were considered. We analyzed sleep data using the algorithms GGIR, ChronoSapiens, and PennZzz. The sleep traits of proband and sibling pairs were compared using paired t-test or Wilcoxon signed-rank test. We used the Social Responsiveness Scale, Second Edition (SRS-2) to assess social impairment and restricted/repetitive traits. We compared SRS-2 scores to sleep traits using partial Spearman or Pearson correlations adjusting for age (171 participants). RESULTS/ANTICIPATED RESULTS: Probands demonstrated later sleep onset (p = 0.03), decreased M10 average (10-hour period of highest activity/day; p = 0.006), decreased relative amplitude (measure of rest-activity rhythm; p <0.001), and decreased total daytime activity (p = 0.005) compared to siblings. Regarding social function and restricted/repetitive traits, adult males showed an inverse correlation between SRS-2 total score and sleep efficiency (r = −0.2, p = 0.04) and a positive correlation between SRS-2 total score and intradaily variability (r = 0.3, p = 0.02). Adult females showed an inverse correlation between SRS-2 total score and M10 average (r = −0.3, p = 0.02) and between SRS-2 total score and relative amplitude (self-report r = −0.4, p = 0.001; informant r = −0.3, p = 0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: This study focuses on the analysis of sleep traits in ASD including the relationship between social function and sleep. Thus far, the most robust findings are decreased daytime activity and relative amplitude in individuals with ASD w/o ID compared to siblings. We have also shown that ASD social impairment may be related to sleep dysfunction.

Introduction Sleep problems are a common concern in children with autism spectrum disorder (ASD) that can persist into adulthood. This study aims to further explore sleep in ASD without intellectual disability (ASD w/o ID). Methods We recruited individuals with ASD w/o ID (probands) and relatives as part of the Autism Spectrum Program of Excellence (ASPE) at the University of Pennsylvania. Actimetry data were collected via a wrist-worn tri-axial accelerometer for 21 days. Data from 212 participants were considered. We analyzed sleep data using the algorithms GGIR, ChronoSapiens, and PennZzz. The sleep traits of proband and sibling pairs were compared using paired t-test or Wilcoxon signed-rank test. We used the Social Responsiveness Scale, Second Edition (SRS-2) to assess social impairment and restricted/repetitive traits. We compared SRS-2 scores to sleep traits using partial Spearman or Pearson correlations adjusting for age (171 participants). Results Probands demonstrated later sleep onset (p = 0.03), decreased M10 average (10-hour period of highest activity/day; p = 0.006), decreased relative amplitude (measure of rest-activity rhythm; p&lt;0.001), and decreased total daytime activity (p = 0.005) compared to siblings. Regarding social function and restricted/repetitive traits, adult males showed an inverse correlation between SRS-2 total score and sleep efficiency (r = -0.2, p= 0.04) and a positive correlation between SRS-2 total score and intradaily variability (r = 0.3, p = 0.02). Adult females showed an inverse correlation between SRS-2 total score and M10 average (r = -0.3, p = 0.02) and between SRS-2 total score and relative amplitude (self-report r = -0.4, p = 0.001; informant r = -0.3, p = 0.005). Conclusion This study focuses on the analysis of sleep traits in ASD including the relationship between social function and sleep. Thus far, the most robust findings are decreased daytime activity and relative amplitude in individuals with ASD w/o ID compared to siblings. We have also shown that ASD social impairment may be related to sleep dysfunction. Support NIH T32HL07713, anonymous donor, and the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania.