Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances

Sleep disturbance is prevalent in youth with Autism Spectrum Disorder (ASD). Researchers have posited that circadian dysfunction may contribute to sleep problems or exacerbate ASD symptomatology. However, there is limited genetic evidence of this. It is also unclear how insomnia risk genes identified through GWAS in general populations are related to ASD and common sleep problems like insomnia traits in ASD. We investigated the contribution of copy number variants (CNVs) encompassing circadian pathway genes and insomnia risk genes to ASD risk as well as sleep disturbances in children with ASD. We studied 5860 ASD probands and 2092 unaffected siblings from the Simons Simplex Collection (SSC) and MSSNG database, as well as 7509 individuals from two unselected populations (IMAGEN and Generation Scotland). Sleep duration and insomnia symptoms were parent reported for SSC probands. We identified 335 and 616 rare CNVs encompassing circadian and insomnia risk genes respectively. Deletions and duplications with circadian genes were overrepresented in ASD probands compared to siblings and unselected controls. For insomnia-risk genes, deletions (not duplications) were associated with ASD in both cohorts. Results remained significant after adjusting for cognitive ability. CNVs containing circadian pathway and insomnia risk genes showed a stronger association with ASD, compared to CNVs containing other genes. Circadian genes did not influence sleep duration or insomnia traits in ASD. Insomnia risk genes intolerant to haploinsufficiency increased risk for insomnia when duplicated. CNVs encompassing circadian and insomnia risk genes increase ASD liability with little to no observable impacts on sleep disturbances

Investigating longitudinal associations between parent reported sleep in early childhood and teacher reported executive functioning in school-aged children with autism

Up to 80% of children with autism spectrum disorder (ASD) experience sleep disturbance. Poor sleep impairs executive functioning (EF), a lifelong difficulty in ASD. Evidence suggests EF difficulties in ASD are exacerbated by poor sleep. We examine whether early childhood sleep disturbances are associated with worsening EF trajectories in school-aged children with ASD. A subsample (n = 217) from the Pathways in ASD longitudinal study was analyzed. The Children’s Sleep Habits Questionnaire captured sleep duration, onset, and night awakenings before age 5 (mean = 3.5 years). Metacognition (MI) and Behavioral Regulation (BRI) indices, on the Teacher Behavior Rating Inventory of Executive Functioning, were used to measure cognitive and affective components of EF respectively at four time-points (7.8–11.8 years). We applied latent growth curve models to examine associations between sleep and EF, accounting for relevant covariates, including school-age sleep (mean = 6.7 years). Sleep traits had different age-related impacts on behavioral regulation, but not metacognition. Longer sleep onset at 3.5 years was associated with a worsening BRI difficulties slope (b = 2.07, p < 0.04), but conversely associated with lower BRI difficulties at 7.7 years (b = −4.14, p = 0.04). A longer sleep onset at 6.7 years was related to higher BRI difficulties at 7.7 years (b = 7.78, p < 0.01). Longer sleep duration at 6.7 years was associated with higher BRI difficulties at age 7.7 (b = 3.15, p = 0.01), but subscale analyses revealed shorter sleep duration at age 6.7 was linked to a worsening inhibition slope (b = −0.60, p = 0.01). Sleep onset is a robust early correlate of behavior regulation in children with ASD, whereas sleep duration is a later childhood correlate

Pilot study: The association between sleep and Theory of Mind in school aged children

Theory of Mind (ToM) is defined as the ability to infer a range of internal mental states of others, including beliefs, intentions, desires, and emotions. ToM is a positive predictor of children's ability to socialize effectively with peers. ToM impairments are associated with peer rejection and various psychiatric disorders. Executive functioning (EF) and emotional information processing are essential for effective use of ToM. Previous studies have found poor sleep negatively impacts both. However, the relationship between sleep, EF, and emotional information processing and ToM has not been studied. The objective of this pilot study was to examine whether ToM is associated with sleep in school aged children. It was hypothesized that shorter sleep duration and lower sleep efficiency would impair emotional information processing abilities, and in turn be associated with poorer ToM. It was further hypothesized that sleep would moderate the association between EF and ToM, so that children with shorter sleep duration and lower sleep efficiency would have poorer EF and poorer ToM and children with longer sleep duration and higher sleep efficiency would have better EF and better ToM. 31 children aged 8 – 11 years participated in the study. Their sleep duration and efficiency were monitored for 5 nights at home using actigraphy. Next, participants completed two ToM tasks: 1) The Reading the Eyes in the Mind Task, measuring affective ToM, which requires emotional information processing of facial stimuli and; 2) The Faux Pas Recognition Task, measuring affective and cognitive ToM by testing participants understanding of appropriate social situations through inferring the feelings and intentions other's. Children's EF was measured using the Continuous Performance Task and the Conners Parent Short Form. Multiple regression analyses revealed that there were no significant associations between sleep duration or efficiency and ToM performance on either task. Furthermore, sleep did not moderate the relationship between EF and ToM. This pilot study revealed no association between sleep and ToM performance in school aged children. Future studies should continue to examine this relationship with a larger, more diverse sample size, while using a variety of different tasks that tap into ToM ability.Keywords: Theory of Mind, sleep, executive functions, emotion information processing, youthLa théorie de l'esprit (TdE) est définie comme la capacité de déduire une gamme d'états mentaux internes dont des croyances, des intentions, des désirs, et des émotions. La TdE a été prouvé comme un prédicteur positif sur la capacité des enfants de socialiser efficacement avec leurs pairs. La déficience de la TdE est associée avec du rejet de la part des pairs et des troubles psychiatriques divers. Le fonctionnement exécutif (FE) et la gestion des émotions sont essentiels pour l'utilisation efficace de la TdE. Les études précédentes ont trouvé qu'un sommeil perturbé a un impact négatif sur les deux. Cependant, la relation entre le sommeil, FE, la gestion des émotions, et le développement de la TdE n'a jamais été examinée. L'objectif de ce projet pilote était d'examiner si la TdE est associée avec le sommeil des enfants de l'âge scolaire. Il était supposé que un sommeil ayant une durée plus courte et de faible efficacité serait associé avec une TdE inachevée. Il était attendu davantage que le sommeil modérait l'association entre le FE et la TdE pour que des enfants ayant un sommeil de mauvaise qualité aurait eu un FE et une TdE faibles et ceux avec un meilleur sommeil aurait eu un meilleur FE et TdE. 31 enfants l'âge de 8 à 11 ans ont participé dans l'étude. La durée et l'efficacité de leur sommeil a été surveillé pendant 5 nuits à domicile avec l'actimétrie. Ensuite, les participants ont complété deux testes de la TdE : 1) Le teste « Reading the Eyes in the Mind », mésure la TdE affective, qui besoin la gestion des émotions des stimuli faciaux, et 2) le teste « Faux Pas Recognition », mésure la TdE affective et cognitive, par testant la compréhension des participants sur les situations sociales appropriées en déduisant les sentiments et les intentions des autres. Le FE des enfants était mesuré par le teste « Continuous Performance » et le « Conners Parent Short Form ». Plusieurs analyses de régression ont démontré qu'il n'avait pas d'associations significatives entre la durée du sommeil ni l'efficacité et la performance de TdE sur chacun des testes. De plus, le sommeil n'a pas régularisé la relation entre le FE et la TdE. Ce projet pilot a démontré aucune association entre le sommeil et la performance de la TdE parmi les enfants de l'âge scolaire. D'autres études supplémentaires devrait continuer d'examiner cette relation avec une échantillon plus divers et nombreux, tandis que l'utilisation des testes différentes varies qui identifie la capacité de la TdE.Mots clés: Théorie d'esprit, sommeil, fonctionnement exécutif, gestion d'informations émotives, jeune

The Association between Sleep and Theory of Mind in School Aged Children with ADHD

Theory of Mind (ToM) is defined as the ability to infer a range of internal mental states of others, including beliefs, intentions, desires, and emotions. These abilities are associated with children’s ability to socialize effectively with peers. ToM impairments are associated with peer rejection and psychiatric disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD). Previous studies have found poor sleep negatively impacts executive functioning (EF) and emotional information processing, which are essential for the effective use of ToM. Youth with ADHD have EF deficits and sleep problems. However, the relationship between sleep, executive functioning, and ToM in children with ADHD has not been studied. In this review, we propose that the poor social and interpersonal skills characterizing individuals with ADHD could be explained by the impact of poor sleep on the emotional and cognitive mechanisms underlying ToM

The Interplay Between Sleep and Executive Functioning in Children with Autism

Study Objectives: Up to 80% of children with autism spectrum disorder (ASD) experience sleep disturbance. Poor sleep impairs executive functioning (EF), a lifelong difficulty in ASD. Evidence suggests EF impairments in ASD is exacerbated by poor sleep. We examine whether early childhood sleep disturbances are associated with worsening EF trajectories in school-aged children with ASD. Methods: A subsample (n = 217) from the Pathways in ASD longitudinal study was analyzed. The Children’s Sleep Habits Questionnaire captured sleep duration, onset, and night awakenings before age 5 (Mean = 3.5 years). Metacognition (MI) and Behavioral Regulation (BRI) indices on the Teacher Behavior Rating Inventory of Executive Functioning measured EF difficulties at four time-points (7-11 years). We applied latent growth curve models to examine associations between sleep and EF, accounting for relevant covariates, including school-age sleep (Mean = 6.7 years). Results: Longer sleep onset at 3.5 years predicted a worsening BRI difficulties slope (b = 2.07, p &lt; 0.04), but conversely predicted lower BRI difficulties at age 7.7 (b = -4.14, p = 0.04). A longer sleep onset at age 6.7 predicted higher BRI difficulties at age 7.7 (b = 7.78, p &lt; 0.01). Longer sleep duration at age 6.7 predicted higher BRI difficulties at age 7.7 (b = 3.15, p = 0.01), but subscale analyses revealed shorter sleep duration at age 6.7 predicted a worsening inhibition slope (b = -0.597, p = 0.01). Conclusions: Different sleep phenotypes have different age-related impacts on selective behavioral regulation components, but not metacognition. Delayed sleep onset is a robust early predictor, whereas shorter sleep duration is a later predictor of worsening behavior regulation in school-aged children with ASD