Project 1: The impact of sleep dysregulations on Autism Spectrum Disorder

睡眠失调对自闭症谱系障碍的影响：摘要 多达80%的自闭症谱系障碍（ASD）儿童经历睡眠中断。这些 是ASD患儿父母报告的最严重的症状之一。不足 主观睡眠质量与核心ASD症状的严重程度相关，包括 重复行为，社交和沟通困难。然而，客观睡眠的PSG很少 研究没有发现显著的影响。这可能反映了少数研究利用了 PSG作为一种客观的睡眠测量，小样本量，或在实验室环境中评估，而不是 而不是在孩子的家庭环境中。我们自己的一个更大的样本使用睡眠PSG的调查， ASD受试者，在他们的家中，发现ASD的SWS比率增加，REM睡眠比率降低 与发育正常（TD）的儿童和青少年相比。为了解决关键问题， 睡眠失调是否是ASD发展和症状的核心，我们将测试 睡眠碎片（体动记录）、睡眠结构（PSG）和白天、清醒、休息时的差异 在150名ASD患者和75名年龄和性别匹配的TD对照中，年龄4-17岁。我们将 检查任何观察到的睡眠失调是否与核心症状，重复性 行为和ASD的认知功能。我们还将研究睡眠障碍是否与 与TD相比，ASD患者的日间静息状态EEG失调。与项目2合作， 我们将研究目标实现诱导的睡眠正常化是否会对这些产生积极影响。 症状与项目3和项目4合作，我们将检查假设的损伤是否在 ASD患者的睡眠片段化、睡眠结构和白天清醒、静息状态EEG将 在我们的ASD遗传模型的睡眠动物实验中，如果睡眠正常化， 在我们的ASD动物模型中， 与改善社会沟通和认知有关，并减少重复行为， 这些动物模型。如果我们证明睡眠片段化是导致 一些ASD的特征和睡眠正常化使他们变得更好，我们将证明他们的潜力。 睡眠在ASD中的重要性和因果关系

The impact of sleep dysregulation on Autism Spectrum Disorder: Abstract As many as 80% of children with Autism Spectrum Disorder (ASD) experience sleep disruptions. These are among the most burdensome symptoms reported by parents of children with ASD. Insufficient subjective sleep quality is associated with exacerbated severity of core ASD symptoms, including repetitive behaviors, social and communication difficulties. However, the few objective sleep PSG studies have not found significant effects. This likely reflects the small number of studies that utilized PSG as an objective sleep measure, small sample sizes, or assessment in a laboratory setting rather than in the child's home environment. Our own investigation of a larger sample using sleep PSG in ASD subjects, in their home, found an increased SWS ratio in ASD and a lower REM sleep ratio compared to typically developing (TD) children and adolescents. To address the critical question of whether dysregulated sleep is central to the development and symptoms of ASD, we will test for differences in sleep fragmentation (actigraphy), sleep architecture (PSG) and daytime, awake, resting state EEG, in 150 individuals with ASD and 75 age and sex-matched TD controls, age 4-17. We will examine if any observed sleep dysregulation is associated with the core symptoms, repetitive behaviors, and cognitive function of ASD. We will also examine if sleep impairments are associated with dysregulated daytime, resting state EEG in ASD compared to TD. In collaboration with Project 2, we will examine if target engagement-induced normalization of sleep positively impacts these symptoms. In collaboration with Projects 3 and 4, we will examine if the hypothesized impairments in sleep fragmentation, sleep architecture and daytime awake, resting state EEG in ASD will be recapitulated in our animal experiments of sleep in genetic models of ASD and if normalization of sleep fragmentation, sleep architecture and daytime awake, resting EEG in our animal models of ASD will be associated with improved social communication and cognition, and reduced repetitive behaviors in these animal models. If we demonstrate that sleep fragmentation is responsible for the development of some ASD traits and sleep normalization alleviates them, we will have demonstrated the potential causality and importance of sleep in ASD.