Sleep-dependent negative overgeneralization in peri-pubertal anxiety

项目总结 睡眠越来越被认为是大脑健康和发育的关键因素。 90%以上患有焦虑症的年轻人存在睡眠问题，预计会恶化 症状，并且在与治疗相关的焦虑缓解后不能解决，留下这些 处于持续危险中的青年(审查见McMakin等人，2015年)。然而，我们几乎没有可测试的模型。 关于与睡眠有关的问题如何以及为什么会影响年轻人的心理健康，这使得 很难理解风险病理学并精确干预。睡眠和焦虑都是 异构性和在不同开发中的显著差异，使情况进一步复杂化。 从睡眠对于认知和情感功能的已知角色得出的模型(例如， 记忆巩固、情绪调节)来解释这些过程中的干扰如何 需要在发展的敏感期出现特定的症状才能推动油田的发展 往前走。为此，我们正在进行的R01旨在测试我们的理论模型，即 睡眠神经生理学的关键特征(例如，宏观觉醒、纺锤活动)影响情绪 反应性和记忆加工，以驱动消极的过度概化(目标1和2)。我们也 检查这种睡眠依赖的过程是否可以修改(目标3)。尽管在方法论上 复杂性和全球流行病，我们即将完成AIMS 1和AIMS的数据收集工作 2(96%；n=192/200)，结果支持我们模型的关键特征。副刊是 要求支持关键完成目标3(n=60)，我们在该目标中注意 修改这些流程的可能性。具体地说，我们将使用定向内存重新激活 在睡眠期间操作哪些记忆被选择用于巩固。如果我们能成功 修改内存选择，这会导致睡眠微结构的变化 减少消极的过度泛化，我们不仅将在我们的 不仅如此，我们也将为干预工作做好准备。

PROJECT SUMMARY Sleep is increasingly understood as a critical contributor to brain health and development. Problems with sleep are present in more than 90% of youth with anxiety, predict worsening symptoms, and do not resolve following treatment-related remission of anxiety, leaving these youth at ongoing risk (for review see McMakin et al., 2015). Yet, we have few testable models for exactly how and why sleep-related problems impact mental health in young people, making it hard to understand risk pathology and intervene with precision. Both sleep and anxiety are heterogeneous and vary significantly across development, further complicating the picture. Models that draw from the known roles of sleep for cognitive and affective functions (e.g., memory consolidation, emotion regulation) to explain how disruptions in these processes could drive specific symptoms during sensitive periods of development are needed to move the field forward. To this end, our ongoing R01 aims to test our theoretical model whereby disruptions in key features of sleep neurophysiology (e.g., macro-arousals, spindle activity) impact emotional reactivity and memory processing to drive negative overgeneralization (Aims 1 and 2). We also examine whether this sleep-dependent process is modifiable (Aim 3). Despite methodological complexity and a global pandemic, we are nearing completion of data collection for Aims 1 and 2 (96%; n=192/200) with results supporting key features of our model. The supplement is requested to support the critical completion of Aim 3 (n=60) in which we turn our attention to the potential to modify these processes. Specifically, we will use targeted memory reactivation during sleep to manipulate which memories are selected for consolidation. If we can successfully modify memory selection and this leads to changes in sleep microstructure coincident with a reduction in negative overgeneralization, we will not only gain support for causality within our model but also, we will be well-positioned for intervention work.