The role of insufficient sleep and depression on hippocampal-dependent memory trajectories across the adolescent transition

项目概要 这项 K08 提案将解决我们对睡眠不足影响的基础知识中的一个关键差距 和抑郁症对纵向睡眠依赖性记忆发展的影响，并将帮助该申请人做好准备， 凯瑟琳·西蒙博士将成为一名独立的转化研究者，在睡眠、记忆、 和跨发展的精神病理学。青春期抑郁症是一个日益严重的公共卫生问题， 症状在向青春期过渡期间（9 -12 岁）1 开始，并增加患病风险 长期有害的心理和认知结果。20-21 与其他临床疾病相比， 抑郁症与海马依赖性 (HcDep) 记忆（例如陈述性记忆）的特定缺陷有关 记忆）。9-11 尽管与抑郁相关的记忆缺陷背后的大脑机制并不 据了解，一个潜在的风险因素可能是睡眠不足（例如，睡眠时间短、时间不固定或 质量差）考虑到睡眠在支持新的海马依赖性记忆形成中发挥着关键作用 （睡眠依赖性记忆 [Hc-SDM]）。12 向青春期的过渡是一个特别脆弱的时期， 涉及睡眠模式日益剧烈的变化。2,3 尽管几个晚上睡眠不足并不会 持续影响青少年的 HcDep 记忆表现18,50-53；典型的每周睡眠不足是 与海马体积减少有关。19 目前，很明显我们的 了解睡眠不足、抑郁和 Hc-SDM 的个人轨迹 青少年过渡以及这些因素之间的纵向关联。为了解决这个问题， 将使用重复测量突发设计和抽样对 27 名青春期前儿童（9 至 12 岁）进行评估 使用个性化移动健康 (mHealth) 平台，在一年内每季度进行一次。每季度 评估，连续7天，参与者将完成每日睡眠日记、生态瞬间 评估和 Hc-SDM 任务。假设睡眠不足和抑郁症状 青少年的转变将预测长期的 Hc-SDM 表现轨迹缺陷。本指导临床 科学家研究职业发展奖将支持西蒙博士的培训目标，以获取技能和 1) 使用移动医疗获得自然、纵向认知和临床评估方面的专业知识 和可穿戴设备，2）临床儿科研究培训，3）强化重复测量分析。 这些培训目标将以西蒙博士之前在认知神经科学和临床心理学方面的培训为基础 以及短期实验性睡眠依赖性记忆研究方面的专业知识。此外，培训博士。 西蒙将从这K08中获得成为独立开发转化者的重要一步 研究员，将直接导致我未来的 R01 应用，以进一步评估纵向轨迹 睡眠不足和抑郁症状对老年青少年 Hc-SDM 记忆的影响并确定关键窗口 其中基于睡眠的干预措施可以支持抑郁青少年的认知轨迹。

Project Summary This K08 proposal will address a critical gap in our fundamental knowledge of the effects of insufficient sleep and depression on longitudinal sleep-dependent memory development and will prepare this applicant, Katharine Simon, PhD, to become an independent translational investigator with expertise in sleep, memory, and psychopathology across development. Depression in adolescence is a growing public health concern, with symptoms beginning during the transition to adolescence (9 -12 years)1 and conferring heightened risk for long-term deleterious psychological and cognitive outcomes.20-21 In contrast to other clinical disorders, depression is associated with specific deficits in hippocampal-dependent (HcDep) memory (e.g., declarative memory).9-11 Although the brain mechanisms underlying depression-related memory deficits are not understood, one potential risk factor may be insufficient sleep (e.g., short sleep duration, variable timing, or poor quality) given the critical role of sleep in supporting new hippocampal-dependent memory formation (sleep dependent memory [Hc-SDM]).12 The transition to adolescence is a particularly vulnerable time that involves increasingly dramatic changes to sleep patterns.2,3 Although a few nights of insufficient sleep does not consistently affect HcDep memory performance in adolescents18,50-53; typical insufficient weekly sleep is associated with reduced hippocampal volume.19 At present, it is clear there is a fundamental gap in our knowledge of the individual trajectories of insufficient sleep, depression, and Hc-SDM across the adolescent transition and the longitudinal associations between these factors. To address this question, 27 pre-adolescents (9 to 12 years) will be assessed using a repeated measurement-burst design with sampling at quarterly intervals over a year using a personalized, mobile health (mHealth) platform. At each quarterly evaluation, for 7 consecutive days, participants will complete daily sleep diaries, ecological momentary assessments, and Hc-SDM tasks. The hypothesize is that insufficient sleep and depression symptoms across the adolescent transition will predict long-term Hc-SDM performance trajectory deficits. This Mentored Clinical Scientist Research Career Development Award will support Dr. Simon’s training goals to acquire skills and knowledge in 1) gaining expertise in naturalistic, longitudinal cognitive and clinical assessment using mHealth and wearable devices, 2) training in clinical pediatric research, and 3) intensive repeated-measure analyses. These training aims will build on Dr. Simon’s prior training in cognitive neuroscience and clinical psychology and expertise in short-term experimental sleep-dependent memory research. Furthermore, the training Dr. Simon will gain from this K08 is an essential step to become an independent developmental translational researcher and will directly lead to my future R01 application to further evaluate the longitudinal trajectories of insufficient sleep and depressive symptoms on older adolescents’ Hc-SDM memory and identify key windows in which sleep-based interventions can support cognitive trajectories in depressed adolescents.