Investigating the Role of Slow-wave Activity as a Marker of Impaired Plasticity in Major Depressive Disorder

项目摘要 主要 二 抑郁症（MDD）是最普遍的精神疾病，据估计是最常见的精神疾病。 全球残疾的主要原因。然而，MDD的标准治疗通常需要至少2-3个月， 数周才见效，延长了疾病负担。为了创造新的、快速起效的疗法， 了解负责MDD开发和维护的基本机制， needed.它 氯胺酮 MDD。 假设目前快速抗抑郁干预措施中的共同因素，包括 睡眠剥夺是突触可塑性的一种变化，这种变化被认为是在睡眠中受损的。 睡眠期间的慢波活动（SWA）与调节突触可塑性有关;然而， SWA、可塑性和抑郁症之间的联系尚未确定。拟议的研究旨在 通过测试在睡眠期间扰乱SWA可以 防止可塑性的稳态下降，从而增加可塑性，改善个体的情绪 关于MDD在这个指导以病人为导向的研究职业发展奖（K23）的应用程序， 候选人将在基于其专业知识的跨学科培训背景下追求这些研究目标 睡眠稳态在抑郁症和睡眠研究方法中的作用（1） 神经科学 刺激， 包括 临床 培训 突触可塑性和多模式评估方法（例如，经颅磁 清醒EEG分析，BDNF测量），（2）定量EEG高级培训 分析方法，以及（3）MDD研究的高级培训（例如，MDD的神经生物学，以及 这些培训目标将支持候选人的长期目标，即成为一名 独立的翻译科学家在以病人为导向的研究，是中央执行 提出研究计划。四十 历史 男性和女性MDD（25-50岁），以及一组20名对照， 在实验室里度过两个晚上：一个是基线睡眠，另一个是基线睡眠。 其中慢波睡眠将利用经验证的过程被中断。以下 标记 间接 血清 将 波 每个实验室夜晚， 与净突触强度和可塑性相关的神经元将使用几个独立的，但 指标包括从经颅磁刺激导出的清醒EEG θ功率度量， 衍生的BDNF，以及学习和记忆的行为测量。据预测，MDD患者 表现出与基线时缺乏净突触强度和可塑性相关的标志物， 中断将使这些措施正常化，从而改善情绪 , .该项目有可能 确定睡眠影响MDD情绪的机制，这可以为新的开发提供信息。 干预措施。

PROJECT SUMMARY Major second Depressive Disorder (MDD) is the most prevalent mental illness, and has been estimated to be the leading cause of disability worldwide. However, standard treatments for MDD typically take at least 2-3 weeks to take effect, prolonging disease burden. In order to create novel, fast-acting therapies, a better understanding of the underlying mechanisms responsible for the development and maintenance of MDD is needed. It ketamine MDD. is hypothesized that the common factor among current rapid antidepressant interventions, including and sleep deprivation, is a change i n synaptic plasticity, which has been suggested to be impaired in Slow-wave activity (SWA) during sleep has been implicated in modulating synaptic plasticity; however the link between SWA, plasticity, and depression has yet to be determined. The proposed research aims to examine the role of sleep SWA in modulating mood by testing the model that disrupting SWA during sleep can prevent homeostatic decreases in plasticity, thereby increasing plasticity and improving mood in individuals with MDD. In this Mentored Patient-Oriented Research Career Development Award (K23) application, the candidate will pursue these research aims in the context of interdisciplinary training that builds on her expertise in the role of sleep homeostasis in depression and sleep research methodology with (1) neuroscience stimulation, including clinical training in the of synaptic plasticity and multi-modal assessment methods (e.g., transcranial magnetic analysis of waking EEG, measurement of BDNF), (2) advanced training in quantitative EEG analytic approaches, and (3) advanced training in MDD research (e.g., neurobiology of MDD, and trials methodology).These training goals will support the candidate's long term goal of becoming an independent translational scientist in patient-oriented research, and are central to the execution of the proposed research plan. Forty history males and females with MDD (25-50 yo), and a group of twenty controls with no of mood disorders will spend two nights in the laboratory: one baseline night of sleep, and one night where slow-wave sleep will be disrupted utilizing a validated procedure. Following markers indirect serum will wave each laboratory night, associated with net synaptic strength and plasticity will be assessed using several independent, but indices including waking EEG theta power metrics derived from t ranscranial magnetic stimulation, derived BDNF, and behavioral measures of learning and memory. It is predicted that those with MDD exhibit markers associated with deficient net synaptic strength and plasticity at baseline, and that slow- disruption will normalize these measures, thereby improving mood , . This project has the potential to identify the mechanisms by which sleep affects mood in MDD, which could inform the development of novel interventions.