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

项目总结 主修 第二 抑郁症(MDD)是最常见的精神疾病，据估计是 全球导致残疾的主要原因。然而，MDD的标准治疗通常至少需要2-3次 几周后生效，延长了疾病负担。为了创造新的、快速有效的疗法，更好的 对开发和维护MDD的基本机制的理解是 需要的。它 氯胺酮 MDD。 假设当前快速抗抑郁干预的共同因素包括 睡眠不足，是突触可塑性的一种变化，已被认为在 睡眠中的慢波活动(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。这项拟议的研究旨在 通过测试睡眠中干扰SWA的模型来检验睡眠SWA在调节情绪中的作用 防止体内平衡的可塑性下降，从而增加可塑性和改善个人情绪 使用MDD。在这项以患者为本的导师研究职业发展奖(K23)申请中， 应聘者将在其专业知识的基础上进行跨学科培训，以实现这些研究目标 睡眠动态平衡在抑郁症中的作用及睡眠研究方法(1) 神经科学 刺激， 包括 临床 培训中的 突触可塑性和多模式评估方法(例如，经颅磁 清醒脑电分析，脑源性神经营养因子测量)，(2)定量脑电高级训练 分析方法，以及(3)MDD研究方面的高级培训(例如MDD的神经生物学，以及 试验方法)。这些培训目标将支持候选人成为一名 独立的翻译科学家，以患者为导向的研究，是执行 提出了研究计划。四十 历史 患有MDD的男性和女性(25-50岁)，以及一组20名没有 情绪障碍患者将在实验室度过两晚：一晚是基线睡眠，另一晚是 其中慢波睡眠将使用有效的程序被扰乱。跟随 标记 间接 血清 将要 波浪 每个实验室之夜， 与净突触强度和可塑性相关的将使用几个独立的 指数包括从经颅磁刺激得出的清醒EEG theta功率度量， 衍生的脑源性神经营养因子，以及学习和记忆的行为测量。据预测，患有MDD的人 表现出与基线时净突触强度和可塑性不足相关的标记，而慢- 中断将使这些措施正常化，从而改善情绪 ， 。这个项目有可能 确定睡眠影响MDD患者情绪的机制，这可能会为新的 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.