Hypersomnia in Major Depressive Disorder: a high-density EEG investigation

描述（由申请人提供）：本提案将支持研究，并进一步培训申请人作为精神病学和睡眠障碍医学联系的临床科学家。Plante博士的目标是研究睡眠和觉醒期间抑郁症患者嗜睡的神经生理学，确定过度嗜睡的生物标志物，并最终将这些发现转化为针对情绪障碍患者的神经调节干预措施。为了实现这些目标，一个教学计划侧重于发展：1）先进的高密度脑电图（hdEEG）在情绪和睡眠障碍研究中的应用的更强的概念基础，以及2）更复杂的方法技能，包括生物统计学和临床试验设计，将补充Plante博士的临床精神病学和睡眠医学背景。培训目标将通过在医学和公共卫生的威斯康星州学校的大学提供全面的学术资源的背景下，有针对性的课程和多学科的辅导。该研究计划将利用学到的知识和新技术来调查关于睡眠过度的抑郁患者睡眠和觉醒期间皮质振荡性质的新假设，从而改变临床神经病学。将使用hdEEG在睡眠和清醒期间评价患有单相重度抑郁症（MDD）和共病嗜睡症的成人，并将其睡眠期间慢波活动和清醒期间θ/α活动的性质与健康对照组和无共病嗜睡症的MDD参与者进行对比。此外，嗜睡的MDD受试者将接受一种新型神经调节疗法--整夜慢波诱导，以检查慢波在过度嗜睡中的作用，并评估这种躯体治疗在这些患者中的疗效。这种对情绪障碍中嗜睡的生理基础的前瞻性检查旨在为申请人开发并最终测试嗜睡情绪障碍患者的新型诊断和治疗模式奠定基础，这些模式具有有意义地改善生活质量和疾病相关结局的潜力。在教学培训和这些实验产生的数据的基础上，Plante博士将把该奖项的后期阶段集中在获得临床试验设计方面的培训和开发一项随机对照试验， 使用慢波诱导作为一种新的治疗情绪障碍与共病嗜睡。在奖励期结束时，Plante博士将作为睡眠和精神疾病的完全独立研究者，在几个具有明确翻译相关性的新方向上扩展他的研究。

DESCRIPTION (provided by applicant): This proposal will support the research and further the applicant's training as a clinician-scientist at the nexus of psychiatry and sleep disorders medicine. Dr. Plante's goals are to examine the neurophysiology of hypersomnolence in depression during sleep and wakefulness, to identify biomarkers for excessive sleepiness, and to ultimately translate these findings into targeted neuromodulatory interventions for individuals with mood disorders. To achieve these aims, a didactic plan focused on the development of: 1) a stronger conceptual grounding of advanced high-density electroencephalogram (hdEEG) applications in mood and sleep disorders research, and 2) more sophisticated methodological skills including biostatistics and clinical trials design, will complement Dr. Plante's background n clinical psychiatry and sleep medicine. Training objectives will be accomplished through targeted coursework and multidisciplinary mentorship in the context of the comprehensive scholarly resources available at the University of Wisconsin School of Medicine and Public Health. The research plan will utilize knowledge and new techniques learned to investigate novel hypotheses regarding the nature of cortical oscillations during sleep and wakefulness in depressed patients with hypersomnia, and thereby alter clinical symptomatology. Adults with unipolar major depressive disorder (MDD) and co-morbid hypersomnolence will be evaluated during sleep and wake using hdEEG, and the nature of their slow wave activity during sleep and theta/alpha activity during wake contrasted with healthy controls and MDD participants without co-morbid hypersomnia. Additionally, hypersomnolent MDD participants will undergo overnight slow wave induction, a novel neuromodulatory therapy, to both examine the role of slow waves in excessive sleepiness and evaluate the efficacy of this somatic treatment in these patients. This prospective examination of the physiologic basis of hypersomnolence in mood disorders is designed to set the stage for the applicant to develop, and ultimately test, novel diagnostic and treatment modalities among hypersomnolent mood disordered patients with the potential to meaningfully improve quality of life and illness-related outcomes. Building on didactic training and data generated by these experiments, Dr. Plante will focus the latter stages of the award on obtaining training in the design of clinical trials and developing a randomized controlled trial of the use of slow wave induction as a novel treatment for mood disorders with co-morbid hypersomnia. At the end of the award period, Dr. Plante will be well-poised to extend his research in several novel directions with clear translational relevance as a fully independent investigator in sleep and psychiatric disorders.