Sleep Imaging Studies in Depression

描述(申请人提供)：脑电睡眠的可靠变化是抑郁症的特征，尽管这些变化的神经生物学仍不清楚。我们实验室的初步发现表明，抑郁症患者存在两种相关的行为状态变化：慢波睡眠的生成和维持存在缺陷，与行为唤醒相关的指标增加，包括睡眠连续性和快速眼动睡眠障碍。我们认为这些变化与两个相关脑系统的功能改变有关：1)前缘和前额叶皮质系统(前扣带回、基底前脑、下丘脑和前额叶皮质)；2)全身性觉醒系统(桥脑网状结构、丘脑和杏仁核)。 促进这一研究的职业发展活动集中在三个方面：1)神经生物学研究在纵向临床试验中的应用；2)边缘/前额叶皮质相互作用的认知神经科学及其在抑郁症睡眠功能神经解剖学中的应用；3)抑郁症边缘/前额叶皮质相互作用的药物调节。K24奖的研究计划将测试抑郁症行为状态(睡眠/清醒)变化的功能性神经解剖学模型，这些变化被认为是抑郁症病理生理学的核心。我们将招募27名抑郁症门诊患者和27名健康对照参加为期五天的睡眠脑成像研究。行为状态的测量包括脑电、睡眠和局部定量脑电。脑功能的测量包括-FDG PET清醒时、NREM和REM睡眠时的相对局部糖代谢。重复测量、多变量协方差分析和多变量多元回归将检验上述假设。该计划之前已被资助为R01“抑郁症中的睡眠引导PET研究”(EA Nofzinger，P1，MH61566)。这项研究的发现有望极大地促进我们对抑郁症的病理生理学的理解。 指导活动的目标是每年至少从医学生、住院医生或博士后研究员队伍中招募和指导一名新的实习生。指导的成功将通过学员在同行评议的出版物中的生产率、在科学会议上的研究报告以及对独立职业发展奖和资金提案的追求来衡量。首席研究员将指导学员进行以患者为中心的研究，包括开发IRB批准的方案，实施研究计划，以及解释和提交数据。指导年轻研究人员的内容领域包括睡眠中使用的功能神经成像方法，行为状态调节的神经科学，以及研究的伦理行为。

DESCRIPTION (provided by applicant): Reliable changes in EEG sleep characterize depression although the neurobiology of these changes remain unknown. Preliminary findings from our lab suggest that depressed patients suffer from two related behavioral state changes: deficits in the generation and maintenance of slow wave sleep, and increases in measures related to behavioral arousal including sleep continuity and REM sleep disturbances. We propose that these changes are related to functional alterations in two related brain systems: 1) an anterior paralimbic and prefrontal cortex system (anterior cingulate, basal forebrain, hypothalamus and prefrontal cortex); and 2) a generalized arousal system (pontine reticular formation, thalamus and amygdala). Career development activities to further this line of investigation focus on three areas: 1) the application o neurobiological studies to longitudinal clinical trials; 2) the cognitive neuroscience of limbic/prefrontal cortex interactions and their applications to the functional neuroanatomy of sleep in depression; and 3) the pharmacologic modulation of limbic/prefrontal cortex interactions across behavioral states in depression. The research plan of the K24 award will test a functional neuroanatomic model of behavioral state (sleep/wake) changes in depression that are proposed to be central to the pathophysiology of depression. We will recruit 27 depressed outpatients and 27 healthy controls into a five-day sleep brain imaging study. Measures of behavioral state include EEG sleep and regional quantitative EEG. Measures of brain function include -FDG PET relative regional glucose metabolism during waking, NREM and REM sleep. Repeated measures multivariate analyses of covariance and multivariate multiple regressions will test the above hypotheses. This plan has previously been funded as the R01 "Sleep-guided PET studies in depression" (EA Nofzinger, P1, MH61 566). Findings from this study are expected to significantly advance our understanding of the pathophysiology of depression. The goals of mentoring activities are to recruit and mentor at least one new trainee per year from the ranks of medical students, residents, or post-doctoral fellows. Success in mentoring will be measured by trainee's productivity in peer-reviewed publications, presentations of research at scientific meetings, and pursuit of independent career development awards and funding proposals. The principal investigator will mentor trainees in conducting patient* oriented research, including the development of IRB approved protocols, implementing a research plan, and interpreting and presenting data. Content areas for mentoring young investigators include functional neuroimaging methods for use during sleep, the neuroscience of behavioral state regulation, and in the ethical conduct of research.