SLEEP-GUIDED PET STUDIES IN DEPRESSION

抑郁症中的睡眠引导宠物研究

• 批准号: 6694085
• 负责人: ERIC A. NOFZINGER
• 金额: $ 33.53万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-12 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694085
• 关键词: REM sleep; auditory stimulus; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain metabolism; clinical research; deoxyglucose; electroencephalography; emotions; generation difference; glucose metabolism; human middle age (35-64); human subject; hypothalamus; major depression; neuroanatomy; neurobiology; neurophysiology; performance; positron emission tomography; prefrontal lobe /cortex; sleep; wakefulness; young adult human (21-34)

DESCRIPTION: (Adapted from applicant's abstract) This revised resubmission of an ROl proposal (MH 61566) 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. The investigators developed this model from several sources of information. These included EEG sleep studies in depression, preclinical studies defining brain mechanisms of behavioral state regulation, human sleep functional brain imaging studies, functional brain imaging studies in depressed subjects and evidence from our preliminary studies using the proposed experimental paradigm. The investigators propose 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. The investigators further 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). The investigators hypothesize that depressed patients suffer from functional deficits in the anterior paralimbic and prefrontal cortex systems. This leads to maladaptive behavior. In a compensatory fashion, the generalized arousal system increases its function, albeit unsuccessfully since the effector structures in the anterior paralimbic and prefrontal cortex are dysfunctional. The slow wave sleep disturbances in depression are related to 1) the cortical deficits in prefrontal cortex and anterior paralimbic structures, and 2) inhibition of slow wave sleep due to the increased function in the generalized arousal system. This inhibits the spontaneous occurrence of low frequency thalamocortical electrical oscillations characteristic of slow wave sleep. The sleep continuity and REM sleep disturbances are related to the increased function in the generalized arousal system, structures known to be important in the maintenance of wakefulness and in the generation of REM sleep. To test features of this model, 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. Behavioral correlates of behavioral state changes in depression will include formal assessments of mood, vigilance and performance. Repeated measures multivariate analyses of covariance and multivariate multiple regressions will test the above hypotheses. Findings from this study are expected to significantly advance our understanding of the pathophysiology of depression.

描述：（改编自申请人的摘要）此修订的重新提交 ROL建议（MH 61566）将测试功能性神经解剖模型 抑郁症的行为状态（睡眠/唤醒）的变化被认为是 抑郁病理生理学的中心。调查人员开发了这个 来自多个信息来源的模型。其中包括脑电图研究 抑郁，临床前研究，定义了行为状态的大脑机制 调节，人睡眠功能性脑成像研究，功能性大脑 对沮丧的受试者的成像研究和我们的初步研究的证据 使用所提出的实验范式。调查人员建议 抑郁症患者遭受两个相关行为状态的变化：缺陷 在慢波睡眠的产生和维护中，措施增加 与行为唤醒有关，包括睡眠连续性和REM睡眠 干扰。调查人员进一步建议这些变化是相关的 在两个相关大脑系统中的功能改变：1） 旁皮和额叶皮层系统（前扣带回，基部前脑， 下丘脑和前额叶皮层）； 2）广义唤醒系统 （丘脑网状形成，丘脑和杏仁核）。调查人员 假设抑郁症患者患有功能性缺陷 前旁皮和前额叶皮层系统。这导致适应不良 行为。以补偿方式，广义的唤醒系统增加 它的功能，尽管没有成功，但由于效应子结构 前旁皮和前额叶皮层功能失调。慢波 抑郁症的睡眠障碍与1）皮质缺陷有关 前额叶皮层和前旁皮结构和2）抑制慢 由于广义唤醒系统功能增加而导致的波浪睡眠。 这抑制了低频丘脑皮质的自发发生 慢波睡眠的电振荡特征。睡眠连续性 REM睡眠障碍与功能的增加有关 广义唤醒系统，已知在维护中很重要的结构 清醒和雷姆睡眠的产生。测试此功能 模型，我们将招募27种抑郁门诊患者和27个健康对照 五天的睡眠大脑成像研究。行为状态的度量包括脑电图 睡眠和区域定量脑电图。大脑功能的度量包括-FDG 宠物相对区域葡萄糖代谢在醒来，NREM和REM睡眠期间。 抑郁症行为状态变化的行为相关性将包括 对情绪，警惕和表现的正式评估。重复措施 协方差和多元回归的多元分析将 测试上述假设。这项研究的发现预计 显着提高了我们对抑郁症病理生理学的理解。