CHRONOBIOLOGICAL EVALUATION OF RAPID-CYCLING BIPOLAR DISORDER

快速循环双相情感障碍的时间生物学评估

• 批准号: 2578775
• 负责人: E LEIBENLUFT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2578775
• 关键词: bioperiodicity; bipolar depression; clinical research; cortisol; electroencephalography; human subject; longitudinal human study; melatonin; prolactin; sleep disorders; somatotropin; thyrotropin

Patients with rapid-cycling bipolar disorder (RCBD) experience at least four episodes of affective illness (depression, hypomania, and/or mania) in a year. Their mood cycles are associated with changes in the sleep- wake cycle, and sleep deprivation experiments demonstrate that these sleep-wake changes are not merely symptoms of the illness, but have pathogenic significance. These observations raise the question of whether circadian dysregulation and/or dysregulation in the sleep-wake cycle are involved in the pathogenesis of RCBD, and whether stabilization of these physiological systems could have beneficial clinical effects. In this project we are performing a series of cross-sectional and longitudinal studies designed to address the first of these questions. In the cross-sectional study, patients are admitted to the hospital for brief, intensive evaluations of circadian rhythms and sleep once shortly after they switch into hypomania, and once shortly after they switch into depression. The hospitalizations are each 48 hours in duration and consist of a 20-hour "naturalistic day," during which patients sleep and eat ad lib, and a 28-hour constant routine designed to minimize the effects of light, sleep, activity, and caloric loading on the patient's circadian rhythms. During the hospitalizations, patients wear rectal temperature probes, sleep is monitored by EEG, and blood is withdrawn every thirty minutes through an indwelling intravenous catheter. Blood samples are used to measure melatonin, TSH, cortisol, prolactin and growth hormone. Data from the first twelve patients indicate that there is a trend for the onset of melatonin secretion to be shifted earlier in hypomania, compared with depression. The other hormonal data are currently being analyzed. Analysis of the EEG data does not show any differences between the two mood states. Data from a small number of patients studied longitudinally are consistent with these cross-sectional data in generally showing a delay is maximal (i.e. early vs. late in the episode). In addition to these studies, we have used data from controls participating in other studies in the Branch to obtain preliminary information as to whether, and how, patients' and controls' sleep and melatonin rhythms may differ. This analysis shows that patients with RCBD have relatively delayed time of nocturnal melatonin onset and of sleep onset. In addition, patients with RCBD appear to have decreased duration of melatonin secretion. Based on these data, we propose a model whereby the symptoms of the illness (fluctuating levels of activation and fluctuating sleep duration) cause unstable entrainment, which in turn exacerbates the instability in the sleep-wake cycle and the symptoms of the illness. According to this model, stabilizing circadian rhythms could have beneficial clinical effects, a hypothesis that we test in ZO1 MH 02688-03 CPB.

快速循环型双相情感障碍(RCBD)患者至少经历过 四种情感性疾病(抑郁、轻躁狂和/或躁狂) 一年后。他们的情绪周期与睡眠的变化有关- 唤醒周期和睡眠剥夺实验证明这些 睡眠-觉醒的变化不仅是疾病的症状，而且 致病意义。这些观察结果提出了这样一个问题： 睡眠-觉醒周期中的昼夜节律失调和/或失调 在RCBD的发病机制中起重要作用，以及这些细胞是否稳定 生理系统可能会产生有益的临床效果。在这 我们正在进行一系列横截面和纵向的 旨在解决第一个问题的研究。 在横断面研究中，患者被送往医院接受治疗 短时间内对昼夜节律和睡眠进行简短、密集的评估 在他们变成轻躁狂之后，有一次他们很快就变成了 抑郁症。每次住院时间为48小时， 由20个小时的“自然主义的一天”组成，在这一天中，患者睡眠和 和一个28小时不变的程序，旨在最大限度地减少 光照、睡眠、活动和卡路里负荷对患者的影响 昼夜节律。在住院期间，患者穿着直肠 体温探头，睡眠由脑电监测，血液被抽走 每隔30分钟通过静脉留置导管。血样 样本用于测定褪黑素、促甲状腺激素、皮质醇、催乳素和 生长激素。来自前12名患者的数据表明， 褪黑素分泌的开始是一种趋势 与抑郁症相比，轻躁狂症。其他荷尔蒙数据是 目前正在分析中。对脑电数据的分析没有显示出任何 两种情绪状态之间的差异。数据来自少数几个 纵向研究的患者与这些横截面一致 通常显示延迟的数据是最大的(即 一集)。 除了这些研究，我们还使用了来自对照的数据 参加分部的其他学习以获得初步的 关于患者和对照组的睡眠和睡眠是否以及如何 褪黑激素的节律可能有所不同。这一分析表明，RCBD患者 夜间褪黑激素起效时间和睡眠时间相对延迟 开始了。此外，RCBD患者的病程似乎缩短了。 褪黑激素的分泌量。 基于这些数据，我们提出了一个模型，在这个模型中， 疾病(活动水平波动和睡眠时间波动) 导致不稳定的夹带，这反过来又加剧了 睡眠-觉醒周期和疾病症状。根据这一点 模型，稳定昼夜节律可能对临床有益 效应，这是我们在ZO1 MH 02688-03 CPB中检验的一个假设。