CHRONOBIOLOGICAL EVALUATION OF RAPID-CYCLING BIPOLAR DISORDER

快速循环双相情感障碍（RCBD）患者至少经历了 4次情感性疾病发作（抑郁、轻躁狂和/或躁狂） 在一年内。 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表明，这些 睡眠-觉醒的变化不仅仅是疾病的症状， 致病意义这些观察结果提出了一个问题， 昼夜节律失调和/或睡眠-觉醒周期中的失调 参与RCBD的发病机制，以及是否稳定这些 生理系统可能具有有益的临床效果。在这 项目我们正在执行一系列的横截面和纵向 旨在解决第一个问题的研究。 在横断面研究中，患者入院接受治疗， 对昼夜节律和睡眠进行简短、密集的评估， 在他们转换成轻躁狂之后， 萧条每次住院时间为48小时， 包括20小时的"自然日"，在此期间，患者睡觉， 随意进食，28小时的日常工作旨在最大限度地减少 光线、睡眠、活动和热量负荷对患者的影响 昼夜节律在住院期间，患者穿直肠 温度探头，睡眠由EEG监测，并抽血 每隔30分钟通过留置静脉导管注射一次。血液 样本用于测量褪黑激素，促甲状腺激素，皮质醇，催乳素和 生长激素.前12名患者的数据表明， 褪黑激素分泌的开始有提前的趋势， 轻度躁狂与抑郁症相比。其他的荷尔蒙数据是 目前正在分析中。脑电图数据分析没有显示任何 两种情绪状态之间的差异。数据来自少数 纵向研究的患者与这些横截面一致， 数据通常显示延迟是最大的（即， episode）。 除了这些研究，我们还使用了来自对照组的数据， 参与分支的其他研究， 关于患者和对照组的睡眠是否以及如何改变的信息， 褪黑激素节律可能不同。该分析表明，RCBD患者 夜间褪黑激素起效和睡眠时间相对延迟 发病此外，RCBD患者的持续时间似乎缩短， 褪黑激素的分泌。 基于这些数据，我们提出了一个模型， 疾病（活动水平波动和睡眠持续时间波动） 导致不稳定的夹带，这反过来又加剧了不稳定， 睡眠-觉醒周期和疾病的症状。根据该 模型，稳定昼夜节律可以有有益的临床 效应，我们在ZO1 MH 02688 - 03 CPB中检验的假设。

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 During the hospitalizations, patients wear rectal temperature probes, sleep is monitored by EEG, and blood is withdrawn every thirty minutes through an indwelling intravenous catheter.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.