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: 5203775
• 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/5203775
• 关键词: bipolar depression; bipolar depression depressed phase; bipolar depression manic phase; blood chemistry; body physical activity; body temperature; circadian rhythms; cortisol; electroencephalography; hormone regulation /control mechanism; human subject; longitudinal human study; melatonin; patient monitoring device; prolactin; psychobiology; saliva; sleep; somatotropin; thermometry; thyrotropin

Patients with rapid-cycling bipolar disorder (RCBD) experience at least four episodes of affective illness (depression, hypomania, and/or mania) in a year and are frequently resistant to conventional treatments. Whereas the gender ratio among patients with bipolar illness is 1:1, bipolar women are three times more likely than bipolar men to develop a rapid-cycling course. Therefore, this illness warrants study because of its significant morbidity and because it can yield information about the effects of gender on the course of bipolar disorder. In addition, since rapid-cycling patients experience frequent mood shifts that are accompanied by dramatic changes in the sleep-wake cycle, they are an interesting population in which to study the relationships between sleep, circadian rhythms, and mood disorders. This project consists of three studies of the chronobiology of RCBD: (1) a cross-sectional study of patients in the depressed and hypomanic states; (2) an intensive longitudinal study of a small number of patients; and (3) the collection of naturalistic longitudinal data (mood ratings and sleep logs) on all patients in our RCBD clinic. In the cross-sectional study, patients are admitted to the hospital for brief, intensive chronobiological evaluations 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. The constant routine is 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patients wear rectal temperature probes and activity monitors, sleep is monitored by EEG, and blood is withdrawn every thirty minutes through an indwelling intravenous catheter.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 ten patients indicate that there is a trend such that the onset of melatonin secretion and the maximum of the smoothed cortisol rhythm are phase-advanced (shifted earlier) in the hypomanic, compared to the depressed, phase. We are currently expanding the sample in this study to see if these findings reach statistical significance. In addition to this cross-sectional study, we are conducting intensive longitudinal studies of the circadian rhythms of melatonin, temperature, and sleep in several patients with RCBD. These studies allow us to understand in greater detail the relationship between these rhythms and the patients' mood states. Finally, we have accumulated a large naturalistic data set that has allowed us to demonstrate a circadian rhythm in the direction of mood switches in patients with RCBD, and to explore the relationship between prior sleep (sleep duration, times of sleep and wake onset) and mood.

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） 并且通常对常规治疗有抵抗力。 而双相情感障碍患者的性别比例为1：1， 双相女性比双相男性更有可能发展为 快速循环课程。 因此，这种疾病值得研究，因为 它的显著发病率，因为它可以产生有关的信息， 性别对双相情感障碍病程的影响 另外由于 快速循环患者经历频繁的情绪变化， 伴随着睡眠-觉醒周期的剧烈变化，它们是一种 有趣的人群中，研究睡眠， 昼夜节律和情绪障碍。 该项目包括三个 RCBD的时间生物学研究：（1）RCBD的横断面研究， 患者在抑郁和轻躁狂状态;（2）强化 少数患者的纵向研究;（3）收集 自然主义的纵向数据（情绪评级和睡眠日志）， 我们RCBD诊所的病人 在横断面研究中，患者入院接受治疗， 在他们完成实验后不久， 在他们进入轻度躁狂后不久， 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小时不间断的日常生活。 不变的惯例是 旨在最大限度地减少光线、睡眠、活动和热量的影响 影响病人的昼夜节律 在住院期间， 患者佩戴直肠温度探头和活动监测器， 通过EEG监测，每隔30分钟通过 留置静脉导管 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 的数据 前十名患者表明，有一种趋势， 褪黑激素分泌和最大的平滑皮质醇节律是 在《易经》中，以“先易后难”为先。 抑郁阶段 我们目前正在扩大这项研究的样本 看看这些发现是否有统计学意义。 除了这项横向研究，我们正在进行密集的 对褪黑激素，温度， 和睡眠中的几个病人RCBD。 这些研究使我们能够 更详细地了解这些节奏之间的关系， 患者的情绪状态。 最后，我们积累了大量的 一组自然的数据，让我们能够证明 RCBD患者情绪转换方向的节律，以及 探索先前睡眠（睡眠时间， 睡眠和觉醒发作）和情绪。