CHRONOBIOGICAL BASES OF PREMENSTRUAL SLEEP AND MOOD DISORDERS

我们先前曾报告一位罹患经前症候群的病人，其睡眠/觉醒与核心体温节律在卵泡期呈现相位提前，而在黄体期呈现相位延迟。为了观察卵巢类固醇激素对昼夜节律起搏器的影响，我们进行了动物实验，发现雌激素使视交叉上核Per 2基因的昼夜节律表达时相提前，但对Pen基因的昼夜节律表达没有影响，表明视交叉上核Per 1和Per 2基因受雌激素的差异调节。这些结果为经前期综合征卵泡期的相位提前提供了解释。进一步分析雌激素作用的分子机制发现，雌激素诱导Per 2基因表达的时相提前主要受视交叉上核SRC-1和CLOCK相互作用的调控。我们对8名健康女性采用了超短睡眠-觉醒时间表，并研究了卵泡期和黄体期睡眠倾向、嗜睡、直肠温度和血清褪黑激素、促甲状腺激素和皮质醇浓度的昼夜波动。在黄体期，核心体温的幅度，总褪黑激素分泌，TSH和皮质醇节律的幅度显着下降，而嗜睡和发生在白天的慢波睡眠显着增加。月经周期中白天慢波睡眠量的差异与每日平均直肠温度的差异呈正相关。研究结果表明，在黄体期，昼夜节律振荡的幅度可能会受到抑制。黄体期白天嗜睡增加可能与白天慢波睡眠增加有关，这可能是由于黄体期体温调节的变化。

We previously reported a patient suffering from premenstrual syndrome in which sleep/wake and core body temperature rhythms displayed phase advances in the follicular phase and phase delays in the luteal phase. To see effects of ovarian steroid hormones on the circadian pacemaker, we conducted animal experiments and found that estrogen phase-advanced the circadian expression of Per2 gene in the suprachiasmatic nucleus but had no effects on that of Pen gene, suggesting that Per1 and Per2 genes in the suprachiasmatic nucleus were differentially regulated by estrogen. These results provide an explanation for phase advances in the follicular phase in premenstrual syndrome. Further analyses on molecular mechanisms of estrogen revealed that the phase advance of Per2 gene expression caused by estrogen was mainly regulated by interactions between SRC-1 and CLOCK in the suprachiasmatic nucleus. We applied an ultrashort sleep-wake schedule to eight healthy women and studied diurnal fluctuations in sleep propensity, sleepiness, rectal temperature, and serum concentrations of melatonin, thyroid-stimulating hormone, and cortisol in the follicular and luteal phases. In the luteal phase, amplitude of core body temperature, total melatonin secretions, and amplitudes of TSH and cortisol rhythms were significantly decreased, whereas sleepiness and occurrence of slow-wave sleep during the daytime were significantly increased. Differences in the amount of daytime slow-wave sleep across the menstrual cycle were positively correlated with differences in the daily mean rectal temperature. The findings suggest that the amplitude of circadian oscillation may be dampened in the luteal phase. Increased daytime sleepiness in the luteal phase may be associated with increased daytime slow-wave sleep, due possibly to changes in thermoregulation in the luteal phase.