CHRONOBIOGICAL BASES OF PREMENSTRUAL SLEEP AND MOOD DISORDERS

我们之前报告了一例患有经前综合征的患者，其中睡眠/觉醒和核心体温节律表现为卵泡期的相位提前和黄体期的相位延迟。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，发现雌激素促进视交叉上核内PER2基因的昼夜节律表达，而对Pen基因的表达无影响，提示视交叉上核内PER1和PER2基因受雌激素的不同调控。这些结果为经前综合征卵泡期进展提供了一个解释。对雌激素分子机制的进一步分析表明，雌激素引起的PER2基因表达的时相提前主要受视交叉上核内SRC-1和Clock的相互作用的调节。我们对8名健康女性应用了超短时睡眠-醒来时间表，并研究了在卵泡期和黄体期睡眠倾向、嗜睡、直肠温度以及血清褪黑素、促甲状腺激素和皮质醇浓度的每日波动。黄体期核心体温、褪黑素总分泌量、促甲状腺激素和皮质醇节律的幅度显著降低，嗜睡和白天慢波睡眠的发生率显著增加。月经周期中白天慢波睡眠的差异与每日平均直肠温度的差异呈正相关。这些发现表明，黄体期昼夜节律振荡的幅度可能受到抑制。黄体期白天嗜睡的增加可能与白天慢波睡眠的增加有关，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.