Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Bipolar Disord. 2015 May;17(3):303-14. doi: 10.1111/bdi.12270. Epub 2014 Oct 31.
Bipolar disorder is a common psychiatric disease characterized by mood disturbances with alternating episodes of mania and depression. Moreover, disturbances in the sleep/wake cycle are prevalent. We tested a hypothesis that the function of the circadian system, which drives the sleep/wake cycle, may differ in patients with bipolar disorder depending on whether they are experiencing an episode of mania or depression.
To assess the functional state of the central circadian clock, daily profiles of melatonin levels in saliva were determined. The functional state of the peripheral clocks was assessed by determining daily profiles of Per1 and Nr1d1 clock gene expression in buccal mucosa cells. Sixteen patients with bipolar disorder in a manic episode, 22 patients in a depressive episode, and 19 healthy control subjects provided samples at regular intervals during a 24-hour cycle.
During episodes of mania, the daily profiles of melatonin differed compared with healthy controls and patients in an episode of depression, mainly due to elevated melatonin levels during the daytime. No difference was found between melatonin profiles of control subjects and patients in depression. The Per1 and Nr1d1 profiles were advanced in patients in mania compared with those in depression. Compared with controls, a trend toward an advance was apparent in the profiles of patients during an episode of mania but not depression. The amplitude of the Nr1d1 expression profile was higher in mania than in depression.
The data revealed differences in the functional state of the circadian system in patients with bipolar disorder depending on whether they were experiencing a manic or a depressive episode.
双相情感障碍是一种常见的精神疾病，其特征为心境障碍，伴有躁狂和抑郁发作的交替。此外，睡眠/觉醒周期紊乱也很常见。我们提出了一个假设，即昼夜节律系统的功能，它驱动睡眠/觉醒周期，可能在双相情感障碍患者中有所不同，具体取决于他们是否经历躁狂或抑郁发作。
为了评估中枢生物钟的功能状态，我们通过测定唾液中褪黑素水平的日常变化来评估。外周时钟的功能状态通过测定颊粘膜细胞中 Per1 和 Nr1d1 时钟基因表达的日常变化来评估。16 名处于躁狂发作的双相情感障碍患者、22 名处于抑郁发作的患者和 19 名健康对照者在 24 小时周期内定期提供样本。
在躁狂发作期间，褪黑素的日常变化与健康对照组和抑郁发作患者不同，主要是由于白天褪黑素水平升高。对照组和抑郁组患者的褪黑素曲线没有差异。与抑郁患者相比，躁狂患者的 Per1 和 Nr1d1 曲线提前。与对照组相比，躁狂发作患者的曲线在躁狂发作期间出现了提前的趋势，但在抑郁发作期间没有。Nr1d1 表达曲线的振幅在躁狂症中高于抑郁症。
这些数据表明，双相情感障碍患者的昼夜节律系统功能状态存在差异，具体取决于他们是否经历躁狂或抑郁发作。
