The Circadian System of Patients with Bipolar Disorder Differs in Episodes of Mania and Depression

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.