Shifted Circadian Phase in Manic Episode was Returned to Normal after Treatment in Bipolar Disorder

Abstract

Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). However, mechanisms for circadian dysregulation of BD have not been clearly identified. We observed circadian rhythms from acute exacerbation to recovery states in hospitalized patients with BD, and compared them with rhythms of healthy control participants. Included in the study were 31 mood episodes of 26 BD patients, and 18 healthy control measurements. Clinical symptoms were evaluated at baseline, repeated 2 weeks intervals during hospitalization and right before discharge. All participants wore wrist actigraphs during the studies. Sample collections of saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days for healthy controls. From BP patients, sample collections were performed with the same schedule in baselines and repeated at 2 weeks intervals during hospitalization and just before discharge. Molecular circadian rhythms had different phases during acute BD compared to phases in the recovered states. For manic episodes, there were three types classified according to their phases. In acute states, type 1 phases were about 7 hours advanced, type 2 were about 17 hours delayed, and type 3 were about 6∼7 hours delayed. For depressive episodes, circadian rhythms phases were about 4∼5 hours delayed in acute states. After treatment, circadian phases resembled those of healthy controls. Circadian rhythm phase shifts might be a causal mechanism of BD, and we suggest that there are three types of circadian rhythm phase shift in mania.