EBioMedicineAug 21, 2016

Changes in Internal Body Clock Timing in Mania and Mixed Mood Episodes Return to Normal After Bipolar Disorder Treatment

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

Circadian phases during acute manic episodes in bipolar disorder (BD) patients were found to be ~7 hours advanced.

Circadian rhythms of BD patients differed in phase during acute mood episodes compared to recovered states.
In 23 acute manic episodes, the circadian phases were approximately 7 hours advanced, equivalent to about 17 hours delayed.
Treatment led to the normalization of circadian phases in 21 out of 23 manic cases, with two cases normalizing by a 17-hour advance.
In three mixed manic episodes, circadian phases were delayed by approximately 6-7 hours.
Five depressive episodes exhibited circadian phases that were delayed by about 4-5 hours.
Post-treatment, the circadian phases of BD patients resembled those of healthy controls.

Simplified

Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.

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Changes in Internal Body Clock Timing in Mania and Mixed Mood Episodes Return to Normal After Bipolar Disorder Treatment

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