Robust Circadian Rhythms Associated with Fewer Relapses in Bipolar Disorder

Post by Elisa Guma

The takeaway

Individuals with bipolar disorder often experience relapses (depressive or manic episodes) despite engaging in maintenance therapy. Robust circadian rhythm activity may be associated with fewer of these relapses, particularly for depressive episodes. 

What's the science?

Circadian rhythm disruption is often observed in individuals with bipolar disorder and may be linked to mood. These disruptions may be linked to depressive or manic episode relapses, which about 1/3 of patients experience within 1 year of initial onset, despite maintenance therapy. Objectively measured circadian rhythm activity has not been measured in individuals with bipolar disorder. This week in Translational Psychiatry, Esaki and colleagues prospectively studied the relationship between circadian rhythm activity and mood episodes in individuals with bipolar disorder.

How did they do it?

Outpatients with bipolar disorder (n=218; 19 excluded) underwent a baseline clinical and behavioural assessment in which depressive and manic behaviours were recorded. For the following 7 consecutive days participants wore an accelerometer on the wrist of their non-dominant hand for 24h/day (apart from bathing), which recorded their activity levels. Additionally, they were asked to record their bedtimes and rising times in a sleep diary. Following the baseline assessment, participants were followed up to 12 months for mood episode relapses.

To analyze the activity data acquired from the accelerometer, the authors identified the amplitude and onset of the least active continuous 5-hour period, as well as the amplitude and onset of the most active continuous 10-hour period. They then investigated differences in these measures between individuals who experienced mood episode relapses, either depressive or manic. 

What did they find?

Of the participants, 46% experienced mood episodes during the 12-month follow-up period, of which 39% were depressive episodes, and 19% were manic, hypomanic, or mixed. The authors observed a significant association between mood and circadian rhythm activity. More specifically, higher activity levels, particularly during the 10 most active hours, were associated with a decrease in mood episode relapse, particularly for depressive episodes. Thus, higher physical activity during waking hours may be associated with better outcomes for individuals with bipolar disorder. In contrast, if the onset of this 10-hour active period occurred later in the day, there was an increased likelihood of mood episodes, both for depressive and manic/hypomanic episodes. However, the association between late onset of the active period and manic episodes was not significant following covariation for several factors including age, gender, residual mood symptoms, mood episodes within the year prior to the baseline assessment, total sleep time, sleep efficiency, and daylight availability. This suggests that the increased likelihood of relapse may be associated with higher activity levels that are not aligned with normative sleep-wake cycles.

What's the impact?

This study found that robust circadian rhythm activity, characterized by higher physical activity during waking, may be associated with a decrease in mood relapses, particularly for depressive episodes, in individuals with bipolar disorder. Later timing of circadian activity rhythm was associated with an increase in relapse for depressive episodes. Further research is needed to understand the influence of medication on these associations, as well as the directionality of these relationships, i.e., do disruptions in circadian rhythm activity result in mood relapse, or can these changes be used as potential biomarkers to identify when a relapse may occur?

Esaki et al. Association between circadian activity rhythms and mood episode relapse in bipolar disorder: a 12-month prospective cohort study. Translational Psychiatry (2021). Access the original scientific publication here.