A recent study published in eBioMedicine explored the effects of lithium on circadian rest-activity in individuals with bipolar disorder (BD). BD is characterized by extreme mood fluctuations and irregular activity patterns, with disruptions to circadian rhythms often observed. Lithium, the gold-standard treatment for BD, has been suggested to influence circadian rhythms, but the exact mechanisms, particularly in BD patients, remain unclear. This study provides new evidence on how lithium affects circadian rhythms, offering clues to its therapeutic mechanisms.
Circadian rhythms regulate the 24-hour cycle of physical, mental, and behavioral changes in the body, including sleep-wake cycles and activity levels. In BD, these rhythms are often disrupted, leading to erratic sleep patterns, manic episodes, and fluctuating mood states. BD patients commonly experience delayed circadian phase, less stable activity patterns, and heightened mood variability, which may contribute to the severity of their symptoms. Research into how treatments like lithium might influence these rhythms could shed light on improving therapeutic strategies for BD.
The study involved 35 BD patients aged 18 or older, recruited from community mental health teams and primary care at Oxford. Participants were diagnosed with BD and experienced significant mood instability. They were randomly assigned to receive either lithium treatment or a placebo for six weeks. Lithium was administered as prolonged-release lithium carbonate tablets, starting with a dose of 400 mg/day, adjusted to maintain a serum level of 0.7 mmol/L.
The patients’ circadian rest-activity was measured daily using actigraphs, which track motor activity. The study used non-parametric analysis to examine activity levels during the least active five-hour period (L5) and the most active ten-hour period (M10). It also evaluated variability in activity levels and onset times. Linear mixed models analyzed the impact of lithium on activity patterns, onset times, and their variability.
The study revealed several significant effects of lithium on circadian rhythms and activity patterns. Lithium treatment resulted in a substantial reduction in M10 levels (the most active period of the day) over the course of the study. Specifically, M10 levels dropped by 18.8% in the first week and progressively decreased to 30.9% by week 4, compared to the placebo group.
Furthermore, lithium treatment was found to increase the volatility, or flexibility, of M10 activity levels and onset times, suggesting that lithium may temporarily destabilize activity patterns in a way that could promote healthier rhythms in the long term. This increase in volatility was consistent across all weeks of treatment and was statistically significant.
Additionally, lithium treatment led to a significant advancement in M10 onset times, with the lithium group showing a 1.5- and 1.6-hour earlier M10 onset compared to the placebo group by weeks 3 and 4, respectively. This shift indicates that lithium may help realign circadian rhythms, promoting earlier activity onset, which is often associated with healthier sleep-wake cycles.
The study also examined the impact of lithium on circadian rhythm variability. While intradaily variability (IV) was unaffected by lithium, there was a significant increase in interdaily stability (IS) by week 4. This suggests that while lithium may introduce short-term variability in activity patterns, it also fosters long-term stabilization, possibly improving the alignment of circadian rhythms.
Interestingly, the reduction in M10 levels did not correlate with the increased volatility in M10 activity, and the advancement of M10 onset time was not related to the increased volatility in onset time. These findings suggest that lithium may alter circadian rhythms through multiple mechanisms, some of which may not directly align with immediate changes in activity levels.
The study provides compelling evidence that lithium can influence circadian rhythms in BD patients, particularly in terms of advancing activity onset times and increasing variability in activity patterns. This adaptive destabilization of circadian rhythms may help individuals with BD transition to more stable and healthier patterns of rest-activity.
These findings may offer new insights into how lithium works to stabilize mood and improve circadian rhythm disruptions in BD. By understanding how lithium affects circadian rest-activity, clinicians may be able to better predict treatment responses and tailor interventions to individual needs. Further research is needed to explore the long-term effects of lithium on circadian rhythms and its broader implications for managing BD.
You Might Be Interested In:
-
Music Therapy Intervention Improves Mental Health for Heart Failure and COPD Patients
-
Nature-Based Activities Improve Mental Health in Just Twelve Weeks
-
Qualified Midwifery Care Reduces Medical Interventions During Childbirth
