A research team from McGill University may have uncovered a critical piece in understanding bipolar disorder: the biological cause of mood shifts between mania and depression.

While most people follow a 24-hour sleep-wake rhythm, individuals with bipolar disorder often exhibit a 48-hour cycle that aligns closely with mood episodes, shorter sleep associated with mania and longer sleep with depression.

Published in Science Advances, the study suggests that two internal biological clocks are at play in bipolar disorder. One is the familiar circadian sleep-wake cycle, and the other involves dopamine-producing neurons,  a secondary clock that appears to influence alertness and mood. While this second clock is typically inactive in healthy individuals, it may drive mood fluctuations in people with bipolar disorder when it interacts with the sleep-wake cycle.

In experiments on mice, researchers triggered this dopamine clock using methamphetamine, which led to behavior patterns mimicking manic states. When dopamine neurons in brain areas related to reward and motivation, specifically the ventral tegmental area (VTA) and nucleus accumbens (NAc), were disrupted, the abnormal rhythms ceased. Conversely, activating these neurons prolonged activity cycles, an effect reversed by antipsychotic medication.

Lead researcher Dr. Kai-Florian Storch described the phenomenon as a biological “tide” comparing the coordinated action of the two clocks to the influence of the sun and moon on ocean tides.

The study introduces a novel perspective on bipolar disorder by identifying a distinct dopamine-based rhythm generator. This opens new doors for treatment strategies focused on targeting this rhythm, potentially reducing the severity and frequency of mood episodes.

However, researchers emphasize that much remains unknown about the molecular mechanisms behind this dopamine clock, and further studies will explore the genetic and environmental triggers that may activate it in humans.