Researchers at McGill University have made a breakthrough in understanding what causes mood shifts in bipolar disorder. Their study reveals that two internal biological clocks drive the alternating manic and depressed states in people with the condition.
Normally, adults have a 24-hour sleep-wake rhythm. But in bipolar disorder, some patients show a 48-hour cycle that matches their mood changes. Short sleep days are often linked to mania, while long sleep days are connected to depression.
The McGill team discovered that one clock follows the usual sleep-wake cycle. The second clock is controlled by dopamine-producing neurons, which affect alertness. This dopamine-based clock is usually inactive in healthy people but appears to influence mood swings in bipolar patients, depending on how it aligns with the sleep-wake clock.
In experiments with mice, the researchers activated the dopamine clock and observed mood-like behavioral rhythms similar to those seen in bipolar disorder. When they disrupted dopamine neurons in the brain’s reward center, these mood cycles stopped, showing that dopamine neurons play a key role.
Mice given methamphetamine in their water developed activity cycles lasting 48 hours or more, mimicking manic behavior. Disrupting dopamine neurons in specific brain regions—the ventral tegmental area (VTA) and the nucleus accumbens (NAc)—stopped these cycles. Activating these neurons extended the activity cycles, but this effect was reversed by antipsychotic drugs. The VTA and NAc form the mesolimbic pathway, a crucial circuit for motivation and reward.
Lead author Dr. Kai-Florian Storch, an Associate Professor at McGill’s Department of Psychiatry, explained, “Our model offers the first universal mechanism for mood switching, similar to how the sun and moon control spring tides at specific times.”
Current bipolar disorder treatments stabilize mood but do not target the underlying causes of mood swings. Dr. Storch said, “Our discovery points to a new treatment approach aimed at correcting or silencing this dopamine clock to reduce mood episodes.”
Although the detailed molecular workings of this dopamine clock are still unknown, the research team plans to study its physiological mechanisms further. They also aim to explore genetic and environmental factors that might activate this clock in humans.
This study brings hope for improved treatments targeting the root causes of bipolar disorder, potentially leading to better mood stability and quality of life for patients.
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