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The study, led by McGill University and published in the journal Science Advances, sheds light on a breakthrough in understanding what causes the alternation between the two states—an understanding that, according to Kai-Florian Storch, the study's lead author, is considered the Holy Grail in bipolar disorder research.
"Our model defines the first universal mechanism of state alternation cycles, much like the sun and moon influence tides in a recurring and timely manner," explains the author, an associate professor in the Department of Psychiatry at McGill University and a researcher at the Douglas Hospital Research Centre.
The study's findings suggest that the regular alternation between states in bipolar individuals is determined by two "clocks": the biological one, which imposes a 24-hour cycle; and a second one, regulated by dopamine neurons responsible for alertness. Consequently, the way these clocks, with different rhythms, coordinate could explain the onset of manic and depressive states.
The authors also believe that the second clock is likely dormant in non-bipolar individuals.
As part of their study, the scientists activated the second clock in mice to create behavioral rhythms similar to the mood swings characteristic of bipolar disorder. However, when they disrupted the activity of dopamine-producing neurons in the brain's reward center of the mice, these rhythms disappeared, highlighting the key role of dopamine in mood swings in bipolar individuals.
Hope for new treatments
Currently, treatments for bipolar disorder aim to stabilize mood but generally do not address the root causes of state changes, the researchers explain.
"Our discovery of a dopamine-regulated vigilance rhythm generator opens up a new and distinct treatment target: adjusting or putting this clock on standby to reduce the frequency and intensity of mood swings," says Kai-Florian Storch.
What remains unknown, however, is the exact molecular functioning of the dopamine-regulated clock and the genetic and environmental factors that can activate it in humans. The research team will therefore focus on these triggers and molecular mechanisms.
This study was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, and the Graham-Boeckh Foundation.
Reference:
The study "Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state," by Kai-Florian Storch et al., was published in the journal Science Advances.