New Study Unveils Dopamine-Driven Brain Clock behind Mood Swings in Bipolar Disorder
McGill University researchers discovered a new mechanism that could explain the irregular mood swings associated with bipolar disorder. The study, which was published in Science Advances, shows that these changes are caused in large part by a second brain clock controlled by neurones that make dopamine. This finding opens up exciting new therapeutic options.
The study, directed by Kai-Florian Storch, Associate Professor of Psychiatry at McGill and researcher at the Douglas Research Centre, sheds light on how bipolar individuals experience alternating episodes of mania and despair. According to Storch, determining the origin of these shifts has long been a significant barrier in understanding the illness.
"Our model offers the first universal mechanism for mood switching or cycling, which operates analogously to the sun and the moon driving spring tides at specific, recurring times," Storch stated.
The researchers argue that mood variations in bipolar disorder are regulated by two clocks: the well-known biological 24-hour circadian clock and a dopamine-driven clock. This secondary clock, which is generally dormant in healthy people, controls arousal and alertness. The interplay between these two clocks, which run at different speeds, appears to determine whether a person is manic or depressed.
In their experiments, the team stimulated the mice's dopamine-based clocks, causing behavioural rhythms similar to bipolar disorder mood swings. Disruption of dopamine-producing neurones in the brain's reward centre stopped these rhythms, indicating the fundamental role of dopamine in the phenomenon.
Current therapies for bipolar disorders largely aim to stabilise mood using drugs such as lithium or antipsychotics, but they frequently fail to address the underlying reasons for mood swings. The development of this dopamine-based clock provides new therapeutic options that target the underlying mechanism.
"Our discovery provides a novel and distinct target for treatment, which should aim to correct or silence this clock to reduce the frequency and intensity of mood episodes," Storch stated.
In the future, treatments might focus on turning off genes or using drugs to manage the dopamine-based arousal rhythm generator. However, there are still significant concerns regarding the molecular mechanisms of the clock and the genetic or environmental triggers that activate it in humans.
The team intends to dig deeper into the molecular "gears" of the dopamine clock, attempting to understand its precise mechanics and interactions with the circadian clock. Furthermore, they intend to investigate potential genetic and environmental factors that may influence the activation of this secondary clock in people.
The work also raises intriguing concerns about the role of dopamine-based rhythms in mental health diseases other than bipolar disorders, such as depression and schizophrenia.
The findings have important implications for millions of people living with bipolar disorder, which affects around 1% of the global population. Future medicines that address the underlying mechanism of mood cycling could significantly improve patients' quality of life while reducing the burden of controlling the illness.