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Circadian Clocks May Hold Key to Treatment of Bipolar Disorder
Scientists have gained insight into why lithium salts are effective at treating bipolar disorder in what could lead to more targeted therapies with fewer side effects. Bipolar disorder is characterized by alternating states of elevated mood, or mania, and depression. It affects between 1% and 3% of the general population. The extreme 'mood swings' in bipolar disorder have been strongly associated with disruptions in circadian rhythms – the 24-hourly rhythms controlled by our body clocks that govern our day and night activity. For the last 60 years, lithium salt (lithium chloride) has been the mainstay treatment for bipolar disorder, but little research has been carried out to determine whether and how lithium impacts the brain and peripheral body clockwork. "Our study has shown a new and potent effect of lithium in increasing the amplitude, or strength, of the clock rhythms, revealing a novel link between the classic mood-stabilizer, bipolar disorder, and body clocks," said lead researcher Dr. Qing-Jun Meng, in the University of Manchester's Faculty of Life Sciences. "By tracking the dynamics of a key clock protein, we discovered that lithium increased the strength of the clockwork in cells up to three-fold by blocking the actions of an enzyme called glycogen synthase kinase or GSK3. Our findings are important for two reasons: firstly, they offer a novel explanation as to how lithium may be able to stabilize mood swings in bipolar patients; secondly, they open up opportunities to develop new drugs for bipolar disorder that mimic and even enhance the effect lithium has on GSK3 without the side effects lithium salts can cause." These side effects include nausea, acne, thirstiness, muscle weakness, tremor, sedation, and/or confusion.