Harvard Mental Health Letter

Commentary: The Clock gene and bipolar disorder

Commentary

The Clock gene and bipolar disorder

A mutant strain of mice may help us to understand the origins of the manic phase of bipolar disorder. Researchers studied mice with a variant form of the Clock gene, which is instrumental for regulating their circadian (daily, or 24-hour) physiological rhythms. Mice that carry this mutant gene have symptoms that resemble human mania, and these symptoms can be eliminated if they are given lithium. The authors of the study, published in April in the Proceedings of the National Academy of Sciences, believe that this animal model of mania will help scientists develop better treatments.

People with bipolar disorder tend to have irregular circadian cycles. The symptoms of mania include disturbances in the daily rhythms of sleeping and waking, energy levels, appetite, and hormone production. In some individuals, mood changes with the seasons — depression in winter and mania in summer. Clinicians often tell bipolar patients that if they want to reduce the risk of a manic or depressive episode, they should stick to a regular schedule, including plenty of sleep.

Internal biological clocks are basic to life. The human version resembles the ones found in mice, fruit flies, and even bread mold. Researchers have begun to understand that these clocks are genetically controlled by means of a feedback loop. A group of genes is activated, starting a process that ends in the production of proteins. When the concentration of the proteins reaches a certain level, the genes turn off, and protein levels decrease to the point where production begins again. This cycle takes about 24 hours in humans.

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