Circadian rhythm gene linked to bipolar disorder 19/3/07. By UT Southwestern Medical Center Disrupt the gene that regulates biological clocks in mice and they become manic, exhibiting behaviours similar to humans with bipolar disorder.

Scientists from UT Southwestern have found that the Clock gene, which controls the body's circadian rhythms, may be integrally involved in the development of bipolar disorder.

"There's evidence suggesting that circadian genes may be involved in bipolar disorder," said Dr. Colleen McClung, assistant professor of psychiatry and the study's senior author. "What we've done is taken earlier findings a step further by engineering a mutant mouse model displaying an overall profile that is strikingly similar to human mania, which will give us the opportunity to study why people develop mania or bipolar disorder and how they can be treated."

The study was published in the 'Proceedings of the National Academy of Sciences'.

Circadian rhythms include the daily ups-and-downs of waking, eating and other processes such as body temperature, hormone levels, blood pressure and heart activity.

Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes dramatic shifts in a person's mood, energy and ability to function – much more severe than the normal ups and downs that most people experience.

The study included putting the mutant mice through a series of tests, during which they displayed hyperactivity, decreased sleep, decreased anxiety levels, a greater willingness to engage in ‘risky’ activities, lower levels of depression-like behaviour and increased sensitivity to the rewarding effects of substances such as cocaine and sugar.

"These behaviours correlate with the sense of euphoria and mania that bipolar patients experience," said Dr McClung. "In addition, there is a very high co-morbidity between drug usage and bipolar disorder, especially when patients are in the manic state."

During the study, lithium was given to the mutant mice. Lithium, a mood-stabilising medication, is most commonly used in humans to treat bipolar patients. Once treated with the drug on a regular basis, the majority of the study's mice reverted back to normal behavioural patterns, as do humans.

The researchers also injected a functional Clock gene protein into a specific region of the brain that controls reward functions and where dopamine cells are located. Dopamine is a neurotransmitter associated with the ‘pleasure system’ of the brain and is released by naturally rewarding experiences such as food, sex and the use of certain drugs. This also resulted in the mice going back to normal behaviours.

"While the Clock gene is expressed throughout the brain, it's really only been studied in one particular brain region, which is the one that's involved in circadian rhythms," said Dr McClung. "This is one of the first studies to show that Clock has a major effect on behaviour in a different brain region – specifically the one that controls reward responses and mood."

Adapted from a news release by UT Southwestern Medical Center .

Image credit: Rowena Dugdale

Further reading

Roybal K, et al. Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci USA 2007;104(15):6406-11. Epub 2007 Mar 22. Abstract