Circadian Rhythm Linked to Bipolar Disorder

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Almost all people suffering from this disorder also have irregularities in circadian functions including sleep/wake, hormonal, appetite and body temperature. Major disruptions in the sleep/wake cycle can trigger a bipolar episode. And many of the treatments for bipolar disorder, such as lithium, can shift circadian rhythms.

There has been some indication that the CLOCK gene, one of the most important genes involved in circadian rhythm, might also be implicated in the disorder. But the evidence hasn't been definitive.

"I think the connection has always been there, but most of the studies were correlative," Earnest said. "We really couldn't say that there was a definitive connection between circadian rhythm disturbances. It was just an association."

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For the new study, which appears in this week's Proceedings of the National Academy of Sciences, McClung and her colleagues tested mice that had a mutation in the CLOCK gene to see if there were similarities to humans with bipolar disorder.

Indeed, the mice exhibited hyperactivity, more risk taking, a preference for "reward" substances such as cocaine and sugar, and less depression.

And when the mice were given lithium, their behavior stabilized.

"Taken together, this whole profile of behaviors is very similar to bipolar patients when they're in a manic stage," McClung said. "This is really important, because there hasn't been a good or complete model of human mania. This is the most complete model ever described."

The researchers went one step further to try to determine what part of the brain was involved. When they put a functional clock gene back into the dopamine cells of the mice (dopamine is involved in reward and mood regulation), they found this also corrected some of the manic behaviors.

"This is exciting, because it pinpoints the area of the brain where CLOCK is functioning," McClung said. "We really didn't know what CLOCK was doing there. It looks like CLOCK is regulating dopamine activities, and that could be what's causing these types of behaviors."

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