Body and brain: possible link between inflammation and bipolar disorder.

Bipolar disorder scrawls a molecular John Hancock across the brains of some people. The signature is sometimes visible even before symptoms start, researchers in the Netherlands report.

A team led by Hemmo Drexhage, a clinical immunologist at Erasmus Medical Center in Rotterdam, found that certain white blood cells, called monocytes, pump up activity of various genes in people who have bipolar disorder. Many of the genes are involved in inflammation as well as cell movement, cell death or survival, and a pathway that allows cells to respond to chemicals that promote cell growth.

The signature of elevated gene activity in monocytes could help diagnose and classify bipolar disorder and other psychiatric disorders. Published in the April issue of Archives of General Psychiatry, the discovery also suggests that anti-inflammatory drugs could help treat the disorders.

Monocytes and other white blood cells called macrophages help fight infections and clean up dead and dying cells from injury sites.

"Everywhere in your body you have these cells, but they're not just lying around waiting for bugs to come around," Drexhage says.

The cells are involved in inducing fever. They also play an important role in the brain. They are some of the cells that make up the microglia, which are support cells for neurons. Microglial cells help regulate the brain's chemical communication system, as well as neuron growth and the formation of connections between neurons.

Drexhage became interested in the link between inflammation and psychiatric illnesses when he learned that people with bipolar disorder have a three times greater than average chance of developing autoimmune thyroid disease, an inflammatory disorder. Other data suggest that the risk for type I diabetes and some other inflammatory diseases may also be elevated in people with psychiatric disease.

"It's not just a disease of the brain, it affects the entire system," Drexhage says.

His team isolated monocytes from mentally healthy people and from people with bipolar disorder. Activity levels of 19 genes were altered in people with bipolar disorder. Twenty-three of 42 people (55 percent) with bipolar disorder carried the signature alterations, while only seven of 38 healthy people (18 percent) did.

Children of bipolar patients also bore the disorder's signature more often than did offspring of healthy people, even before symptoms of the disorder were apparent. During the course of the study, three of the children of people with bipolar disorder developed depression. All of them carried the bipolar signature in their monocytes before they developed the illness. The bipolar markers were also found in 85 percent of the children who already had mood disorders when the study started, compared with 45 percent of children without mood disorders. Only 19 percent of the offspring of healthy parents carried the signature.

Lithium, a drug commonly used to treat bipolar disorder, brought activity levels of inflammatory genes down. But that's probably not the only effect the drug has on the brain, says Robert Yolken, director of the Stanley Neurovirology Laboratory at Johns Hopkins School of Medicine in Baltimore. Researchers need to develop a better picture of how the activity of inflammatory genes varies among the population before the signature recognized in the Dutch study can be used for widespread screening and diagnosis, Yolken says.