Bipolar disorder linked to genetic traits

Two genes that influence the activity of nerve cells in the brain may play a key role in a person's risk for bipolar disorder, marked by dramatic swings from depression to manic behavior, researchers said on Sunday.

The findings are not expected to lead to a genetic test for the risk of the condition but could help unravel the mystery of how it arises and lead to better treatments, they reported in the journal Nature Genetics.

An international team of scientists examined the genomes of 10,596 people mainly from Britain and the United States, including 4,387 with bipolar disorder, also sometimes known as manic-depression.

The researchers found those with bipolar disorder more likely to have certain variants of the ANK3 and CACNA1C genes. Proteins made by the two genes help govern the flow of sodium and calcium ions into and out of neurons in the brain, influencing the activity of these nerve cells.

"The key importance of this is that it gives us a clear idea of the sorts of chemicals and mechanisms in the brain that are involved in bipolar disorder," Nick Craddock of Britain's Cardiff University, who helped lead the study, said in a telephone interview.

"Over a number of years, that will help researchers to develop better approaches to diagnosis and treatment."

Because it tends to run in families, scientists have been trying to pinpoint genes involved in bipolar disorder. This was the largest genetic analysis of its kind on the disease, which affects an estimated 1 percent to 3 percent of adults worldwide, Craddock said.

The brain disorder causes extreme shifts in mood, energy and ability to function. It is marked by high periods of elation or irritability and low periods of sadness and hopelessness that can last months.

EQUILIBRIUM

The proper function of brain neurons depends on a delicate equilibrium between sodium and calcium, the researchers said.

"The brain operates according to how quickly calcium and sodium are going in and out of cells and how much of it goes in and out," Craddock said.

The findings suggest that bipolar disorder may stem at least in part from malfunctions in the flow of these ions, which are electrically charged versions of the chemicals.

There is a need for better treatment, Craddock said. Lithium, the most common, helps only about two-thirds of those with the disorder and can cause drowsiness, weight gain and mild shakiness.

The U.S. government's National Institutes of Health helped fund the research. Dr. Thomas Insel, director of the NIH's National Institute of Mental Health, said the findings may help solve the puzzle that is bipolar disorder.

"It's not going to tell us the whole story -- it doesn't give you the whole puzzle -- but it's something to build on," Insel said in a telephone interview.

Craddock said identifying the two gene variants probably will not be helpful in determining an individual's risk for the disorder because many who do not have the disease will have the genes.

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