Two genes in the brain that control the activity of the nerve cells may play a big role in a person's risk for developing bipolar disorder, which is marked by dramatic swings from being depressed to manic behavior and affects between one and three percent of the population worldwide. While identifying these genes is important, it is not expected that it will lead to a genetic test for the risk of bipolar disorder. It could, however, help unravel the mystery of how it arises and could lead to better treatments.

A team of international scientists examined the genomes of approximately 10,956 people that were mainly from the United States and Britain. This was including 4,387 people with the disorder, also often known as manic-depression.

The scientists found that the people with the disorder were more likely to have certain variants of the ANK3 and CACNA1C genes. The proteins that these two genes make help govern the flow of calcium ions and sodium in and out of neurons in the brain, which in turn influences the activity of the nerve cells.

The person who helped lead the study, Nick Craddock of Britain's Cardiff University, said, "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. Over a number of years, that will help researchers to develop better approaches to diagnosis and treatment."

Because this disorder has a history of running in families, scientists have been trying to pinpoint the genes that are involved in bipolar disorder. This study was the largest genetic analysis of it kind on bipolar disorder.

This disorder of the brain can cause extreme shifts in mood, energy and general ability to function. Bipolar disorder is marked by high periods of elation or irritability which is followed by periods of sadness and hopelessness that could last for months.

The researchers stated that proper function of neurons in the brain depends on a delicate balance between of calcium and sodium. Our brains operate on how quickly sodium and calcium are moving in and out of cells and the amount that goes in and out. The findings of this study suggest that this disorder may stem at least in part from malfunctions in the flow of these ions, which are the chemicals that are electrically charged.

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

The research was funded in part by the U.S government's National Institutes of Health. The director of the NIH's National Institute of Mental Health, Dr. Thomas Insel, said that 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."

Craddock said that identifying the two gene variants will probably not be helpful in determining a person's risk for bipolar disorder because many people who do not have this disorder will have the same genes.

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