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Study Suggests Bipolar Disorder Linked To Genes

August 18, 2008

Researchers said on Sunday that two genes influencing 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.

The findings could help unravel the mystery of how depression arises and lead to better treatments.

The genomes of 10,596 people mainly from Britain and the United States, including 4,387 with bipolar disorder were examined throughout numerous studies by an international team of scientists.

Those with bipolar disorder were found more likely to have certain variants of the ANK3 and CACNA1C genes, researchers said. 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.

Nick Craddock of Britain’s Cardiff University, who helped lead the study, said this discovery gives scientists 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,” Craddock said.

Scientists have been trying to pinpoint family genes involved in bipolar disorder. Craddock said this was the largest genetic analysis of its kind on the disease, which affects an estimated 1 percent to 3 percent of adults worldwide.

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.

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

“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.

Bipolar disorder may stem at least in part from malfunctions in the flow of these ions, which are electrically charged versions of the chemicals, according to findings from the research.

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

Dr. Thomas Insel, director of the NIH’s National Institute of Mental Health, said the findings might 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.

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, Craddock said.

The U.S. government’s National Institutes of Health helped fund the research; it is reported in the journal Nature Genetics.

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