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The World in Medicine
September 17, 2008

Clues to Bipolar Disorder

JAMA. 2008;300(11):1291. doi:10.1001/jama.300.11.1291-d

Researchers from the United States, the United Kingdom, and Australia have linked variants in 2 genes with an increased risk of bipolar disorder (Ferreira MA et al. Nat Genet. doi:10.1038 /ng.209 [published online ahead of print August 17, 2008]). Both genes encode proteins that play roles in ion channels in nerve cells and affect the excitability of neurons.

The genome-wide association study, which tested 1.8 million variants in 4387 individuals with bipolar disorder and 6209 controls, found the strongest evidence for increased risk of the disorder for variants in 2 genes involved in the balance of sodium and calcium in cells: ANK3, which encodes a protein (ankyrin G) reported to regulate the assembly of sodium channels, and CACNA1C, which encodes a calcium channel subunit. Previous research in mice by some members of the research team had demonstrated that the drug most commonly used to treat bipolar disorder, lithium (which affects the way sodium moves through ion channels), reduces the expression of both ANK3 and subunits of the calcium channel.

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