Researchers Find First Strong Genetic Risk Factor for Bipolar Disorder

The main treatment for bipolar disorder, lithium, was approved a half-century ago but doesn't help all patients and has significant side effects. Little progress has been made in finding better therapies, in part because scientists don’t fully understand how the condition arises or exactly how lithium improves symptoms when it does work. A genetic study involving thousands of people with bipolar disorder has revealed new insight into the condition’s molecular underpinnings. Led by scientists at the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard who collaborated with colleagues around the globe, the effort pinpoints a gene called AKAP11 (for A-kinase anchoring protein 11) as a strong risk factor for both bipolar disorder and schizophrenia. The findings may provide clues to how lithium works, as the AKAP-11 protein is known to interact with a molecular pathway modified by the drug. While many common genetic variants of small effects have been discovered, AKAP11 is the first gene found to have a large effect on bipolar disorder risk. This result has already kicked off new research at the Broad to further study the disorder in cells and animals, with a focus on molecular mechanisms that can, in turn, lead to identification of biomarkers to match patients with treatments and develop novel therapies.

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