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 Research & Giving News Article  to Better Bipolar Treatments One of the Results of First Genome-Wide Study of Bipolar Disease Dr. McMahon and colleagues at NIMH, the Universities of Heidelberg and Bonn in Germany, and a number of U.S. facilities collaborating in a major project called the NIMH Genetics Initiative, published a study in the May 8 issue of Molecular Psychiatry based upon a comprehensive scan of human gene variants. The team’s aim was to find variations specifically associated with bipolar disorder. They determined that the likelihood of developing bipolar disorder depends in part on the combined, small effects of variations in many different genes in the brain, none of which is powerful enough to cause the disease by itself. One of the genes the researchers correlated with bipolar disorder, called DGKH, is active in a biochemical pathway through which the drug lithium is thought to exert its therapeutic effects. The gene in question produces an enzyme (diacylglycerol kinase eta) that functions at a point closer to the root of the lithium-sensitive pathway than does the protein that lithium is thought to target. Scientists can now try to develop more effective medications by focusing on new compounds that act on the DGKH enzyme or regulate how much of the enzyme is produced. The DGKH gene is on chromosome 13. Several other genes detected in the study produce proteins involved in this and other biochemical pathways that are thought to play a role in bipolar disorder. Understanding the effects that variations of these genes have on brain-cell function could lead to explanations of how they contribute to the condition and how it might be prevented or more effectively treated. "Treatments that target just a few of these genes or the proteins they make could yield substantial benefits for patients,” Dr. McMahon said. “Lithium is still the primary treatment for bipolar disorder, but DGKH is a promising target for new treatments that might be more effective and better tolerated.” The research team’s finding was enabled by recent genetics technology that allows researchers to scan, in a single experiment, thousands of genes for variations. Everyone has the same genes, but variations in them influence whether or not a person gets a specific disease. In this study, researchers compared variations found in the scans of 413 adults who had bipolar disorder with variations found in the scans of 563 healthy adults. An important issue in genetics research is that findings correlating specific genes with specific diseases in one population may not apply to other populations. This study addressed that issue by focusing on American participants of European ancestry, then repeating the study in a large group of patients in Germany. Similar outcomes were found in both populations, strengthening the case for the validity of the results. A subsequent study is examining whether the results apply to other populations, and will look for common variations among them. "This is an example of how advances in genetics research feed into practical applications. This research would not have been possible a very few years ago. We now have a new molecular target scientists can investigate in their search for better medications for bipolar disorder," said NIH Director Elias A. Zerhouni, M.D. About 5.7 million American adults have bipolar disorder, which also is called manic-depressive illness. Children also may have the condition, usually in a more severe form than adults. "We're beginning to get a foothold on the genetics of this complex brain disorder," commented Thomas R. Insel, M.D., the Director of the NIMH and a member of NARSAD’s Scientific Council. |
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