The likelihood of developing bipolar disorder depends on the variations in many different genes in the brain, none of which is powerful enough to cause the disease by itself, a new study shows. But the discovery could lead to effective new treatments, according to researchers from the US.

Bipolar disorder, also sometimes called manic-depressive illness, involves experiencing extremes in mood, swinging suddenly between elated, chaotic over-excitement and a depression so severe that it hinders the ability to work and function. It affects about one per cent of the population in the UK, and happens to both men and women of any age – in fact, it’s often most extreme in children. Four out of five sufferers will have at least one more bipolar episode after their first.

The condition is usually stabilised using mood medications like lithium. But some people do not respond to these medications, and doctors need more options so that they can tailor treatments to each patient.

Now, targeting the enzyme produced by one of the newly-discovered bipolar-prompting genes in the brain could lead to the development of new, more effective medications.

People inherit different gene variations, which may influence whether or not they respond to a given medication. Identifying and targeting these variations could help scientists develop additional medication options that take these differences into account.

"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,” said study director Dr Elias A. Zerhouni. “We now have a new molecular target scientists can investigate in their search for better medications for bipolar disorder."

One of the genes the researchers correlated with the disorder, DGKH, is active in the same area through which lithium exerts its therapeutic effects. The gene produces an enzyme that functions at a point closer to the root 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 this enzyme or regulate how much of the enzyme is produced.

Several other genes detected in the study produce proteins involved 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 better prevented or treated.

"Treatments that target just a few of these genes or the proteins they make could yield substantial benefits for patients,” said lead researcher Dr Francis J. McMahon. “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."

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. The finding was enabled by recent genetics technology that allows researchers to scan, in a single experiment, thousands of genes for variations.

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