Genetic Roots Of Bipolar Disorder Revealed

The genetic roots of bipolar disorder – manic depression – have been revealed by the first scan of the entire human genetic code, revealing a new target for treatments. Bipolar disorder affects one person in every 100 inducing mood changes from extremes of depression to irritation, elation and mania.

However, the likelihood of developing the disorder, which usually occurs in young adults, 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, a new study shows.

However, targeting the enzyme produced by one of these genes could lead to development of new and more effective medications, according to the study by scientists at the National Institutes of Health’s National Institute of Mental Health, NIMH, with others from the Universities of Heidelberg and Bonn and a number of American labs collaborating in the NIMH Genetics Initiative.

The study is the first to scan virtually all of the variations in human genes – more than half a million genetic variations – to find those associated with this disorder and is published toda y in the journal Molecular Psychiatry by Dr Amber Baum, lead researcher Dr Francis McMahon and colleagues. “This is only the first genome-wide look at genes involved in bipolar disorder”, Dr McMahon told The Daily Telegraph.

Most people have mood swings now and again but the shifts which occur with bipolar disorder, and the changes in behaviour and energy level which accompany them, are sometimes disabling, as sufferers are easily distracted, become obsessed with grandiose plans or sink into torpor. Lithium and the other mood-stabilising medications help many of them but there is still a need for better drugs.

One of the genes the researchers correlated with the disorder, DGKH, is active in a biochemical pathway through which lithium is thought to exert its effects. The gene produces an enzyme called diacylglycerol kinase eta which is different from the protein which lithium is thought to target. Scientists can now try to develop more effective medications by focusing on new compounds which act on the DGKH enzyme or regulate how much of the enzyme is produced.

Several other genes detected in the study produce proteins involved in this and other biochemical processes thought to play a role in bipolar disorder. Understanding the effects which variations of these genes have on the workings of brain cells 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. 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,” Dr McMahon said.

The finding was enabled by recent genetics technology which allows researchers to scan, in a single experiment, thousands of genes for variations. Everyone has the same genes but variations in them can influence whether or not a person gets a specific disease. In this study, researchers compared variations found in the scans of 1091 adults who had bipolar disorder with variations found in the scans of 1106 healthy adults.

By pooling the genetic material of the adults with bipolar disorder, the researchers were able to scan the entire group at a small fraction of the cost of scanning each person’s material individually. The genetic material of the healthy group was pooled and scanned separately, again at a fraction of the cost of individual scans. The researchers then zeroed in on the gene variations which occurred more often in the people with bipolar disorder and studied them individually.