Bipolar disorder - the clue may be in the genes

May 9 2007

The first scan of the entire human genetic code has revealed that developing bipolar disorder may to some extent depend on the combined effects of variations in many different genes in the brain, none of which is powerful enough to cause the disease by itself.

The revelation by scientists at the National Institutes of Health's National Institute of Mental Health (NIMH) may help discover a new treatment.

Bipolar disorder or manic depression affects one in every 100 people and usually occurs in young adults.

Bipolar disorder causes dramatic mood swing, from overly "high" and/or irritable, to sad and hopeless, and then back again, often with periods of normal mood in between.

Severe changes in energy and behaviour go along with these changes in mood.

The periods of highs and lows are called episodes of mania and depression and these extreme changes in mood and behaviour are often very hard for others to deal with and very disabling for the sufferers.

Sufferers are easily distracted, become obsessed with grandiose plans or sink into a torpor where they can find no energy or enthusiasm for even the most simple tasks.

The condition is treated with mood-stabilising medications such as Lithium but there is a need for more effective drugs.

The scientists believe that by targeting the enzyme produced by one of these genes new and more effective medications may be developed.

The study by Dr. Amber Baum and Dr. Francis McMahon and colleagues is the first genome-wide look at genes involved in bipolar disorder and the researchers say one of the genes linked to the disorder, DGKH, is active in a biochemical pathway through which lithium is thought to exert its effects.

DGKH produces an enzyme called diacylglycerol kinase eta and the scientists believe more effective medications can be produced which act on DGKH may regulate how much of the enzyme is produced.

Other genes too produce proteins involved in this and other biochemical processes thought to play a role in bipolar disorder and 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.

For the 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.

The genetic material of each group was pooled and each group was then scanned and the researchers then focused on the gene variations which occurred more often in the people with bipolar disorder and studied them individually.

The research is published in the current issue of the journal Molecular Psychiatry.