2 Genes May Be Linked to Bipolar Disorder

Two abnormal genes may have a role in bipolar disorder, a new study finds. Researchers pooled genetic data from several sources. They included a total of 10,596 people. Of these, 4,387 had bipolar disorder. Variant forms of two genes were most likely to be found in people with bipolar disorder. These genes build parts of channels that manage the flow of sodium and calcium to and from nerve cells. Drugs now used to treat bipolar disorder are believed to target these channels. The study was published online August 17 by the journal Nature Genetics.

What Is the Doctor's Reaction?

Bipolar disorder causes symptoms of a psychiatric disease. But new science suggests that its roots are astonishingly biological.

Bipolar disorder is a type of depression that causes extreme mood swings. At times, the person is severely depressed. "Manic" episodes are quite different. The person will be very excited, active or irritable. Behavior is not practical and can be embarrassing. Coping with this can be quite a challenge.

This condition is also called bipolar affective disorder or manic depression.

Bipolar disorder can run in families. Thus, doctors guessed many years ago that genetics might be behind this disease. Now, gene studies are confirming this theory. Scientists are identifying genes linked to bipolar illness. In the process, they are unlocking a large part of the mystery behind the disease.

The largest genetic study ever done on bipolar disorder was just released this week. It was funded by the National Institutes of Health (NIH).

The study found two genes to be closely associated with bipolar disorder. Both of the genes affect the way our bodies build structures called "ion channels" on the surface of nerve cells. Ion channels are the gates used by charged particles as they surge in and out of cells. Sodium and calcium are two of these ions.

Opening and closing of ion channels is what causes a nerve cell to "fire." This means that it sends an electrical signal to the next cell. Problems can occur in this process. Nerve cells may not fire easily. Or they may be "excitable" and fire too easily. These problems can lead to unhelpful patterns of brain signaling. Unstable nerve activity probably is what causes the symptoms of bipolar disorder.

How did the study make a connection between the genes and bipolar disease? Researchers combined gene data that had been collected in smaller studies. This allowed them to compare the genes of two large groups of people. One group had bipolar disorder. The other did not. Altogether, the genes of more than 10,000 people were analyzed. Almost half had bipolar disorder. Comparing these groups let scientists see what gene variations were closely linked with bipolar disease.

Scientists have already begun to talk about bipolar disorder using "biological" terms. In fact, the researchers on this gene study invented a new term to help describe the biology behind the disease. Bipolar, they said, is an "ion channelopathy." An illness that ends in "opathy" always has a biological origin.

What Changes Can I Make Now?

With an improved understanding of bipolar disease, we learn an important lesson. We learn that there are good reasons some drugs treat bipolar disorder better than others.

For bipolar disease, the best ("first line") treatments are known as mood stabilizers. The most famous and most helpful of these medicines is lithium. This is a salt, similar to other sodium salts. Lithium affects the way that sodium travels through ion channels.

Many of the other mood stabilizers used to treat bipolar disorder help to prevent nerves from firing in unpredictable ways. Examples are valproic acid (Depakote), carbamazepine (Tegretol), and lamotrigine (Lamictal). These drugs first were used to control or prevent seizures in people who have epilepsy.

Standard antidepressant drugs appear to add little to treatment for bipolar disorder. A study published in March 2007 randomly assigned bipolar patients who were taking mood stabilizers to add another daily drug. People were divided into three groups. Two groups received an antidepressant. The third received placebo (fake) pills. All of the groups had the same rate of recovery from depression symptoms during the six-month study. The antidepressants also made no difference in symptoms of mania. About 10% of each group had these symptoms during the study.

If you have bipolar disorder, make sure that you are being treated with a mood stabilizer. Traditional antidepressant drugs are less likely to help you. They may not add an obvious benefit even if they are combined with a mood stabilizer.

What Can I Expect Looking to the Future?

Knowing that ion channels are important to bipolar disorder will help scientists to tailor their efforts in drug development. During the next decade or two, the biology of bipolar disease is likely to allow major advances in treatment.