Gene Discovery May Offer Clues on Depression and Treatment

Scientists have identified a variation in a gene that may significantly raise the risk for depression and possibly inhibit the effectiveness of a widely used class of antidepressants that includes Prozac, Paxil and Zoloft.

The finding was reported by a group of scientists at Duke University Medical Center who were investigating a recently identified gene, tryptophan hydroxylase-2, or TPH2, that is key in making the brain chemical serotonin.

Serotonin is needed for communication between certain nerves. Low levels of the chemical in the brain have been linked to depression.

Senior author Marc Caron, a Duke professor of cell biology, and colleagues identified a version of the TPH2 gene that made far less serotonin than normal.

In a group of 87 patients with major depression, they found that nine patients carried this gene variant, according to their report published online Thursday in the journal Neuron.

Within a group of 219 people who were not depressed, about 1% carried the variant.

The scientists also noted that all nine depressed patients with the gene variant responded poorly, or not at all, to the class of antidepressant drugs known as selective serotonin reuptake inhibitors.

These drugs keep serotonin levels higher between nerve cells so that better nerve-to-nerve communication can take place.

The finding was received with guarded enthusiasm by some psychiatrists.

Dr. Thomas Insel, director of the National Institute of Mental Health in Bethesda, Md., termed the findings exciting, but said he would want to see them replicated.

Because of the complexity of behavior, scientists have found it especially difficult to forge solid links between genes and mental illness, and many such links have failed to stand the test of time.

If the gene link is substantiated, scientists said, it would help shed some light on the causes of depression.

It could also help refine the tricky process of selecting the right drugs for depressed patients.

Patients’ reactions to different antidepressants vary widely, and they often must try one drug after another until a fit is found.

“This is a major issue,” said Dr. Andrew Leuchter, a professor of psychiatry at UCLA’s Neuropsychiatric Institute who was not involved in the research. “There is no practical clinical way right now to predict who is going to respond to which treatment.”

Since the gene variant was present in only 10% of the patients studied, it does not provide a blanket explanation for depression, which is estimated by the government to affect 19 million adults in the U.S. each year.

Another gene, called the serotonin transporter gene, has been linked to a tendency toward developing depression in times of stress.

In addition, environmental causes that have nothing to do with genetics are likely to play significant roles.