Gene Mutation Linked to Risk of Depression

A newly discovered gene mutation may make some people more vulnerable to depression.

If confirmed by larger studies, the finding may shed new light on depression (search), which affects almost 19 million Americans per year, according to the National Institute of Mental Health.

Several gene mutations have been linked to depression before now. The mental illness may be caused by a complex mix of genetic and environmental factors. But depression is considered to be highly treatable for people seeking help.

The latest mutation was identified by scientists at the Duke University Medical Center. Marc Caron, PhD, and James B. Duke, professor of cell biology, led the study. It appears in the online edition of the journal Neuron.

Finding the gene glitch took detective work, but Caron’s team had a good lead.

Earlier this year, they noticed that variations of a certain enzyme called tryptophan hydroxylase-2 (TPH2) (search) affected serotonin levels in mice. Serotonin is a brain chemical vital for healthy mental function. When serotonin levels are low, communication among brain cells suffers. The problem has been linked to depression and other mental illnesses such as anxiety.

With that in mind, the researchers screened the genes of 48 people from another Duke study, searching for mutations that explain TPH2’s variations. They succeeded, spotting a gene mutation that single-handedly alters TPH2.

Next, the normal and altered enzymes were tested in a lab. The mutation resulted in drastically less serotonin production. Serotonin levels were about 80 percent lower when the mutation was present.

Finally, the researchers traced the mutation among people with depression. They studied the genes of 87 people with major depression and found that more than 10 percent (nine people) carried the mutation. In people without depression, only 1 percent of people carried the mutation.

The mutation was not found among people diagnosed with bipolar disorder.

Of the nine people with the mutation, seven had a family history of mental illness or drug/alcohol abuse, six had tried to commit suicide or shown suicidal behavior, and four had generalized anxiety symptoms.

The nine participants also had a hard time taking depression medications called selective serotonin reuptake inhibitors (SSRIs), such as Prozac. They either got no relief from SSRIs or needed the strongest dose to benefit.

People who carried the mutation but had no history of major depression had some psychological symptoms. One showed signs of generalized anxiety, and the other two had mild depression and family histories of mental illness or drug and alcohol abuse.

Larger genetic studies are needed to learn more about the mutation, say the researchers. They also want to see if it affects other conditions such as generalized anxiety disorders, suicide, drug abuse, and autism.

By Miranda Hitti, reviewed by Brunilda Nazario, MD

SOURCES: Zhang, X. Neuron, online edition, Dec. 9, 2004. National Institute of Mental Health: “Depression.” WebMD Medical News: “Gene Doubles Risk of Depression in Some.” WebMD Medical News: “Depression: Genetic or Environmental?” News release, Duke University.