"This neuroendocrine challenge test, which involved giving depressed volunteer patients a medicine called clomipramine, indicated that depressed patients' serotonin systems were sluggish in response and not working efficiently," Golden said. "An analogy I use is that their serotonin 'engine' needs a tune-up because they aren't getting much mileage out of the gas being burned."

The current research shows that, as a group, people suffering from depression have that biological abnormality even when they are not depressed.

"We believe this work is an important step forward in our understanding of depression because it demonstrates an ongoing trait that distinguishes patients who have had the illness from the rest of the population," he said. "It is strong evidence that depression reflects a genetic trait, which clinicians have believed for a long time because depression tends to run in families."

Researchers enlisted 20 patients with clinical depression and 20 non-depressed control subjects; they measured changes in levels of prolactin and several other hormones released by the pituitary gland in response to the serotonin challenge test. The patients were then treated and tested again at the end of acute therapy, at the end of a year, and a fourth time one month or so after completion of treatment.

"To our surprise, in that medication-free state of remission, most of them still demonstrated a blunted hormonal response to serotonin challenge," Golden said. "That means that even when they are well, their serotonin systems still do not work as efficiently as in people who don't have a history of depression. It may also mean that those patients with this persistent abnormality need to stay on medication longer."

Golden and colleagues now are trying to identify specific genetic components of the serotonin system that may account for their findings. Besides current patients, they also are studying former victims of depression and first-degree relatives to learn more about the condition's genetic intricacies.

"Certainly there won't be any one single genetic basis for depression, but instead multiple genetic vulnerabilities that can increase the chances of depression emerging," the physician said.

Depression affects about 10 percent of the U.S. population at some point in life, he said. Upsetting events such as the death of a loved one, loss of a job or stress can trigger it, or it can occur without an apparent trigger, he said. Although depression is more common in women than in men, it can strike at any time in life.