New Depression Studies Reveal Persistent Serotonin System Abnormality In Patients

They found that depressed people showed a blunted hormonal response to a test he developed that boosts serotonin, an important neurotransmitter chemical in the brain.

"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."

Now, newly published work by his laboratory shows that as a group, people suffering from the illness 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."

Golden is professor and chair of psychiatry at the UNC School of Medicine. In February next year, he will receive the American College of Psychiatrists’ annual award for contributions to mood disorders research.

A report on the findings appears in the May issue of Neuropsychopharmacology, a scientific journal. Besides Golden, authors include biostatistician R. David Ekstrom, Drs. Joseph M. Bebchuk and Martha E. Leatherman, both former postdoctoral fellows, and Dr. James C. Garbutt, professor of psychiatry.

One of the body’s most important neurotransmitters, serotonin helps regulate many emotional and physiologic functions that are disturbed when people suffer from depression, Golden said.

With the help of 20 affected patients -- plus non-depressed "control" subjects -- the UNC team measured changes in levels of prolactin and several other hormones released by the pituitary gland at the base of the brain in response to the serotonin challenge test. Their goal was to learn whether the abnormality was always present or detectable only when patients were depressed and disappeared like fevers do when infections end.

They then treated the patients and tested them again at the end of acute therapy, at the end of a year and a fourth time a month or so after they completed their treatments.

"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 out of the blue, he said. Although more common in women than in men, depression can strike anyone from old people to children and at any time in life.

"This is a dangerous illness because it is linked to suicide as well as to considerable suffering in relationships at home, at school and at work."