Why Depression Can Strike Again

Researchers find 'trait marker' in people recovered from depression

Physicians and patients have long known that people who have a major depressive episode have a greater risk for suffering another. These people, although ostensibly recovered, also remain unusually sensitive to emotional stress.

In a November 2002 issue of the American Journal of Psychiatry, researchers reported identifying what may be a "depression trait marker" in the brain which explains why patients who have recovered nevertheless remain vulnerable to another depressive episode.

And in a second study released around the same time, another research team says it identified the first gene that leaves women vulnerable to clinical depression.

The Return of Depression

"Depression is not a single event for many people and each episode, if you're lucky, can be treated and you can be well, but depressed patients know that they are at risk for more episodes," says Dr. Helen Mayberg, lead author of the "trait marker" study and a professor of psychiatry and neurology at the University of Toronto. "The question is what about your brain seems to be the area of vulnerability."

Previous research has already demonstrated that the brains of depressed people work in different ways than healthy people. This study takes the concept further.

It "goes to a new level because it talks about people who have recovered from depression or who have been treated. Their brains are functioning differently, and it's a question of why they're functioning differently," says Dr. Kenneth Skodnek, chairman of the department of psychiatry and psychology at Nassau University Medical Center in East Meadow, N.Y. "This is special because I believe this is the first time that there has been evidence even when someone recovers that the brain is still not functioning normally."

In this study, researchers asked 25 adults to remember an extremely sad experience in their life, then scanned their brains with positron emission tomography (PET) while they recalled the event.

The participants belonged to one of three categories: 10 women who had recovered from a major depression (nine were on medication and one was not); seven women who were at that time in the throes of a major depressive episode (only one was on antidepressant medication); and eight healthy women who had no personal or family history of depression.

The scans, which measure blood flow, showed that the brains of the recovered patients and currently depressed women experienced different changes than the brains of the healthy participants.

"We saw that recovered patients looked for all intents and purposes like acutely depressed patients and that there were some very specific areas of the brain that changed uniquely in depressed patients that we don't see in healthy subjects and vice versa," Mayberg says. "Under that emotional stressor, the recovered depressed patients looked like the worst depressed patients. When we stressed healthy subjects' brains, we didn't see any decrease in brain activity."

Specifically, the subgenual cingulate and the medial frontal cortex areas of the brain were involved. The subgenual cingulate has already been identified as being involved in the experience of intense sadness even in healthy individuals. It is also a target of antidepressant medication.

"These people are different even when they're treated," Skodnek says. "It's almost like someone comes in with congestive heart failure, you treat them" and the heart appears to be doing OK. "But if you know what's going on with the heart, it's not OK."

Whether the differences in brain function are a cause or effect of a previous depressive episode remains unknown.

Nevertheless, this research and future studies it spawns will have important implications for identifying people at risk for depression and in identifying new targets for drug therapy.

Although this appears to be a trait marker for depression, Mayberg is careful not to overstate the case. "I wouldn't want anyone to think we've got the glucose tolerance test for depression," she says.

Meanwhile, researchers at the University of Pittsburgh say they've found evidence that a gene in chromosome 2q33-35 leaves women at a higher risk for depression. However, they found no such correlation in men, suggesting that vulnerability to the disease is at least in part influenced by one's gender.

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