DNA Research Gives New Insight into Treating Emotional Disorders

(HealthDay News) – The more scientists learn about human genetic structure, the more possibilities there are for treating all sorts of conditions, both physical and mental.

Two recent discoveries point to the role DNA may some day play in helping people fight depression and rebound from tragic occurrences in their lives.

The first study, published in the journal Science, involved researchers who tracked 847 people from birth to adulthood and found those with a variation in the so-called serotonin transporter gene, 5-HTT, were two-and-a-half times more likely to get depressed when they encountered serious life stresses.

The second study, which was also published in Science about six months after the first, involved a naturally-occurring genetic mutation found in mice that affects brain levels of serotonin, which is associated with depression, anxiety and other psychiatric conditions.

The discovery may help explain why some patients feel much better after taking serotonin-altering antidepressants such as Paxil, Prozac and Zoloft, and why others do not.

The 5-HTT gene helps control the neurotransmitter serotonin and comes in a short and a long version. Serotonin is the target of the newest generation of antidepressants, known as selective serotonin reuptake inhibitors. Those in the study with the short version were found to be more vulnerable to depression from life stress, says Terri Moffitt, the study's corresponding author who is a professor of psychiatry at the University of Wisconsin.

Moffitt and her colleagues concentrated on study participants who suffered multiple crises, such as job loss, a relationship breakup or a death in the family, over a five-year period. They determined the 5-HTT genetic makeup of each participant, noted the stressful life events, and then evaluated who got depressed.

Among those with the short, or stress-sensitive, variation of the gene who suffered multiple life stresses, 43 percent developed depression. But among those with the long variation, only 17 percent got depressed.

Meanwhile the serotonin mouse study findings "suggest that there really are heritable differences in how the brain makes or synthesizes serotonin," said Dr. Jerrold Rosenbaum, chief of psychiatry at Massachusetts General Hospital in Boston .

"It gives us a whole new line of inquiry, both as to tailored treatment and to understanding how treatments work, and why there are differences in the response," he said.

Serotonin is a neurotransmitter, part of the chemical circuitry of the brain responsible for putting thought, emotion and action together to shape human behavior. In healthy individuals, serotonin and another neurotransmitter, dopamine, work together in a kind of "chemical balance" to keep mood and emotions relatively stable.

When that balance is upset, however, conditions such as chronic depression can result. Medications called selective serotonin reuptake inhibitors (SSRIs) work to keep serotonin at elevated concentrations, restoring that balance and elevating mood in the process.

But for years, psychiatrists have realized that SSRIs such as Celexa, Paxil, Prozac and Zoloft don't always work as expected in every patient.

In fact, "only 30 to 40 percent of people given an SSRI really get a high-quality response" from the drug, Rosenbaum said. "There are a lot of people who are getting a partial or incomplete response or no response at all."

The researchers working with Moffitt also considered the possibility that some people may have a tendency to enter situations where they encounter stressful events and thus get depressed.

But on closer examination, they found that the crises led to new onset of depression among those with the stress-sensitive gene, but those people were not depressed before the crises.

In any given year, 9.5 percent of the U.S. population, or about 18.8 million adults, suffer from a depressive disorder, and most do not seek treatment, according to the National Institute of Mental Health (NIMH). The agency says talk therapy, medications or other methods are effective treatments.

Moffitt says it's too soon to test widely for the presence of the genetic variation. And other experts, while praising the study, agree the results must be replicated.

Although the mouse serotonin study was just the beginning of much more study, Rosenbaum says the finding is "very exciting," because it might someday help us understand "why patients have different sensitivities to various medications, or why they have varying susceptibilities to specific psychiatric conditions."

Rosenbaum said a better understanding of each patient's genetic vulnerabilities might also lead to what's known as psychiatric pharmacogenetics, "where you can screen for the presence or absence of a gene coding for one or the other of these enzymes. If there are differences between people, doctors will be able to predict in advance who'll respond to a serotonin-augmenting drug and who is less likely to do so, so you could spare the person ineffective trials or side effects."

"This is something we've always hoped to do," he said. "Rationally tailor treatment to the individual patient."

On the Web

For more information on depression, see the National Institute of Mental Health Web site.

SOURCES: Terrie Moffitt, Ph.D., professor, Department of Psychiatry, University of Wisconsin, Madison; Jerrold Rosenbaum, M.D., chief of psychiatry, Massachusetts General Hospital, Boston; July 9, 2004, Science
Publication date: February 2008
Authors: Kathleen Doheny and E.J. Mundell, HealthDay Reporters
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