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Finding may eventually help tailor treatment for depression

November 08, 2007

When a treatment works for one person's depression, it does not always work for another person's. Findings from the University of Iowa may one day help doctors have a better idea of who will benefit from specific antidepressants, increasing the likelihood of successful treatment.

The study focused on a gene associated with the availability of serotonin, a chemical that at low levels can affect mood and sleep. The researchers found that among people with a variation in this gene, women were more likely than men to have altered processes related to serotonin.

The results, which were based on genetic analysis and depression assessments for 192 individuals, appeared online Nov. 7 in the American Journal of Medical Genetics.

While the finding is exciting, the researchers caution that they have not found a "depression gene," as genes alone cannot cause behaviors.

"Genes, in conjunction with a person's exposure to different life experiences and environments, play a role in depression, even though all the specific mechanisms by which this happens are not well understood," said the study's lead author, Robert Philibert, M.D., Ph.D., associate professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine. "This study gave us some interesting information about one specific mechanism."

The study participants -- 96 men and 96 women -- have been ongoing participants for more than 20 years in the Iowa Adoption Studies, initiated by Remi Cadoret, M.D., a UI professor of psychiatry who died in 2005.

The UI team investigated the function of SLC6A4, a serotonin transporter gene. They found that methylation of the gene -- a process that turns off a gene's functions -- occurred more often in women with the variant than men with the variant. This means that in some women less gene expression resulted in less mRNA, which is the genetic material that helps a gene make a protein.

Tracy Gunter, M.D., UI assistant professor of psychiatry and a study co-author, said, "It's important to keep in mind that genes by themselves don't code for behavior. They code for proteins, and the way you get from a gene to a protein is through messenger RNA or mRNA. Methylation, however, prevents production of mRNA."

Philibert and colleagues are investigating the data to see if they can find out what actually relates to the methylation changes.

The team also assessed the participants for depression, but could not directly correlate cases of depression with those who have the gene variant.

"The gene variant we studied may make some people more prone to develop depression if they experience more stress or abuse -- similar to how, if two people have a genetic risk for osteoporosis, the one who runs may be more likely than the one who swims to actually develop osteoporosis," Philibert said.

Currently, depression is often treated with Selective Serotonin Reuptake Inhibitors (SSRIs) that help make serotonin available for processes that ultimately help manage mood and stress.

Gunter said that the UI study, combined with other studies, creates a clearer picture about serotonin and depression, at least in some people.

"For the past 10 years or so, some other groups' findings have suggested that women respond better than men to SSRIs. In late 2006, a study indicated that women in their pre-menopausal years may get better more frequently than men on SSRIs," she said.

"So when you look at our results in light of such a study, you're starting to put together a picture that probably describes the truth of the matter for at least a percentage of women with depression. Down the road, if we can find the people for whom this is a problem, we can target specific interventions for them. In other words, we can guess right the first time," Gunter added.

University of Iowa