Finding could lead to new treatments for depression

SAN ANTONIO (Dec. 3, 2008) — A discovery by researchers at The University of Texas Health Science Center at San Antonio could lead to new treatments for millions of depression sufferers who do not respond well to the most commonly prescribed antidepressants.

Researchers identified a potential new target for treatment and found evidence that it might play a large role in cases where existing antidepressants are most ineffective. The research appeared in the Dec. 2 print edition of Proceedings of the National Academy of Sciences of the United States of America.

The exact cause of depression is not known, but it has long been thought to be related to low levels of the neurotransmitter serotonin in the gaps between nerve cells. Many popular antidepressants – called selective serotonin reuptake inhibitors (SSRIs) – prevent nerve cells from taking in serotonin, causing serotonin levels to increase outside the cell. Familiar brand names like Prozac, Paxil and Zoloft are SSRIs.

Nerve cells have a number of “serotonin transporters,” which act as gateways that can usher serotonin inside cells or shut it out. SSRIs effectively block those gateways, causing serotonin to build up outside the cell, where it seems to have a therapeutic effect.

The Health Science Center research focused on a genetic variation so common that it is found in more than half of the human population. People with this variation have fewer serotonin transporters, which logically would mean fewer ways for serotonin to get inside the cell and therefore more serotonin outside the cell.

Conventional wisdom suggests that this might offer some protection from depression. But that is not the case. “These people are not only more likely to suffer depressive episodes, but they’re actually quite resistant to treatment with SSRIs,” said Lynette C. Daws, Ph.D., the study’s principal investigator and an associate professor in the Health Science Center’s Department of Physiology.

Knowing how adaptable the brain is, researchers speculated that something else was compensating for the genetic loss of serotonin transporters. What they found were organic cation transporters (OCTs), which serve as alternate routes into nerve cells. The study found that these OCTs work harder in mice with fewer serotonin transporters.

“So if these aren’t blocked as well, they’re more or less undoing any good that blocking the serotonin transporters would do,” Dr. Daws said.

Perhaps the most significant finding is that a drug that blocks OCTs – the same way that SSRIs shut down serotonin transporters – has an antidepressant effect in mice.

This knowledge could be used to develop antidepressant medications that are more effective for people who do not respond to SSRIs. And it’s possible that pairing an SSRI with an OCT blocker could improve treatment even for those who do not have the genetic variation.

The next series of experiments will look at chronic use of OCT blockers. “If it were going to be effective in humans, we have to show that the animals don’t become tolerant to it,” Dr. Daws said. Researchers also plan to study how OCT blockers affect adolescents, who are particularly difficult to treat for depression.

Note to media: Dr. Daws will be traveling for a few days but is reachable through External Affairs. She will return Friday, Dec. 12.

 

 

 

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $16.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 24,000 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.



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