August 01, 2007
Glutamate Receptor Gene Influences Response To Antidepressant

Here's more evidence that cheap DNA testing techniques will make possible drug choices tailored to your personal genetic profile.

A variation in a gene called GRIK4 appears to make people with depression more likely to respond to the medication citalopram (Celexa) than are people without the variation, a study by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, has found. The increased likelihood was small, but when people had both this variation and one in a different gene shown to have a similarly small effect in an earlier study, they were 23 percent more likely to respond to citalopram than were people with neither variation.

The finding addresses a key issue in mental health research: the differences in peopleís responses to antidepressant medications, thought to be based partly on differences in their genes. Some patients respond to the first antidepressant they attempt, but many donít. Each medication takes weeks to exert its full effects, and patientsí depression may worsen while they search for a medication that helps. Genetic studies, such as the one described here, may lead to a better understanding of which treatments are likely to work for each patient.

The ability to avoid the use of drugs that will fail will reduce time until effective treatments are used and therefore, reduce suffering, speed recovery, and reduce costs.

Genetic variations for serotonin and glutamate neuotransmitter receptors influenced how well people responded to citalopram.

In the newest study, researchers examined the genetic material of more of the patients who had participated in STAR*D, for a total of 1,816 samples, and repeated the comparison of DNA from citalopram responders and nonresponders. They discovered that people with the variation in the GRIK4 gene had a higher likelihood of response, and again found that the variation in the HTR2A gene also made people more likely to respond. The results were reproduced, strengthening their validity.

The protein produced by HTR2A acts as a receptor on brain cells for the chemical messenger serotonin, one of several neurotransmitters that enable the cells to communicate with each other. The discovery that a variation in a serotonin-related gene could affect response to citalopram was not entirely surprising, since the serotonin system is known to be involved in depression. Citalopram targets this system.

But GRIK4 makes a protein that acts as a receptor in a different neurotransmitter system, the glutamate system. Recent studies suggest that the glutamate system also is involved in depression, an assertion supported by the new finding.

Genetic testing for drug selection will also help to avoid drugs that will cause patients side effects. For each drug genetic profiles will be found that put one at much higher risk of adverse reactions,. Everyone will have a complete genetic profile that will help guide drug selection for most effect results with least risk of side effects.

Share |      Randall Parker, 2007 August 01 11:15 PM  Brain Genetics


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