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Aug 1, 2007

Second Gene Variation Found that Improves Response to Antidepressant

  • National Institute of Mental Health (NIMH) scientists found a variation in the gene GRIK4 that appears to make people with depression more likely to respond to Forest Laboratories’ Celexa than people without the variation. This increase 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% more likely to respond to Celexa than were people with neither variation.

    The researchers studied DNA provided by patients participating in a recently completed NIMH clinical trial, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The trial showed that depressed patients who don’t benefit from the first medication they try, in this case Celexa, have a fair chance of being helped by others.

    After the study, investigators evaluated the DNA codes contained in 68 genes suspected of being involved in depression, collected from 1,297 of the patients who had participated in STAR*D. In a study published in May 2006, researchers compared the DNA codes of those who had responded to Celexa and those who hadn’t; the scientists found that responders were more likely to have a variation in the gene HTR2A. The protein produced by HTR2A acts as a receptor on brain cells for the chemical messenger serotonin.

    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 Celexa responders and nonresponders. They discovered that people with the variation in the GRIK4 gene, which makes a receptor protein in the glutamate system, had a higher likelihood of response and again found that the variation in the HTR2A gene also made people more likely to respond.

    Scientists from the National Human Genome Research Institute, the National Institute on Alcohol Abuse and Alcoholism, Mount Sinai School of Medicine, and University of Texas Southwestern Medical Center also contributed to the research.

    Results of the study are in the August issue of the American Journal of Psychiatry.



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