Specific variations in two genes have been linked to suicidal thoughts in patients taking a selective serotonin reuptake inhibitor, according to an article in the October issue of the American Journal of Psychiatry.

The large-scale study was led by scientists at the National Institutes of Health's National Institute of Mental Health. Depending on the particular genotype, the variations increased the likelihood of such thoughts from 2- to15-fold. About 1 percent of adult patients were deemed to be at high genetic risk, 41 percent at elevated risk, and 58 percent at lower risk.

If confirmed, the findings may hold promise for genetic testing prior to beginning antidepressant therapy as more such markers are identified.

Risk increased proportionately if a participant were homozygous for a variation rather than heterozygous. Both genes code for components of the brain's glutamate system, which recent studies suggest is involved in response to antidepressants.

Overall, about 6 percent of 1,915 patients with depression reported that they started to have suicidal thoughts while taking an antidepressant. This rate soared to 36 percent among the few patients who were homozygous for a variation; 59 percent of patients who had suicidal thoughts had at least one of the variants.

Francis J. McMahon, MD, Gonzalo Laje, MD, The Institute’s Mood and Anxiety Disorders Program, and colleagues at the National Human Genome Research Institute, Mount Sinai School of Medicine, and the University of Texas Southwestern Medical Center, were involved in the research.

"These data suggest that genetics may soon help us in our quest to individualize treatments for depression," said Institute Director Thomas R. Insel, MD.

"In the future, we hope that genetic testing will help doctors identify those few patients who are at high risk for suicidal thinking during antidepressant therapy and need close monitoring or alternative treatments," said McMahon. "This should help allay concerns for the vast majority of patients. The best way to prevent suicide is to treat depression."

McMahon and colleagues hope that the newly identified versions may prove useful in identifying patients who need closer monitoring, alternative treatments and/or specialty care - while reassuring those for whom selective serotonin reuptake inhibitors are appropriate.