Two gene variations appear frequently in depressed patients who contemplate killing themselves during treatment with a common antidepressant medication, a new study finds.
In the study, reports of suicidal thoughts occurred from 2 to 15 times as often in antidepressant-treated patients with the key gene variations as in patients without them, say psychiatrist Gonzalo Laje of the National Institute of Mental Health in Bethesda, Md., and his colleagues. Participants received citalopram, a widely prescribed antidepressant related to medications such as fluoxetine (Prozac).
"These findings need to be replicated before we can devise a genetic test to determine who's at risk for suicidal thoughts during antidepressant treatment," Laje says.
The study identifies two crucial genes that contribute to the formation of cell receptors for glutamate, a chemical messenger in the brain that has been implicated in antidepressant effects. Variants of these genes apparently promote suicidal thinking only in depressed people taking antidepressants, the researchers conclude in the October American Journal of Psychiatry.
Laje's team studied 1,915 depressed patients recruited from medical facilities across the country for a federally funded trial. Participants received standard doses of citalopram for up to 14 weeks.
The researchers took samples of patients' blood and examined variations in the genetic code at 768 sites on 68 genes that possibly contribute to depression.
Frequencies of various gene versions in the 120 participants who developed suicidal thinking during the trial were compared with DNA patterns in those who did not. Prior studies have estimated that 4 percent of people taking antidepressants start to think about suicide.
Individuals typically inherit two copies of each gene, one from each parent. Some possess two versions of the same gene, while others have a pair of identical genes.
The highest incidence of suicidal thinking occurred in the roughly 1 percent of patients who had inherited at least one variant copy of the first glutamate gene, with or without variant copies of the second glutamate gene. About one-third of these individuals exhibited frequent suicidal thinking.
About 41 percent of participants had one or two variant copies of the second glutamate gene but none of the first. Of these individuals, roughly one-fifth developed thoughts of death and suicide.
A majority of participants—58 percent—had neither high-risk gene version. Fewer than 5 percent of those individuals reported suicidal thinking during treatment.
At a genetics conference next week, Laje's team is to report on two additional gene modifications linked to suicidal thinking in antidepressant-treated patients.
Other researchers who have tracked suicidal thinking among several hundred depressed children and teenagers treated with antidepressants might now try to obtain DNA from those youngsters in order to confirm the new findings, remarks psychiatric epidemiologist Myrna Weissman of Columbia University.
Further research may also yield a genetic test for the likelihood of antidepressant-treatment success, Weissman says. Only 25 percent of patients in Laje's study who developed suicidal thoughts recovered from depression while taking medication, compared with 42 percent of patients who reported no such thoughts.
Genetic Basis of Mood and Anxiety Disorders
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