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Gene Variants Linked to Suicidal Thoughts in Some Men Starting Antidepressant Treatment

Science Update

Some men who experience suicidal thoughts and behaviors after they first start taking antidepressant medications may be genetically predisposed to do so, according to the latest results from the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The results were published in the June 2007 issue of the Archives of General Psychiatry.

Roy Perlis, M.D., of Massachusetts General Hospital, and colleagues analyzed DNA samples of 1,447 STAR*D participants who reported no suicidal thinking or behavior prior to treatment and who received up to 12 weeks of the antidepressant citalopram (Celexa®). Perlis and colleagues focused on the participants' genetic variations—known as single nucleotide polymorphisms (SNPs)—that reside within or nearby the CREB1 gene, which scientists suspect is linked with major depression and possibly related to suicidal thinking and behavior, and also may be involved in how antidepressants work. SNPs are responsible for many of the variations in human genetics, and most scientists believe they may predispose people to certain diseases or influence their response to a medication.

Among the participants, 124 (8.6 percent) developed suicidal thinking after starting treatment, including 54 men. Two of the five SNPs studied were significantly and strongly associated with the onset of suicidal thinking in the men, but not in the women. In previous studies, the same two SNPs appear to be associated with anger among men with major depression—a symptom commonly associated with suicide. Further analyses indicated that none of the five SNPs were linked to suicidal thought and behaviors in men before they began treatment.

The authors conclude that if the results can be replicated, they will have tremendous potential for identifying a subset of people at greater suicidal risk during initial antidepressant treatment.

Perlis R, et al. Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study . Archives of General Psychiatry. 2007 Jun. 64(6):689-697.