NeuroMark reports that it will soon release Mark-C™, a genetic test to identify people at risk of suicidal ideation when prescribed citalopram. The test includes the genetic markers found by a study led by scientists at NIMH and additional markers chosen to increase the predictive power of the test. Mark-C is designed to predict people at high and low risk of suicidal ideation when on the drug.
The NIMH-led group linked specific variations in two genes to suicidal thinking in patients on citalopram. Depending on the particular mix inherited, they explain, the likelihood of such thoughts increased from 2- to 15-fold.
The scientists screened genetic material from 1,915 adult participants with major depression in level one of the NIMH-funded STAR*D (Sequenced Treatment Alternatives for Depression) trial. They were treated with the selective serotonin reuptake inhibitor (SSRI) citalopram. The researchers then looked for associations between self reports of suicidal thinking and over 700 sites in 68 suspect genes.
The investigators found that certain versions of two genes that code for glutamate receptors were more prevalent in patients with suicidal thinking.
They report that 1% of the participants had a version of the kainate receptor gene, GRIK2, that boosted the odds for suicidal thinking more than eightfold. Also, 41% had a version of the AMPA receptor gene, GRIA3, that raised the chances of suicidal thinking nearly twofold. About 0.5%, or 11 participants, had both high-risk gene versions, resulting in a 15-fold increase. Of these volunteers, four developed suicidal thinking.
Neither version was related to self-reported history of suicide attempts, suggesting that the versions are specific to suicidal thoughts that occur during antidepressant treatment, the scientists explain.
The investigators point out, however, that more than 40% of those who developed suicidal thoughts lacked one of the these two versions. They will report on identification of additional versions that emerged from a scan of the whole genome in STAR*D patients at a genetics conference in October.
The NIMH study was performed in collaboration with colleagues at the National Human Genome Research Institute, Mount Sinai School of Medicine, and the University of Texas Southwestern Medical Center University of Texas Southwestern Medical Center. It will be reported in the October ssue of The American Journal of Psychiatry.