From The Quarterly, Fall 2014

A team that includes three Foundation-funded researchers reported they have identified a biomarker (biological predictor) that, in preliminary tests, predicted suicidal behavior with an accuracy of 80 percent or higher. The potential biomarker can be detected in a simple blood test and appears to predict the progression from thinking about suicide to acting on such thoughts.

Suicide claims the lives of nearly 40,000 Americans annually, representing a rate of the population that has not declined in the last 60 years. In 2011, suicide was the tenth leading cause of death for Americans. These facts motivated Zachary A. Kaminsky, Ph.D., of The Johns Hopkins School of Medicine, a recipient of a 2010 NARSAD Young Investigator Grant, who led a team that also included Holly C. Wilcox, Ph.D. and Jennifer L. Payne, M.D., two prior recipients of Young Investigator grants. Their discoveries were published in The American Journal of Psychiatry on July 30th.

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Brain tissue samples of people who have died by suicide have long been available at a small number of brain tissue banks. In recent years, these precious resources have been studied with increasingly sophisticated genomic tools. Studying these samples, Dr. Kaminsky and colleagues found that the activity level of the SKA2 gene was consistently below normal in cells of the prefrontal cortex (the seat of judgment and impulse control) in those who had died by suicide. The team found that a common variant of the SKA2 gene, in which one DNA “letter” is substituted for another, makes that gene susceptible to an “epigenetic”* chemical change that can lower its activity level. Such changes occur when chemical groups—in this case, a molecule of methyl (CH3)—attach to the gene, preventing it from being expressed.

Dr. Kaminsky is especially interested in epigenetic changes that can promote suicidal pathology. Evidence from the research enabled the team to create a model blood test and try it in two small groups of living people, including people known to be at risk for suicide. The test looks for reduced SKA2 activity, which, the team hypothesizes, is caused by an epigenetic change that prevents brain cells from properly regulating receptors for glucocorticoid stress hormones, most notably cortisol. Abnormal cortisol levels have previously been linked with suicidal behavior.

The hypothesis is that the drop in SKA2 activity in people who die by suicide indicates an inability to properly regulate the response to stress. In people with the telltale SKA2 variation, there is a high risk of suicidal ideation progressing to suicidal action in the presence of a stressor, the team suggests.

According to Dr. Kaminsky and colleagues, “early screening of those at risk for suicidal ideation and suicide attempt may be possible, allowing for the identification of people at risk, proactive treatment, and stress and anxiety reduction.”