Chemical Alteration

07.30.14

Researchers Have Created a New Blood Test to Predict Risk of Suicide

In a groundbreaking new genetic discovery, doctors from Johns Hopkins have found a mutation involved in how the brain reacts to stress that can reliably predict suicide risk.

With suicide, there’s often talk of “warning signs.” But a new genetic discovery could be the key to creating a blood test that could, for the first time, use DNA to determine a person’s risk of suicide.

The research, published in The American Journal of Psychiatry, comes from a group of Johns Hopkins University doctors who in a series of experiments—three with brains, three with blood—found that a mutation in a specific gene involved in how the brain reacts to stress, SKA2, could predict reliably whether a person is at risk of attempting suicide.

“We’ve identified a new player in suicide,” Dr. Zachary Kaminsky, lead author and assistant professor of psychiatry and behavioral sciences at Johns Hopkins, told The Daily Beast.

This study follows previous research in which Kaminsky and his colleagues identified a chemical alteration that can identify women at risk of postpartum depression. Suicide, like postpartum depression, is associated with an underlying hormonal cause—estrogen for new mothers and the stress hormone cortisol in suicide.

“If we can identify who is at risk, we may be able to intervene in effective ways. Notably, we could identify individuals in military populations who are more vulnerable to stress.”

“We get stressed out and flooded with cortisol,” Kaminsky explains. “We have to wake up, fight or flight, run away, or just catch a cab to work. Cortisol is going to go up, but it should go back down again. We think SKA2 is important in that. If you have less, which is what we’re finding, then you’re going to have less of an ability to turn that off.”

The researchers first noticed the SKA2 mutation during a larger genome scan of postmortem brain samples from both healthy people and those with mental illness. Brains from people who had died by suicide had less of the SKA2 gene. Further, the researchers found evidence of an epigenetic modification, or a chemical change not in the DNA itself but the way it functions in the body.

Epigenetics—literally “on top” of the DNA—is the science dealing with the instructions that bind to genes and control genetic expression, or in this case, suppression. Although the gene itself stays unchanged, chemicals called methyl groups alter how that gene works. Higher levels of methylation were found in those who had committed suicide. These methyl groups act like light switches turning genes on and off, dimmer and brighter, and can be affected by environmental factors such as pollution, nutrition, and stress.

Armed with the new information, Kaminsky and his team tested blood samples from living people and again found methylation increases, or “bad instructions,” in those with reported thoughts of suicide or attempts.

The researchers then used the findings to create a model analysis through which they ran all the previous samples and found they were able to predict those at risk of suicide with 80 percent to 90 percent accuracy based on the severity of the risk.

Although previous studies have attempted to identify the biomarkers of suicide that would make such a blood test possible, this is the first to do so with such accuracy. And while Kaminsky is cautious, noting in particular the limitations of a small sample size—about 550—he appears optimistic about the possible implications.

“If we can identify who is at risk, we may be able to intervene in effective ways,” Kaminsky said. “Notably, we could identify individuals in military populations who are more vulnerable to stress. We know they’re going to be experiencing stress when they go off to combat.”

To that effect, the next step of the research involves a testing hundreds more samples from soldiers pre- and post-deployment as part of a collaboration with the U.S. Army STARRS project, the nation’s largest-ever study of mental health in the military.

It can’t come fast enough. Overall, suicide is the 10th-leading cause of death in the United States, according to the Centers for Disease Control and Prevention. And at 18.7 per 100,000, the rate for active service members is more than 50 percent higher than the national suicide rate, which has hovered near 12 per 100,000 for the last 60 years. A recent analysis by the investigative journalism group News21 found the suicide rate for veterans is twice that of civilians.