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A Blood Test for Suicide?

Researchers look for gene mutation

Johns Hopkins researchers say they have discovered a chemical alteration in a single human gene linked to stress reactions that, if confirmed in larger studies, could give doctors a simple blood test to reliably predict a person’s risk of attempting suicide.

The discovery, described online in the American Journal of Psychiatry, suggests that changes in a gene involved in the function of the brain’s response to stress hormones plays a significant role in turning what might otherwise be an unremarkable reaction to the strain of everyday life into suicidal thoughts and behaviors.

“Suicide is a major preventable public health problem, but we have been stymied in our prevention efforts because we have no consistent way to predict those who are at increased risk of killing themselves,” said leader investigator Zachary Kaminsky, PhD. “With a test like ours, we may be able to stem suicide rates by identifying those people and intervening early enough to head off a catastrophe.”

For their experiments, Kaminsky and his colleagues focused on a mutation in a protein-coding gene known as SKA2, which is expressed in the prefrontal cortex of the brain. SKA2 proteins are involved in inhibiting negative thoughts and in controlling impulsive behavior. Specifically, they are responsible for chaperoning stress hormone receptors into cells’ nuclei so that they can do their job. If there aren’t enough SKA2 proteins, or if they are altered in some way, stress hormone receptors are unable to suppress the release of cortisol throughout the brain. Previous research has shown that such cortisol release is abnormal in people who attempt or die by suicide.

By looking at brain samples from mentally ill and healthy people, the researchers found that levels of the SKA2 protein were significantly reduced in samples from people who had died by suicide.

The investigators also found an epigenetic modification that altered the way the SKA2 gene functioned without changing the gene’s underlying DNA sequence. This modification added chemicals called methyl groups to the gene. Higher levels of methylation were found in the same study subjects who had killed themselves. The higher levels of methylation among suicide decedents were then replicated in two independent brain cohorts.

In blood samples from 325 participants, the researchers found similar methylation increases at SKA2 in individuals with suicidal thoughts or attempts. They then designed a model analysis that predicted with 80% certainty which of the participants were experiencing suicidal thoughts or had attempted suicide. Those with a more severe risk of suicide were predicted with 90% accuracy. In the youngest data set, the researchers were able to identify with 96% accuracy whether a subject had attempted suicide, based on blood test results.

Kaminsky said that a test based on these findings might best be used to predict future suicide attempts in those who are ill, to restrict lethal means or methods among those at risk, or to make decisions regarding the intensity of intervention approaches. The test might also be useful in a psychiatric emergency room, he says, as part of a suicide risk assessment.

“We have found a gene that we think could be really important for consistently identifying a range of behaviors from suicidal thoughts to attempts to completions,” Kaminsky said. “We need to study this in a larger sample, but we believe that we might be able to monitor the blood to identify those at risk of suicide.”

Source: Johns Hopkins; July 30, 2014.

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