Genetic Blood Test Could Predict Suicide Risk

A chemical alteration in a single human gene linked to stress reactions could give doctors a simple blood test to reliably predict a person’s risk of attempting suicide.

The discovery 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.

Scientists at the Johns Hopkins University School of Medicine (Baltimore, MD, USA) obtained postmortem prefrontal cortical tissue samples from a tissue bank and blood samples from different cohorts. The team tested three different sets of blood samples, the largest one involving 325 participants in the Johns Hopkins Center for Prevention Research. A discovery set of prefrontal cortical tissue data was created from 10 Caucasian individuals with major depression for whom bulk tissue data were available; seven died by suicide, and three did not. A replication set consisted of the remaining eight suicide and four non-suicide samples from Caucasians with major depression.

Genome-wide DNA methylation data were obtained from Illumina HM450 microarrays (Illumina; San Diego, CA, USA; www.illumina.com). Pyrosequencing was conducted in microarray-identified loci in all individuals. All gene expression data and genotyping was performed by using quantitative real-time polymerase chain reaction (PCR) on an ABI 7900HT Fast Real-Time PCR system (Life Technologies; Grand Island, NY, USA). The team focused on a genetic mutation in a gene known as Spindle and Kinetochore Associated Complex Subunit 2 (SKA2). By looking at brain samples from mentally ill and healthy people, the scientists found that in samples from people who had died by suicide, levels of SKA2 were significantly reduced.

Some subjects had an epigenetic modification that altered the way the SKA2 gene functioned without changing the gene's underlying DNA sequence. The modification added chemicals called methyl groups to the gene. Higher levels of methylation were then 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.

Zachary Kaminsky, PhD, the study leader, said, “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. 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.” The test might best be used to predict future suicide attempts in those who are ill, to restrict lethal means or methods among those a risk, or to make decisions regarding the intensity of intervention approaches. The study was published on July 30, 2014, in the American Journal of Psychiatry.

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