Could a blood test screen for suicide risk?

"People with certain gene mutation 'may be more likely to end their life'," reports the Mail Online. A post-mortem study found a gene called SKA2 was less active in the brains of people with mental illness who had committed suicide.

They also found lower activity of this gene in blood samples taken from people who had suicidal thoughts.

However, the study was conducted on a small number of people, and the results could have been caused by other factors. No causal link was shown between the gene activity, suicidal thoughts or actions.

As reported in a similar study last year, there are questions around the usefulness of such a test.

People who are having suicidal thoughts are often secretive about their intent, so it is unlikely they would volunteer for testing.

The management of someone who has suicidal thoughts or severe depression would also not change if they happened to have a negative blood test for this gene.

The test may be useful if used in other ways or in conjunction with other tests, however.

Where did the story come from?

The study was carried out by researchers from Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health.

It was funded by a National Institute for Mental Health grant, the Johns Hopkins Center for Mental Health Initiatives, the Solomon R and Rebecca D Baker Foundation, and the James Wah Award for Mood Disorders. 

There is a potential conflict of interest, as two of the authors are listed as co-inventors on a patent to evaluate risk of suicidal behaviour using genetic and epigenetic variation at the SKA2 location.

The study was published in the peer-reviewed medical journal, the American Journal of Psychiatry.

The Mail Online generally overstated the ability of this test to accurately predict who is at risk of suicide and its practical usefulness in real-world situations.

What kind of research was this?

This was a combination of a post-mortem study, a cross-sectional study and cohort studies.

The authors report the annual suicide rate in the US has been relatively stable over the last 60 years at 10 to 12 suicides per 100,000 people.

As part of efforts to reduce this rate by 20% over five years, the researchers wanted to find a way to identify and target people at greatest risk.

They aimed to identify associations in gene expression in the brain tissue of people who had committed suicide compared with those who had not. They then wanted to assess whether these would be present in blood samples and if the levels were raised in times of stress and anxiety.

The researchers also measured the levels of the hormone cortisol in a small group of participants and looked at whether this had an association with suicidal thoughts and the level of gene expression.

Cortisol is essential for life and regulates the response to all types of stress, including illness, physical exertion and emotional stress.

Cortisol levels vary over the day and are highest on waking and lowest before sleep, and increase in response to stress.

What did the research involve?

The researchers performed a genome-wide screen for DNA methylation in samples of brain tissue from 98 people who had committed suicide compared with 70 people who had died from other causes. All 98 people either had major depression, bipolar disorder or schizophrenia.

DNA methylation is one of the ways a cell can dampen down the expression of a certain region of DNA. Where methylation occurs, it physically blocks the mechanism by which DNA is read. This disrupts gene activity, but not to the extent that we would say a genetic mutation had occurred, as the actual structure of the gene is unchanged. 

The level of expression of the identified gene was then measured in blood samples from people who were enrolled in three other studies:

• 22 samples from the Genetics of Recurrent Early-Onset Depression (GenRED) offspring study – adolescents and adults who had a parent with a mental illness
• 325 samples from the Prevention Research Center study
• 51 samples from a cohort of pregnant women who had previously suffered from major depression or bipolar disorder

The researchers compared the blood results from people who had suicidal thoughts at any point in their life with those who had not (according to questionnaires or interviews).

They also took cortisol blood samples from the GenRED group and looked at the level of gene expression and the level of anxiety during the test. These were taken on waking, 30 minutes later and then 60 minutes after waking.

They adjusted the results to account for age, sex, race and length of time between death and post-mortem.

What were the basic results?

A gene called SKA2, which codes for a protein necessary for cell division, was found to be less active in the brain samples of people who had committed suicide compared with people who had not. The DNA methylation, which reduces the gene activity, was correspondingly higher.

The level of DNA methylation of SKA2 was higher in the blood samples of people who had suicidal thoughts compared with those who did not.

Waking cortisol levels were higher in people who reported suicidal thoughts, but there was no association 30 and 60 minutes after waking.

How did the researchers interpret the results?

The researchers concluded their findings "implicate SKA2 as a novel genetic and epigenetic target involved in the aetiology of suicide and suicidal behaviours".

They say that, "Early screening of those at risk for suicidal ideation and suicide attempt may be possible, allowing for the identification of individuals at risk, proactive treatment, and stress and anxiety reduction."

Conclusion

This study has shown an association between reduced levels of activity of the SKA2 gene and suicide. However, no causal link was shown between the gene activity, suicidal thoughts or actions.

There are questions around the usefulness of such a test becoming commonly used. Presumably screening would be voluntary, so people considering suicide may simply not turn up for screening.

And the management of someone who has suicidal thoughts would arguably not change if they happened to have a negative blood test for this gene. If someone had severe depression, you couldn't discount a potential suicide risk.

There were also several limitations of this study, which include:

• All the people who committed suicide had a diagnosed mental illness. This or other confounding factors could have accounted for the difference seen in SKA2.
• There was no standardised measure of the presence of suicidal ideation (thinking about committing suicide) across the three groups of living participants.
• People were considered to have suicidal ideation regardless of when the thoughts occurred, and the severity or frequency of the thoughts was not measured.
• The measurement of cortisol and links with suicidal ideation and SKA2 was only conducted on 22 people, which is a very small sample size. It may not be representative of larger groups.
• The study claimed a blood test for the DNA methylation markers could predict future suicidal ideation and suicide attempt with more than 80% accuracy. However, the authors acknowledged these results were based on very few people, so may not be reliable.

If you have suicidal thoughts, help is available through your GP or helplines such as the Samaritans, who can be reached 24 hours a day, 365 days a year on 08457 90 90 90.