https://www.newscientist.com/article...-gene-changes/Suicidal behaviour predicted by blood test showing gene changes
Variations in gene activity seem to indicate when someone is considering suicide. A test for it could save lives - and shake up psychiatry
CAN you spot whether someone is likely to try to take their own life? In hindsight, it can seem obvious, but at the time, doctors and relatives rarely have much more than intuition to go on. Now a blood test could help doctors identify those most at risk. The idea marks a shift in diagnostic approaches to mental health, and has drawn criticism from some psychiatrists.
Nearly a million people worldwide take their own lives each year. Prevention efforts have done little to curb suicide rates in most countries, in part because it is often so difficult to tell if someone is planning to do it.
Chemicals in the blood may provide a much-needed clue. Alexander Niculescu of Indiana University in Indianapolis and his colleagues have developed a questionnaire and blood test that together predicted with 92 per cent accuracy who among a group of 108 men receiving psychiatric treatment would develop suicidal feelings over the next year (Molecular Psychiatry, doi.org/6vk). Preliminary evidence suggests the test also works for women.
Because only about 16 in every 100,000 people end their own lives, a test with such a level of accuracy will give many false positive and false negative results if used on the general population. But it could prove useful for people who are already having psychiatric care, especially those who are addicted to drugs, incarcerated or have a family history of suicide, all of which are known suicide risk factors.
Although many factors like these are identified after a person kills themself, none are predictive. While 90 per cent of people who kill themselves have been diagnosed with depression, only 2 per cent of people with depression kill themselves.
"Those who are serious about taking their own lives are often the least likely to reveal it and seek help," says Gustavo Turecki at McGill University in Montreal, Canada.
"Those who are serious about taking their own lives are least likely to reveal it or seek help"
A test that can spot suicidal intentions without relying on self-disclosure would help doctors to start preventative measures, such as putting someone on suicide watch. This typically involves preventing someone from leaving hospital, confiscating potentially hazardous items and continually monitoring behaviour. Research shows that suicide attempters can be dissuaded from trying again, so the test might tell who could benefit from receiving such intervention before they have even tried to take their life.
To develop the test, over several years Niculescu's team took blood samples from 217 men undergoing various psychiatric treatments. They compared changes in gene expression in 37 of them who developed suicidal feelings with previously published work and with post-mortem samples of 26 men who had killed themselves. They identified 11 gene changes that could be biological markers for spotting people who might be considering suicide (see "Changing of the genes"), and they monitored these same markers in a test group of 265 men with psychiatric conditions.
They combined the blood test data with an app that asks questions designed to detect suicidal intentions, and predicted with 92 per cent accuracy who of a group of 108 men receiving psychiatric treatment would develop suicidal feelings over the following year - and with 71 per cent accuracy who of a group of 157 would be hospitalised by an attempt.
"They were able to guess the future for hundreds of people," says Zachary Kaminsky of Johns Hopkins University in Baltimore, Maryland. "This is top-notch."
Linking biomarkers to mental health is a controversial topic. Since 2010, the US National Institute of Mental Health (NIMH) has been increasingly funding studies like these, which look for biological markers or changes in the body when someone shows certain psychiatric symptoms, regardless of what their psychiatric diagnosis might be.
"When someone comes to hospital with an injury or an overdose, it can be hard to tell if it was on purpose"
This marks a move away from studies that use the diagnostic categories defined by the Diagnostic and Statistical Manual of Mental Disorders, such as depression, bipolar disorder or schizophrenia, a system that has been criticised for relying on the subjective assessments of doctors rather than clinical tests.
While mortality linked to physiological conditions like cardiac disease has fallen, suicide rates are at an all-time high across all age groups in the US. In the UK, rates have been rising steadily since 2007, and similar trends are seen in other countries. The desire to have psychiatry benefit from biological advances in the same way as the rest of medicine is why the NIMH has changed its approach. But the shift towards detecting biomarkers by neuroimaging or monitoring gene expression has drawn criticism.
"The NIMH is funding biomarker po*n," says James Coyne of University Medical Center in Groningen, the Netherlands. "It's airbrushed, heavily edited, and you can't replicate it at home."
Coyne's view is shaped by the small sample sizes used in early mental health biomarker research - something that can be problematic for rare conditions.
"It is extremely unlikely that a few genes are going to be able to predict risk for suicidality. It certainly won't in all cases," says Emil Coccaro of the University of Chicago. He is concerned that when biomarkers are used, other factors are ignored, such as what is happening in a person's life. Biomarkers may help you understand risk factors, but predicting subsequent behaviour is more difficult, says Turecki.
Hospital help
Niculescu's test has already proved successful where it would be used most - in hospitals. There, people are at a higher risk of suicide than the general population. Niculescu and his team found the test was especially predictive for people with bipolar disorder, predicting with 98 per cent accuracy which of them would develop suicidal thoughts, and with 94 per cent accuracy who would make an attempt serious enough to require hospitalisation. "It could be used as a screening instrument," says Niculescu. "If somebody scored highly, they could be followed more closely, be hospitalised longer, their medications added or changed."
"It's really a groundbreaking study," says Bruce Cuthbert, who oversees the NIMH's push for biology-based diagnostics. He thinks a combination of an app and a blood test could be useful in emergency room settings - for example, to help determine whether an incident was likely to have been a suicide attempt. "Sometimes someone appears following an injury or an overdose," says Cuthbert. "Was it an accident or did they do it on purpose?" Emergency doctors often have very little to go on in making such a judgement.
Niculescu wants to extend his tests to the general public, but Kaminsky says the low rate of suicide in the general population would mean too many false alarms.
Regardless of whether these tests are used, the discovery of biomarkers is important for people who are suicidal but are dismissed by others as being lazy or lacking discipline, says Cuthbert. "It validates their sense that they have a real illness."
Changing of the genesThe activity of 11 genes seems to change when someone is thinking about committing suicide, according to work by Alexander Niculescu of Indiana University in Indianapolis and his colleagues (see main story).
Knowing the function of these genes could help us understand the biology behind this behaviour.
One of the genes is called SKA2, which indirectly affects the workings of the hypothalamic-pituitary-adrenal axis, a network of brain systems that is implicated in impulsive and negative thoughts. When this gene's activity is turned down, the HPA axis becomes hyperactive, leading to runaway thoughts. Overactivity of this brain area has been repeatedly linked to suicide attempts.
Another of the genes, SLC4A4, is involved in regulating the pH of the brain, which has been linked to anxiety and panic attacks. It could be that in some cases, strong suicidal thoughts are similar to impulsive panic attacks, says Niculescu.
This article appeared in print under the headline "Suicide in the blood"
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