Suicidal Thoughts
Suicide is the 10th leading cause of death worldwide

Scientists have found an enzyme related to brain inflammation which appears to predict the risk of suicidal behaviour. This discovery could pave the way to better identify vulnerable people and prevent them from attempting suicide.

In the UK, the suicide rate stands at about 10.8 deaths per 100,000 population. The World Health Organisation estimates that around the world, more than 800,000 suicides occur every year, making it the 10<sup>th leading cause of death globally.

While prevention strategies and close monitoring of people with risk factors – such as developing a severe mental health disorder – can reduce the number of deaths, scientists still struggle to understand whether there are biological and genetic mechanisms that drive suicidal behaviours.

Clinical data accumulated over the past decades suggest that the immune system of people who are depressed, or who engage in suicidal behaviours, responds to stress with inflammation. However, this phenomenon remains poorly understood.

The new study, published in the journal Translational Psychiatry, investigated the role of an enzyme known as ACMSD – suggesting that people with a decreased activity of this specific enzyme may be more at risk of suicide.

High acid levels

The scientists, from the Van Andel Research Institute (US), worked with 137 patients exhibiting suicidal behaviour and 71 healthy controls, collecting blood and cerebrospinal fluid samples. They examined these samples to estimate the levels of two acids: the picolinic acid and the quinolinic acid.

Previous studies have shown that these acids play a key role in inflammation. Quinolinic acids are produced in excessive levels when an inflammation occurs while levels of picolinic acid – known to have neuroprotective effects – are too low.

This exact pattern of acid levels was observed in participants who had attempted suicide, confirming the link between inflammation and suicidal behaviour. Indeed, in the samples analysed, quinolinic acid levels were abnormally high and picolinic acid levels were low – both directly after a suicidal attempt, but also at various points over the next two years.

ACMSD enzyme and suicide prevention

These two acids are regulated by the enzyme ACMSD, so the researchers conducted genetic analysis to show whether genes could be blamed for a defective ACMSD activity in participants with suicidal behaviours.

They discovered that individuals who had attempted suicide were more likely to possess a specific variant of the gene coding for ACMSD, associated with increased levels of quinolinic acid.

It is important to note, however, that the study merely highlights a correlation between ACMSD and suicide. It does not say that having lower activity of ACMSD necessarily causes suicide. Many other environmental factors may come into play.

The two acids examined in this study could in the future be investigated as bio-markers of suicide. On the long term and with further, larger studies, the creation of a blood test to identify acid levels in people and predict their risk of suicide may become possible.

Additionally, this study doesn't show if increasing ACSMD activity and restoring the picolinic-quinolinic ratio would prevent suicidal behaviour, so this is an area that will also have to be researched further in recent years.