Bad blood: chronic inflammation and suicide risk

For some years, it has been established that people who attempt suicide have markers of chronic inflammation in their blood and spinal fluid. Now, an international research collaboration has discovered the enzyme that contributes to this inflammation — and the associated suicidal tendencies.

Researchers from Macquarie University, in collaboration with the Karolinska Institutet in Sweden and the Van Andel Research Institute in the US, analysed certain metabolites — by-products formed during infection and inflammation — in the blood and cerebrospinal fluid from patients who tried to take their own lives. Their study, published in the journal Translational Psychiatry, shows that these patients had reduced activity of an enzyme called ACMSD, which regulates inflammation and its by-products.

“We believe that people who have reduced activity of the enzyme are especially vulnerable to developing depression and suicidal tendencies when they suffer from various infections or inflammation,” said Lena Brundin from the Karolinska Institutet. “We also believe that inflammation is likely to easily become chronic in people with impaired activity of ACMSD.”

Professor Gilles Guillemin, from Macquarie University, explained that ACMSD’s impaired activity results in lower production of picolinic acid, an important molecule for brain protection. The inflammatory product quinolinic acid, meanwhile, is increased. Normally, ACMSD produces picolinic acid at the expense of quinolinic acid, thus maintaining an important balance.

“Commonly used antidepressants have only limited effect because they target serotonin — the branch of tryptophan associated with happiness — rather than quinolinic acid, which is the other branch of tryptophan associated with inflammation,” said Professor Guillemin.

The researchers’ next step is to develop a blood test to detect both quinolinic and picolinic acids to determine individuals who are at risk of taking their lives. The Karolinska Institutet’s Professor Sophie Erhard noted that there are currently “no biomarkers for psychiatric illness”, so a simple blood test would be “a huge step forward”.

Professor Erhard added that the scientists want to find out if reduced ACMSD activity is present not only in individuals with suicidal thoughts, but also those with severe depression. “We also want to develop drugs that might activate the enzyme ACMSD and thus restore the balance between quinolinic and picolinic acid,” she said.