ACMSD Enzyme Has Reduced Activity In Suicidal Patients

It has been established that individuals who have attempted suicide have ongoing inflammation in their blood and spinal fluid. Now, a collaborative study from research teams in Sweden, the US and Australia shows that suicidal patients have a reduced activity of ACMSD, an enzyme that regulates inflammation and its byproducts.

Sophie Erhardt, a Professor at the Department of Physiology and Pharmacology at the Karolinska Institutet, who led the work along with Lena Brundin, said:

“Currently, there are no biomarkers for psychiatric illness, namely biological factors that can be measured and provide information about the patient’s psychiatric health. If a simple blood test can identify individuals at risk of taking their lives, that would be a huge step forward.”

The study is the result of a longstanding partnership between the research teams of Professor Erhardt, Professor Brundin at Van Andel Research Institute, and Professor Gilles Guillemin at Macquarie University in Australia. The general aim of the research is to find ways to identify suicidal patients.

Reduced ACMSD And Inflammation

The researchers analyzed certain metabolites, byproducts formed during infection and inflammation, in the blood and cerebrospinal fluid from patients who tried to take their own lives. Previously it has been shown that such patients have ongoing inflammation in the blood and cerebrospinal fluid.

This new work has succeeded in showing that patients who have attempted suicide have reduced activity of an enzyme called amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD), which regulates inflammation and its byproducts.

“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. We also believe that inflammation is likely to easily become chronic in people with impaired activity of ACMSD,” said Brundin

Balance Important

The substance that the enzyme ACMSD produces, picolinic acid, is greatly reduced in both plasma and in the spinal fluid of suicidal patients.

Another product, called quinolinic acid, is increased. Quinolinic acid is inflammatory and binds to and activates glutamate receptors in the brain. Normally, ACMSD produces picolinic acid at the expense of quinolinic acid, thus maintaining an important balance.

“We now want to find out if these changes are only seen in individuals with suicidal thoughts or if patients with severe depression also exhibit this. We also want to develop drugs that might activate the enzyme ACMSD and thus restore the balance between quinolinic and picolinic acid,” Erhardt said.

L Brundin, et al
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
Translational Psychiatry (2016) 6, e865; doi:10.1038/tp.2016.133

Image: Tom Ellenberger, Washington University School of Medicine in St. Louis, and Dave Gohara, Saint Louis University School of Medicine