Summary: According to a new study, researchers have discovered suicidal patients have reduced activity of an enzyme that regulates inflammation.
Source: Van Andel Research Institute.
It is known that people who have attempted suicide have ongoing inflammation in their blood and spinal fluid. Now, a collaborative study from research teams in the U.S., Sweden and Australia published in Translational Psychiatry shows that suicidal patients have a reduced activity of an enzyme that regulates inflammation and its byproducts.
The study is the result of a longstanding partnership between the research teams of Professor Sophie Erhardt, Karolinska Institutet Professor Lena Brundin at Van Andel Research Institute in Grand Rapids, Michigan, and Professor Gilles Guillemin at Macquarie University in Australia. The overall aim of the research is to find ways to identify suicidal patients.
Biological factors
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, said Erhardt, a Professor at the Department of Physiology and Pharmacology at the Karolinska Institutet, who led the work along with Brundin.
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 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.
Important balance
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.
Funding: The study was funded with the support of the Swedish Research Council, Region Skåne and Central ALF funds. Additional support came from National Institute of Mental Health (NIMH), the American Foundation for Suicide Prevention, Van Andel Research Institute, Rocky Mountain MIRECC, the Merit Review CSR & D and the Joint Institute for Food Safety and Applied Nutrition (University of Maryland), and the Australian Research Council. Several of the researchers have indicated that they have business interests, which are recognized in the article.
Source: Beth Hinshaw Hall – Van Andel Research Institute
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation” by L Brundin, C M Sellgren, C K Lim, J Grit, E Pålsson, M Landén, M Samuelsson, K Lundgren, P Brundin, D Fuchs, T T Postolache, L Traskman-Bendz, G J Guillemin and S Erhardt in Translational Psychiatry. Published online August 2 2016 doi:10.1038/tp.2016.133
[cbtabs][cbtab title=”MLA”]Van Andel Research Institute. “Reduced Activity of Important Enzyme Identified Among Suicidal Patients.” NeuroscienceNews. NeuroscienceNews, 9 August 2016.
<https://neurosciencenews.com/inflammation-suicide-enzyme-4816/>.[/cbtab][cbtab title=”APA”]Van Andel Research Institute. (2016, August 9). Reduced Activity of Important Enzyme Identified Among Suicidal Patients. NeuroscienceNews. Retrieved August 9, 2016 from https://neurosciencenews.com/inflammation-suicide-enzyme-4816/[/cbtab][cbtab title=”Chicago”]Van Andel Research Institute. “Reduced Activity of Important Enzyme Identified Among Suicidal Patients.” https://neurosciencenews.com/inflammation-suicide-enzyme-4816/ (accessed August 9, 2016).[/cbtab][/cbtabs]
Abstract
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
“An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation” by L Brundin, C M Sellgren, C K Lim, J Grit, E Pålsson, M Landén, M Samuelsson, K Lundgren, P Brundin, D Fuchs, T T Postolache, L Traskman-Bendz, G J Guillemin and S Erhardt in Translational Psychiatry. Published online August 2 2016 doi:10.1038/tp.2016.133
