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An enzyme in the ky...
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
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- Brundin, L. (author)
- Van Andel Research Institute, MI 49503 USA
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- Sellgren, C. M. (author)
- Karolinska Institutet,Karolinska Institute,Karolinska Institute, Sweden; Broad Institute MIT and Harvard, MA USA; Massachusetts Gen Hospital, MA USA,Massachusetts General Hospital
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- Lim, C. K. (author)
- Macquarie University, Sydney,Macquarie University, Australia
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- Grit, J. (author)
- Van Andel Research Institute, MI 49503 USA,NHMRC Centre of Research Excellence in Suicide Prevention,Macquarie University, Australia; NHMRC Centre Research Excellence Suicide Prevent CRESP, Australia
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- Pålsson, Erik, 1975 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Gothenburg University, Sweden
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- Landén, Mikael, 1966 (author)
- Karolinska Institutet,University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Gothenburg University, Sweden
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- Samuelsson, Martin (author)
- Linköpings universitet,Linköping University,Karolinska Institute,Avdelningen för neuro- och inflammationsvetenskap,Hälsouniversitetet,Region Östergötland, Psykiatriska kliniken,Karolinska Institute, Sweden
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- Lundgren, Kristoffer (author)
- Linköpings universitet,Linköping University,Institutionen för medicin och hälsa,Hälsouniversitetet
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- Brundin, P. (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Van Andel Research Institute, MI 49503 USA
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- Fuchs, D. (author)
- Medical University of Innsbruck, Austria
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- Postolache, T. T. (author)
- Rocky Mountain MIRECC for Veteran Suicide Prevention,University of Maryland, MD 21201 USA; Rocky Mt MIRECC, CO USA
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- Träskman Bendz, Lil (author)
- Lund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden
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Guillemin, G. J. (author)
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- Erhardt, S. (author)
- Karolinska Institutet,Karolinska Institute,Karolinska Institute, Sweden
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(creator_code:org_t)
- 2016-08-02
- 2016
- English.
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Abstract
Subject headings
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- 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-beta-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-Asberg 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- major depressive disorder
- epsilon-semialdehyde decarboxylase
- high-protein diet
- quinolinic acid
- picolinic-acid
- chromium picolinate
- assessment scale
- controlled-trial
- tryptophan
- rat
- Psychiatry
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Brundin, L.
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Sellgren, C. M.
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Lim, C. K.
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Grit, J.
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Pålsson, Erik, 1 ...
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Landén, Mikael, ...
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Samuelsson, Mart ...
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Lundgren, Kristo ...
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Brundin, P.
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Fuchs, D.
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Postolache, T. T ...
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Träskman Bendz, ...
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Guillemin, G. J.
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Erhardt, S.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Translational Ps ...
- By the university
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University of Gothenburg
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Lund University
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Linköping University
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Karolinska Institutet