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Connecting Inflammation with Glutamate Agonism in Suicidality

Erhardt, Sophie ; Lim, Chai K. ; Linderholm, Klas R. ; Janelidze, Shorena LU ; Lindqvist, Daniel LU ; Samuelsson, Martin ; Lundberg, Kristina ; Postolache, Teodor T. ; Träskman Bendz, Lil LU and Guillemin, Gilles J. , et al. (2013) In Neuropsychopharmacology 38(5). p.743-752
Abstract
The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the... (More)
The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (P<0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013 (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
quinolinic acid, suicide, depression, glutamate, cytokine
in
Neuropsychopharmacology
volume
38
issue
5
pages
743 - 752
publisher
Elsevier
external identifiers
  • wos:000316161300004
  • scopus:84875211649
  • pmid:23299933
ISSN
1740-634X
DOI
10.1038/npp.2012.248
language
English
LU publication?
yes
id
73928677-4f88-4618-a896-f3915564778a (old id 3636081)
date added to LUP
2016-04-01 10:51:37
date last changed
2022-05-18 02:33:50
@article{73928677-4f88-4618-a896-f3915564778a,
  abstract     = {{The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (P&lt;0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013}},
  author       = {{Erhardt, Sophie and Lim, Chai K. and Linderholm, Klas R. and Janelidze, Shorena and Lindqvist, Daniel and Samuelsson, Martin and Lundberg, Kristina and Postolache, Teodor T. and Träskman Bendz, Lil and Guillemin, Gilles J. and Brundin, Lena}},
  issn         = {{1740-634X}},
  keywords     = {{quinolinic acid; suicide; depression; glutamate; cytokine}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{743--752}},
  publisher    = {{Elsevier}},
  series       = {{Neuropsychopharmacology}},
  title        = {{Connecting Inflammation with Glutamate Agonism in Suicidality}},
  url          = {{http://dx.doi.org/10.1038/npp.2012.248}},
  doi          = {{10.1038/npp.2012.248}},
  volume       = {{38}},
  year         = {{2013}},
}