Connecting inflammation with glutamate agonism in suicidality

Sophie Erhardt, Chai K. Lim, Klas R. Linderholm, Shorena Janelidze, Daniel Lindqvist, Martin Samuelsson, Kristina Lundberg, Teodor T. Postolache, Lil Träskman-Bendz, Gilles J. Guillemin, Lena Brundin*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    201 Citations (Scopus)
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    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<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.

    Original languageEnglish
    Pages (from-to)743-752
    Number of pages10
    JournalNeuropsychopharmacology
    Volume38
    Issue number5
    DOIs
    Publication statusPublished - Apr 2013

    Bibliographical note

    Copyright the Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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