title: Connecting inflammation with glutamate agonism in suicidality.
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.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Erhardt
authors.forename: Chai K
authors.initials: CK
authors.lastname: Lim
authors.forename: Klas R
authors.initials: KR
authors.lastname: Linderholm
authors.forename: Shorena
authors.initials: S
authors.lastname: Janelidze
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.forename: Martin
authors.initials: M
authors.lastname: Samuelsson
authors.forename: Kristina
authors.initials: K
authors.lastname: Lundberg
authors.forename: Teodor T
authors.initials: TT
authors.lastname: Postolache
authors.forename: Lil
authors.initials: L
authors.lastname: Träskman-Bendz
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Lena
authors.initials: L
authors.lastname: Brundin
mesh_terms: D000328:Adult; D000368:Aged; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000523:psychology*; D018690:Excitatory Amino Acid Agonists / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007736:Kynurenic Acid / Q000134:cerebrospinal fluid; D007737:Kynurenine / Q000134:cerebrospinal fluid; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000523:psychology; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D020886:Somatosensory Disorders / Q000150:complications; D013129:Spinal Puncture; D013405:Suicide / Q000523:psychology*; D014316:Tritium / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D018690:Excitatory Amino Acid Agonists; D015850:Interleukin-6; D014316:Tritium; D007737:Kynurenine; D017378:Quinolinic Acid; D007736:Kynurenic Acid