Serum kynurenic acid is reduced in affective psychosis

B. E. Wurfel, W. C. Drevets, S. A. Bliss, J. R. McMillin, H. Suzuki, B. N. Ford, H. M. Morris, T. K. Teague, R. Dantzer, J. B. Savitz

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative Nmethyl- D-aspartate (NMDA) receptor agonist. In contrast, schizophrenia and psychosis are hypothesized to arise from increased metabolism of the NMDA receptor antagonist, kynurenic acid (KynA), leading to hypofunction of GABAergic interneurons, the disinhibition of pyramidal neurons and striatal hyperdopaminergia. Here we present results that challenge the model of excess KynA production in affective psychosis. After rigorous control of potential confounders and multiple testing we find significant reductions in serum KynA and/or KynA/QA in acutely ill inpatients with major depressive disorder (N = 35), bipolar disorder (N = 53) and schizoaffective disorder (N = 40) versus healthy controls (N = 92). No significant difference was found between acutely ill inpatients with schizophrenia (n = 21) and healthy controls. Further, a post hoc comparison of patients divided into the categories of non-psychotic affective disorder, affective psychosis and psychotic disorder (non-affective) showed that the greatest decrease in KynA was in the affective psychosis group relative to the other diagnostic groups. Our results are consistent with reports of elevations in proinflammatory cytokines in psychosis, and preclinical work showing that inflammation upregulates the enzyme, kynurenine mono-oxygenase (KMO), which converts kynurenine into 3-hydroxykynurenine and quinolinic acid.

Original languageEnglish (US)
Article numbere1115
JournalTranslational Psychiatry
Volume7
Issue number5
DOIs
StatePublished - Jan 1 2017

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Psychotic Affective Disorders
Kynurenic Acid
Kynurenine
Quinolinic Acid
Psychotic Disorders
D-Aspartic Acid
Serum
Mood Disorders
Inpatients
Schizophrenia
Inflammation
Corpus Striatum
Oxygenases
Pyramidal Cells
Major Depressive Disorder
Interneurons
Bipolar Disorder
Up-Regulation
Depression
Cytokines

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Wurfel, B. E., Drevets, W. C., Bliss, S. A., McMillin, J. R., Suzuki, H., Ford, B. N., ... Savitz, J. B. (2017). Serum kynurenic acid is reduced in affective psychosis. Translational Psychiatry, 7(5), [e1115]. https://doi.org/10.1038/tp.2017.88

Serum kynurenic acid is reduced in affective psychosis. / Wurfel, B. E.; Drevets, W. C.; Bliss, S. A.; McMillin, J. R.; Suzuki, H.; Ford, B. N.; Morris, H. M.; Teague, T. K.; Dantzer, R.; Savitz, J. B.

In: Translational Psychiatry, Vol. 7, No. 5, e1115, 01.01.2017.

Research output: Contribution to journalArticle

Wurfel, BE, Drevets, WC, Bliss, SA, McMillin, JR, Suzuki, H, Ford, BN, Morris, HM, Teague, TK, Dantzer, R & Savitz, JB 2017, 'Serum kynurenic acid is reduced in affective psychosis', Translational Psychiatry, vol. 7, no. 5, e1115. https://doi.org/10.1038/tp.2017.88
Wurfel BE, Drevets WC, Bliss SA, McMillin JR, Suzuki H, Ford BN et al. Serum kynurenic acid is reduced in affective psychosis. Translational Psychiatry. 2017 Jan 1;7(5). e1115. https://doi.org/10.1038/tp.2017.88
Wurfel, B. E. ; Drevets, W. C. ; Bliss, S. A. ; McMillin, J. R. ; Suzuki, H. ; Ford, B. N. ; Morris, H. M. ; Teague, T. K. ; Dantzer, R. ; Savitz, J. B. / Serum kynurenic acid is reduced in affective psychosis. In: Translational Psychiatry. 2017 ; Vol. 7, No. 5.
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