Title:Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder
VOLUME: 20 ISSUE: 15
Author(s):Alexander Maget, Martina Platzer*, Susanne A. Bengesser, Frederike T. Fellendorf, Armin Birner, Robert Queissner, Carlo Hamm, Bernd Reininghaus, Andrzej Hecker, Lukas Tomberger, Renè Pilz, Nina Dalkner, Natalie Moll, Gregor Schütze, Markus Schwarz, Hans P. Kapfhammer and Eva Z. Reininghaus
Affiliation:Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Institute of Laboratory Medicine Medical Center of Munich University (LMU), Munich, Institute of Laboratory Medicine Medical Center of Munich University (LMU), Munich, Institute of Laboratory Medicine Medical Center of Munich University (LMU), Munich, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz
Keywords:Bipolar disorder, Kynurenine, Pteridines, Inflammation, Mood, Depression, Mania.
Abstract:
Background & Objective: The kynurenine pathway is involved in inflammatory diseases. Alterations
of this pathway were shown in psychiatric entities as well. The aim of this study was to determine
whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar
disorder.
Methods: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania
Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and
euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated
with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/
kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of
3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations.
Results: Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase
activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no
differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within
the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a
significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of
kynurenic acid.
Discussion: Depression severity in bipolar disorder seems to be associated with a decreased synthesis of
putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently
manic individuals indicates an increased inflammatory state within bipolar disorder with more severe
inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective
episodes could represent parallel mechanisms rather than opposed processes.
