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Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders

Published online by Cambridge University Press:  14 March 2019

Nils Eiel Steen Open the ORCID record for Nils Eiel Steen [Opens in a new window] ,
Ingrid Dieset ,
Sigrun Hope ,
Trude S.J. Vedal ,
Olav B. Smeland ,
Wayne Matson ,
Rima Kaddurah-Daouk ,
Ingrid Agartz ,
Ingrid Melle  and
Srdjan Djurovic
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Nils Eiel Steen*
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Ingrid Dieset
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Sigrun Hope
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway
Trude S.J. Vedal
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Olav B. Smeland
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Neuroscience, University of California San Diego, La Jolla, CA92093, USA
Wayne Matson
Affiliation:
Bedford VA Medical Center, Bedford, MA, USA
Rima Kaddurah-Daouk
Affiliation:
Duke Molecular Physiology Institute, Duke University, Durham, NC, USA Duke Institute of Brain Sciences, Duke University, Durham, NC, USA Department of Medicine, Duke University, Durham, NC, USA
Ingrid Agartz
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Ingrid Melle
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Srdjan Djurovic
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Medical Genetics, Oslo University Hospital, Oslo, Norway Department of Clinical Science, University of Bergen, Bergen, Norway
Erik G. Jönsson
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
Mikhail Bogdanov
Affiliation:
Weill Medical College, Cornell University, New York, USA
Ole A. Andreassen
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
*
Author for correspondence: Nils Eiel Steen, E-mail: n.e.steen@medisin.uio.no
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Abstract

Background

We aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls.

Methods

Patients with schizophrenia and bipolar disorders (N = 212) and healthy controls (N = 68) had blood sampling with subsequent metabolomics analyses using electrochemical coulometric array detection. Concentrations of 52 metabolites including tyrosine, tryptophan and purine pathways were compared between patients and controls while controlling for demographic and clinical characteristics. Significant findings were further tested in medication-free subsamples.

Results

Significantly decreased plasma concentrations in patients compared to healthy controls were found for 3-hydroxykynurenine (3OHKY, p = 0.0008), xanthurenic acid (XANU, p = 1.5×10−5), vanillylmandelic acid (VMA, p = 4.5×10−5) and metanephrine (MN, p = 0.0001). Plasma concentration of xanthine (XAN) was increased in the patient group (p = 3.5×10−5). Differences of 3OHKY, XANU, VMA and XAN were replicated across schizophrenia spectrum disorders and bipolar disorders subsamples of medication-free individuals.

Conclusions

Although prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders. Of special interest is XANU, a metabolite previously not found to be associated with bipolar disorders.

Keywords

Metabolomicspsychotic disorderstryptophantyrosine
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 4 , March 2020 , pp. 595 - 606
Copyright
Copyright © Cambridge University Press 2019

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