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Psychol Med. 2019 Mar 14:1-12. doi: 10.1017/S0033291719000400. [Epub ahead of print]

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

Author information

1
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.
2
Bedford VA Medical Center,Bedford, MA,USA.
3
Duke Molecular Physiology Institute, Duke University,Durham, NC,USA.
4
Weill Medical College, Cornell University,New York,USA.

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:

Metabolomics; psychotic disorders; tryptophan; tyrosine

PMID:
30867076
DOI:
10.1017/S0033291719000400

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