Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders
| Autor: | Olav B. Smeland, Trude Seselie Jahr Vedal, Nils Eiel Steen, Srdjan Djurovic, Mikhail B. Bogdanov, Rima Kaddurah-Daouk, Erik G. Jönsson, Ingrid Dieset, Ingrid Melle, Sigrun Hope, Wayne R. Matson, Ole A. Andreassen, Ingrid Agartz |
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| Rok vydání: | 2019 |
| Předmět: |
Purine
Adult Male medicine.medical_specialty Kynurenine pathway Bipolar Disorder Adolescent Metabolite 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Internal medicine Medicine Humans Metabolomics Xanthurenic acid Vanillylmandelic acid Metanephrine Applied Psychology Kynurenine business.industry Tryptophan Middle Aged medicine.disease 030227 psychiatry Psychiatry and Mental health Endocrinology chemistry Psychotic Disorders Schizophrenia Tyrosine Female business 030217 neurology & neurosurgery Metabolic Networks and Pathways Blood sampling |
| Zdroj: | Psychological Medicine |
| ISSN: | 1469-8978 0033-2917 |
| Popis: | BackgroundWe aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls.MethodsPatients 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.ResultsSignificantly 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.ConclusionsAlthough 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. |
| Databáze: | OpenAIRE |
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