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Psychoneuroendocrinology. 2015 Jun;56:12-22. doi: 10.1016/j.psyneuen.2015.02.011. Epub 2015 Feb 25.

Ongoing episode of major depressive disorder is not associated with elevated plasma levels of kynurenine pathway markers.

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Ringerike Psychiatric Center, Vestre Viken Hospital Trust, Drammen, Norway. Electronic address:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychosomatic Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Center for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
Department of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA; Van Andel Research Institute, Laboratory for Behavioral Medicine, Grand Rapids, MI, USA.
Faculty of Health Sciences, Buskerud and Vestfold University College, Drammen, Norway.



It has been suggested that the development of depressive symptoms as a result of cytokine therapy is attributable to cytokine-induced elevated activity of the kynurenine pathway. The few studies of this mechanism in patients with common major depressive disorder (MDD) have yielded inconsistent results. The aim of the present study was to identify markers of the kynurenine pathway in a clinical MDD sample with increased cytokine levels.


Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed for 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and their blood was analyzed for tryptophan and its metabolites in the kynurenine pathway. The clinical assessments and metabolite measurements were repeated after 12 weeks of "treatment as usual".


We did not find significant elevation of kynurenine plasma markers in patients with a depressive episode compared to healthy controls, despite elevated cytokine levels in the patients. Clinical depression scores were significantly reduced after 12 weeks, but no significant change in the plasma kynurenine pathway plasma markers was observed.


The obtained results do not support the hypothesis that MDD depressive episodes are associated with elevated activity in the kynurenine pathway. This suggests that the pathophysiology underlying depressive episodes in common MDD differs from that of interferon induced depression. Our results warrant further study of the interplay between the kynurenine pathway and the cytokine activation patterns in these conditions.


IDO; Inflammation; Kynurenic acid; Kynurenine; Major depressive disorder; Quinolinic acid

[Indexed for MEDLINE]

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