title: Ongoing episode of major depressive disorder is not associated with elevated plasma levels of kynurenine pathway markers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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".
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ringerike Psychiatric Center, Vestre Viken Hospital Trust, Drammen, Norway. Electronic address: johan.dahl@vestreviken.no.
authors.forename: Johan
authors.initials: J
authors.lastname: Dahl
authors.affiliation: 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.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Verkerk
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychosomatic Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Ulrik Fredrik
authors.initials: UF
authors.lastname: Malt
authors.affiliation: Center for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.affiliation: 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.
authors.forename: Lena
authors.initials: L
authors.lastname: Brundin
authors.affiliation: Faculty of Health Sciences, Buskerud and Vestfold University College, Drammen, Norway.
authors.forename: Heidi
authors.initials: H
authors.lastname: Ormstad
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000523:psychology*; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017378:Quinolinic Acid / Q000097:blood; D015398:Signal Transduction; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid
keywords: IDO; Inflammation; Kynurenic acid; Kynurenine; Major depressive disorder; Quinolinic acid