title: Kynurenine and depressive symptoms in a poststroke population.
abstract: OBJECTIVE
  Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.
  
  
  METHODS
  This was a multisite cross-sectional observational cohort study of patients with ischemic stroke. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression (CES-D) scale and divided into high, medium, and low depressive symptom tertiles. Concentrations of kynurenine and tryptophan were assayed from fasting serum samples, and the kynurenine/tryptophan ratio was compared between tertiles. Serum cytokine concentrations were assayed in a subgroup of patients, and the ratio of proinflammatory (IL-6, IL-18, IFNγ, TNF, IL-1β) to anti-inflammatory (IL-10) cytokines compared.
  NCT00254020.
  
  
  RESULTS
  In these patients (n=86, 52.3% male, mean age 71.7±14.2 years), there were no differences in kynurenine/tryptophan ratios between CES-D scale tertiles (F 2,76=0.04, P=0.96) controlling for relevant covariates. For cytokines (n=53), serum IL-1β concentrations (F 2,52=3.55, P=0.037) and serum ratios of IL-18/IL-10 (F 2,52=3.30, P=0.046), IFNγ/IL-10 (F 2,52=4.02, P=0.025), and IL-1β/IL-10 (F 2,52=4.34, P=0.019) were elevated in the middle CES-D tertile. Post hoc analyses suggested that serum ratios of IL-18/IL-10 (ρ=0.28, P=0.04), and IL-1β/IL-10 (ρ=0.43, P=0.001), as well as IL-1β (ρ=0.29, P=0.04), were significantly associated with fatigue.
  
  
  CONCLUSIONS
  Peripheral kynurenine/tryptophan ratios were not associated with depressive symptoms in a poststroke population. However, in exploratory analyses a proinflammatory bias was identified specifically in patients with mild depressive symptoms and associated with poststroke fatigue, suggesting an avenue for future research.
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Kira
authors.initials: K
authors.lastname: Bensimon
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Toronto Rehabilitations Institute,Toronto, ON, Canada ; Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Yi
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Toronto Rehabilitations Institute,Toronto, ON, Canada ; Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON, Canada.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Gao
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Toronto Rehabilitations Institute,Toronto, ON, Canada.
authors.forename: Abraham
authors.initials: A
authors.lastname: Snaiderman
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Toronto Rehabilitations Institute,Toronto, ON, Canada ; Canadian Partnership for Stroke Recovery, Heart and Stroke Foundation, Ottawa, ON, Canada.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
keywords: cytokine; depression; inflammation; kynurenine; stroke; tryptophan