Kynurenine and depressive symptoms in a poststroke population

Abstract

Background and purposeDepression 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.Patients and methodsThis 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.NLM identifierNCT00254020.ResultsIn 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 (F2,76=0.04, P=0.96) controlling for relevant covariates. For cytokines (n=53), serum IL-1β concentrations (F2,52=3.55, P=0.037) and serum ratios of IL-18/IL-10 (F2,52=3.30, P=0.046), IFNγ/IL-10 (F2,52=4.02, P=0.025), and IL-1β/IL-10 (F2,52=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.ConclusionPeripheral 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.

Bidirectional psychoneuroimmune interactions in the early postpartum period influence risk of postpartum depression

“…While pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, and IL-6 coordinate the non-specific (inflammatory) immune responses, anti-inflammatory cytokines such as interleukin IL-10 not only provide negative feedback to limit inflammation, but also support development of a type 2, or specific immune response (Petrovsky and Harrison, 1997). The findings in this study emphasize the importance of the interplay between these two arms of the immune response to affect mood, and mirror findings from other studies emphasizing the importance of considering pro- to anti-inflammatory cytokine ratios when evaluating risks for depression (Bensimon et al, 2014; Fredericks et al, 2010). And lastly, the variability in previously published findings on inflammation and PPD may be due as well to the timing of sample collections, the sources of sample, or the inclusion of women with confounding perinatal experiences such as surgical birth or transfusion, or co-morbidities known to affect the immune system or mood.…”

Post-stroke Fatigue and Depressive Symptoms Are Differentially Related to Mobility and Cognitive Performance

“…Some evidence suggests that inflammation might also contribute to post-stroke cognitive impairment (Rothenburg et al, 2010 ; Gold et al, 2011 ; Di Napoli et al, 2012 ; Slevin et al, 2015 ). An inflammatory hypothesis for post-stroke depression yielded both positive (Yang et al, 2010 ; Jiao et al, 2016 ) and negative (Noonan et al, 2013 ; Bensimon et al, 2014 ) results, as reviewed previously (Becker, 2016 ); recent studies suggest a more robust relationship between inflammation and fatigue (Bensimon et al, 2014 ), which might be useful to direct future intervention trials (Barritt and Smithard, 2011 ). For instance, although fluoxetine treatment alleviated post-stroke depression, it did not improve fatigue (Choi-Kwon et al, 2007 ), whereas treatment for, or successful resolution of, depressive symptoms tend to improve cognition (Doraiswamy et al, 2003 ).…”

“…The Center for Epidemiological Studies Depression scale (CES-D) is a 60-point self-report instrument that assesses the presence and severity of depressive symptoms over the past week, used extensively in stroke (Bensimon et al, 2014 ; Swardfager et al, 2014 ). The Fatigue Assessment Scale (FAS) is also a self-report instrument used in stroke research (Duncan et al, 2015 ), with 10 items to score aspects of fatigue, each rated from 1 to 5.…”

The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

“…Several clinical studies in the stroke field have tried to evaluate the role of KP in post-stroke depression and its relation to pro-inflammatory markers, given that inflammation is also commonly observed in depressive patients. Unfortunately, aforementioned studies did not find a correlation between peripheral L-Kyn/L-Trp ratios and depressive symptoms in the post-stroke population [202, 203]. However, several interesting results were observed in these studies.…”