Kynurenine and depressive symptoms in a poststroke population.

BACKGROUND AND PURPOSE: 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. PATIENTS AND 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-1ß) to anti-inflammatory (IL-10) cytokines compared. NLM IDENTIFIER: 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-1ß 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-1ß/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-1ß/IL-10 (ρ=0.43, P=0.001), as well as IL-1ß (ρ=0.29, P=0.04), were significantly associated with fatigue. CONCLUSION: 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.

The relationship between inflammatory markers and post stroke cognitive impairment.

OBJECTIVE: To determine whether there is a relationship between inflammatory markers (serum C-reactive protein (CRP) and cytokines) and post stroke cognitive impairment (PSCI). METHODS: This was a cross-sectional observational study. Patients were recruited from 4 sources: (1) the acute stroke unit of a general hospital, (2) an outpatient stroke prevention clinic, (3) a stroke rehabilitation unit in a specialized geriatric hospital, or (4) a stroke rehabilitation unit of a rehabilitation hospital. Patients meeting National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) project criteria for stroke were invited to participate in this study within the first 5 to 31 days post stroke. Patients with subarachnoid or intracranial hemorrhage, decreased level of consciousness, severe aphasia or dysarthria, or a significant acute medical, neurological, or psychiatric illness were excluded. Clinical assessments included the Mini-Mental State Examination (MMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of CRP, interleukin 6 (IL-6), and interferon gamma (IFN-gamma). RESULTS: A total of 48 patients with ischemic stroke (age [mean +/- SD] 71.6 +/- 13.2 years, 54.2% male, MMSE 26.4 +/- 3.8, NIHSS 6.8 +/- 4.0) were recruited within their first month post stroke. Backward stepwise elimination linear regression showed that higher concentrations of serum CRP (beta(CRP) = -0.46, p( CRP) = 0.002) predicted lower post stroke global cognition ([MMSE], F1,44 = 11.31, P = .002), with age (P = .92), level of education (P = .22), infarct side (P = 0.49), IL-6 (P = 0.36), and IFN-gamma (P = .57) removed from the final model. CONCLUSIONS: A post stroke inflammatory response may be important in subacute, PSCI.