期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 48, 期 -, 页码 8-18出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2015.02.002
关键词
Major depressive disorders; Cardiovascular risk factors; Neuroendocrine; Stress; Cytokine; Corticosteroid receptor; Kynurenine
资金
- NIHR (National Institute for Health Research) Biomedical Research Centre (BRC)
- Dementia Unit at South London and Maudsley NHS (National Health Service) Foundation Trust and King's College London
- European Commission [EU-FP7-HEALTH-F2-2008-222963]
- British Council-Partek Partnership
- BHF (British Heart Foundation) - United Kingdom
- ECNP (European College of Neuropsychopharmacology)
- NARSAD (National Association for Research on Schizophrenia and Affective Disorders) Young Investigator Awards
- NIHR Programme Grants for Applied Research Programme (PGfAR)
- MRC [MR/J002739/1, G108/603] Funding Source: UKRI
- Medical Research Council [MR/J002739/1, G108/603] Funding Source: researchfish
Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n = 28) and without (n = 55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients. (C) 2015 The Authors. Published by Elsevier Inc.
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