A new Brain Behavior and Immunity study indicates that depression in coronary heart disease (CHD) is associated with high levels of inflammation in the context of low cortisol output and glucocorticoid receptor (GR) resistance.
The mechanisms associated with the link between the two diseases are not completely understood and identifying the pathophysiological mechanisms underlying the increased incidence of depression in patients with CHD remains a big challenge. Inflammation has been recognized as a common link between these two mental and physical disorders
Thus, inflammation is regarded as an important pathogenic factor in both CHD and MDD. Inflammation plays a central role in pathogenesis of CHD and is involved in all stages of atherosclerosis including initiation, propagation, and activation of atherosclerotic plaque, ultimately leading to thrombogenesis. Indeed, CHD patients show higher circulating pro-inflammatory cytokines, higher clinical markers of inflammation like C-reactive protein (CRP), and association with higher expression of inflammatory genes.
Downregulation of the anti-inflammatory cytokine IL-10 and upregulation of the pro-inflammatory cytokines IL-6 and TNF-α have been reported in chronic heart failurepatients with depressive symptoms, and patients with myocardial infarction have increased plasma IL-6 and CRP concentrations and altered response to the anti-inflammatory properties of glucocorticoids, which independently correlate with depressive symptoms.
In the Brain Behavior and Immunity study, Naghmeh Nikkheslat and colleagues from the Institute of Psychiatry, King`s College London, UK evaluated 83 coronary heart disease patients, with or without diagnosed depression, and assessed whether depressive symptoms correlate with inflammatory markers and abnormal hypothalamus-pituitary-adrenal (HPA) axis activity.
The authors found that CHD patients with depression had higher levels of C-reactive protein (CRP) and interleukin (IL)-6 gene expression, but lower levels of cortisol and glucocorticoid receptor (GR) mRNA, and less functional ability of the GR to respond to glucocorticoids.
They also showed that depressed CHD patients had reduced plasma levels of tryptophan and increased plasma levels of kynurenines, suggesting over activation of the serotonin degradation pathway.
The authors propose a model where the level of the endogenous cortisol is insufficient to limit inflammation in CHD patients with depression, due to hypoactivity of the HPA axis and GR resistance. Thus, chronic inflammation in patients with CHD may contribute to the development of depression, which in turn leads to further activation of inflammatory processes as reflected in joint elevation in IL-6 expression and CRP.
This, however, is inadequately restrained by endogenous glucocorticoids that are both lower and less able to act on the GR, and which lead to further brain and metabolic dysfunction by activating the kynurenine pathway.
This results in higher level of inflammation in these patients, which further maintains the GR resistance. All this may contribute to additional brain and metabolic dysfunction by over activation of the tryptophan/serotonin degradation (kynurenine) pathway.