Low Cortisol and Glucocorticoid Signaling But High Levels of Inflammation: Risk Factors for Developing Depression in Patients with Coronary Heart Diseases

sad heart

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.

Coronary heart disease (CHD) and major depressive disorders (MDD) are among the major causes of disability in developed countries.

There is a two-way relationship between heart disease and depression. People with depression develop heart disease at a higher rate than the general population. On the other hand, patients with established heart diseases have greater propensity to develop depression.

Moreover, inflammation is regarded as an important pathogenic factor in both CHD and MDD. Thus, inflammation is considered as one of the mechanisms involved in the association between these two debilitating diseases, and it has been implicated in the pathogenesis of depressive behaviors in CHD patients.

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.

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.

Source: Brain Behavior and Immunity, 2015. DOI: 10.1016/j.bbi.2015.02.002
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