Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that contribute to this co-morbidity include the central and autonomic nervous systems, the neuroendocrine, immune, vascular and hematologic systems. Specific pathophysiologic factors include imbalance between the sympathetic and the parasympathetic systems, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoaguability. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression and in depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. A likely common instigator underlying this co-morbidity is mental stress leading to sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Stress hormones and certain pro-inflammatory substances released by macrophages and microglia upregulate the rate-limiting enzymes in the metabolic pathway of tryptophan. This results in a shunt in tryprophan metabolism away from serotonin formation and down the kynurenine pathway with resulting formation of neurotoxic metabolites.
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This work was partially supported by an intramural grant by Loyola University Chicago Stritch School of Medicine.
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Angelos Halaris declares that he has no conflict of interest.
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Halaris, A. Inflammation, Heart Disease, and Depression. Curr Psychiatry Rep 15, 400 (2013). https://doi.org/10.1007/s11920-013-0400-5