Co-Morbidity between Cardiovascular Pathology and Depression: Role of Inflammation

Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that 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 are involved in and accountable for this co-morbidity in a major, complex and interactive way include the central and autonomic nervous systems, the neuroendocrine system, the immune system, and the vascular and hematologic systems. Specific pathophysiologic factors across these systems include homeostatic imbalance between the sympathetic and the parasympathetic systems with loss of heart rate variability in depression, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation resulting in hypercortisolemia, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoagulability. All of these abnormalities have been demonstrated in most individuals diagnosed with major depressive disorder. This chapter will focus on inflammatory processes. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression. A chronic pro-inflammatory status has been documented in numerous studies of depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. Endothelial dysfunction has been detected in depression and may prove to be a trait marker for this illness. Thus, understanding vascular biology in conjunction with psychiatric co-morbidity will be of critical importance. A likely common instigator underlying the co-morbidity between cardiovascular pathology and depression is mental stress. Chronic stress shifts the homeostatic balance in the autonomic nervous system with sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Antidepressant drug therapy is of definite benefit to patients with medical and psychiatric co-morbidity and may reverse the pro-inflammatory status associated with depression.