Major depressive disorder and vascular diseases: The unbearable lightness of bidirectionality

Abstract

There is a generally accepted link between major depressive disorder (MDD) and atherosclerotic vascular disease (AVD). Depression is implicated as a risk factor for AVD, and patients with AVD manifest an increased incidence of MDD. Furthermore, MDD is understood to be a risk factor for increased mortality and morbidity after an acute coronary syndrome (ACS), and it is also associated with poor prognoses for stroke survivors and hypertensive patients. The link between MDD and AVD is not completely understood. MDD and AVD share some common physiopathological mechanisms including: hypothalamohypopheseal-adrenal axis and sympathomedullary hyperactivity, increased platelet reactivity, inflammatory response, oxidative stress, and endothelial dysfunction. Which mechanism is most prominent in the relationship is not known, or if it may vary from patient to patient. However, stress (particularly physiological stress) and endothelial dysfunction seem to both be influenced by the basic changes in inflammation, the autonomic nervous system, and the hypothalamic pituitary adrenal (HPA) axis, all of which bidirectionally affect each other. Although this incomplete knowledge does not explain the exact mechanism, each piece of data is important to the search for new treatment strategies. These strategies will improve treatments and prognoses, and will even aid the development of preventive approaches for people at risk of MDD and/or AVD by manipulating the various physiopathological mechanisms.