1

However, vascular disease, particularly the association between depression and heart disease, Is among the best-documented of all comorbidities.2 Not only writers and poets, but our language Itself refers to, “dying of a broken heart.” Almost all languages, In one way or another, express a very similar Idea. However, In spite of this widespread popular acceptance, Inhibitors,research,lifescience,medical scientific evidence has been slow In emerging, and has turned out to be of a more complicated nature than expected. Cardiovascular disease in depressed patients Early epidemiological studies relating melancholia to heart disease found much higher rates of cardiovascular deaths In melancholic patients, but their use of hospitalized Inhibitors,research,lifescience,medical populations confounded the effects of depression and chronic Institutionalization.3 After the Second World War, more psychoanalytic formulations, primarily “type A personality,” held sway. The time-urgent, angry, type A Individual did seem significantly more vulnerable to heart disease but by the inId497Qs the association became Increasingly difficult to replicate. Although we Inhibitors,research,lifescience,medical will never know for certain,

In retrospect it seems likely that the adverse consequences of the type A personality were real, but were mediated by the sympathetic nervous system.4 As cardiologists began to routinely use β-blockers after myocardial Infarct (MI), the significance of the type Inhibitors,research,lifescience,medical A personality dissipated. In

the mid-1970s, interest returned to the concept of major depression and cardiac disease or cardiac death. A Danish epidemiologist was the first to show that patients coming to treatment with a diagnosis of major depressive disorder (MDD) or manic-depressive disease were more likely to die from cardiac causes than the rest of the Danish population.5 Dozens of replications Inhibitors,research,lifescience,medical oxyclozanide have been reported, but it quickly became clear that these clinical populations confounded diagnosis and treatment. Using community, rather than clinical, samples circumvented the problem of treatment effect, because In community samples few cases were In treatment. The concern was that community cases as opposed to clinical cases of MDD would be considerably milder In severity, thereby masking the relationship. However, when the first community surveys appeared In the late 1980s the GABA activation relation-ship between major depression and cardiac death persisted.6 At the same time that these first community surveys began to appear, other studies were drawing attention to the relationship between MDD and cigarette-smoklng.