It is well known that depression can be a consequence of medical illness and disability, but a growing literature suggests also that depression can cause biological changes linked to morbidity and mortality. Depression is strongly implicated as a contributor to cardiovascular disease and mortality. Using the cascade-to-death model as a conceptual framework, we explore the complex relations among behavior, affect, motivation, and pathophysiology that might account for the association between depression and premature death. Our model suggests that some individuals become entrapped in a downward spiral in which behaviour, medical illness, and depressive affect feed on each other to undermine the biological integrity of the organism. In addition to specifying behavioral and biological mechanisms linking depression to mortality, future research needs to more closely examine phenomenological aspects of depression in order to determine what aspects of depression and related constructs such as hopelessness, vital exhaustion, and motivational depletion account for the link between depression and mortality.
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