Depression and immune function: central pathways to morbidity and mortality.

OBJECTIVE The increased morbidity and mortality associated with depression is substantial. In this paper, we review evidence suggesting that depression contributes to disease and death through immune dysregulation. METHOD This review focuses on recent human studies addressing the impact of depression on immune function, and the health consequences of those changes. RESULTS There is growing evidence that depression can directly stimulate the production of proinflammatory cytokines that influence a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. Additionally, depression can down-regulate the cellular immune response; as a consequence, processes such as prolonged infection and delayed wound healing that fuel sustained proinflammatory cytokine production may be promoted by depression. CONCLUSIONS These direct and indirect processes pose the greatest health risks for older adults who already show age-related increases in proinflammatory cytokine production. Thus, aging interacts with depression to enhance risks for morbidity and mortality.