Current understanding of the bi-directional relationship of major depression with inflammation

Evidence shows an association of major depression with increased risk for adverse physical health outcomes. Indeed, depression, whether assessed as a continuum of symptoms or as the presence of a clinical syndrome, predicts the incidence and progression of diseases of aging, including cardiovascular, metabolic and neurodegenerative diseases, as well as all-cause mortality [1-3]. Given the burden of these physical illnesses, it is not surprising that affective symptoms and disorders are more prevalent among the medically-ill than the general population [4,5], raising the possibility that associations between affective disorders and physical health are bi-directional in nature. It is also likely that lifestyle choices contribute to poorer health among individuals with depression [6]; however, to date, evidence suggests that behavioral factors contribute only minimally to depression-related variability in health risk. Thus, other mechanisms must also be operating. Accumulating evidence suggests that the immune system may play a role.Early studies show an association of depression with the down-regulation of functional parameters of the immune system (for example, decreased ability of NK cells to destroy tumor cells [7]). However, this immune suppression is not as 'global' as initially proposed. Indeed, recent attention has focused on the activation of innate, non-specific inflammatory mechanisms that also accompany depressed mood [8]. These differential immune responses to negative mood have been interpreted within an evolutionary context as a down-regulation of processes that take time and energy in favor of an up-regulation of processes that are immediately available to defend the organism [9]. Although adaptive and of potential health benefit in the short-term, growing evidence shows that chronic elevation of inflammation plays a role in the pathogenesis and course of numerous age-related physical health conditions, possibly contributing to the co-morbidity of depre