The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)

Raison, C L; Miller, A H

The hypothesis that patterns of immune activity associated with MDD should have decreased mortality from infection in ancestral environments appears to face a challenge from data indicating that depression worsens outcome in a number of infectious processes [253] [254] [255] [256] [257] [258] [259] [260] and is associated with impairments in adaptive immune mechanisms important for protection against both viruses and bacteria. 13, 261, 262 To address this challenge, we have first to inquire whether innate immune inflammatory processes that are increased in MDD produce the patterns of infectious vulnerability and adaptive immune impairment that are apparent in depression. Surprisingly, the answer is yes. 263, 264 Although essential for activating adaptive immunity in response to pathogen invasion, chronic inflammation can actually suppress T-and B-cell function through various mechanisms. [263] [264] [265] [266] [267] [268] [269] [270] Consistent with this, rates of infection are often increased-not decreased-in autoimmune conditions characterized by chronic inflammation. 271 However, PATHOS-D theory requires only that across evolutionary time the survival benefits of enhanced inflammatory activity characteristic of depression outweighed any costs imposed by associated reductions in other aspects of immune functioning. Several lines of evidence support this possibility.