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

Raison, C L; Miller, A H

It should be noted that this Pathogen Host Defense (PAThos HOSt Defense = PATHOS-D) hypothesis is not the first theory to associate depression with protection from infection. Indeed, similar to PATHOS-D, at least one previous hypothesis has envisioned depression as a behavioral response that helps the immune system combat existing infections while avoiding additional pathogen exposure. 25 However, prior theoretical articulations have envisioned depressive symptoms as adaptive primarily because they compensate for various types of immune system vulnerabilities. 25 PATHOS-D suggests something qualitatively different and more far-reaching; specifically that depressive symptoms were integral components of immune-mediated host defense against pathogens in the ancestral environment. In this model, depressive symptoms are inextricably intertwined withand generated by-physiological responses to infection that-on average-have been selected as a result of reducing infectious mortality across mammalian evolution ( Figure 1 ). Thus, it is proposed that the alleles for depression, rather than having coevolved with immunological alleles that support pathogen defense, are in fact one in the same as those alleles, and therefore genes associated with depression would be predicted to be the same genes that are associated with successful host immune responses.