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

Raison, C L; Miller, A H

s of high infectious danger (including most psychosocial adversities) outweighed their cost in terms of any social impairment they incurred in these same contexts. A clear prediction of this hypothesis is that genes promoting inflammatory responses to psychosocial stress should decrease in prevalence over time in human societies in which the association between stressors and subsequent infection has been weakened by factors such as modern health practices. Consistent with this possibility, the prevalence of the short allele of the serotonin transporter gene, which has been associated with increased inflammatory responses to psychosocial stress, is lower in societies with reduced rates of historical infectious mortality. 104 In addition to providing a novel explanation for why stress is a primary risk factor for developing depression, the PATHOS-D theory offers a unifying perspective on why many other facets of modern life are also depressogenic, a perspective not readily provided by theories focused more exclusively on the social realm. Indeed, if the adaptive value of depression is to be found primarily in its effects on social functioning, it is hard to understand why so many risks for depression, including obesity, sedentary lifestyle, dietary factors, diminished sleep and smoking, are at least partially nonsocial in nature. On the other hand, these conditions are all associated with increased inflammation (for reviews see refs. 207, and 250-252), suggesting that they may be depressogenic because they tap into pathways that initially evolved to fight infection.