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

Raison, C L; Miller, A H

As suggested above, anorexia may enhance survival during infection by redirecting energy away from food procurement to the metabolic demands of immune activation/fever, while also limiting the exposure to food-borne pathogens. But the metabolic requirements of fighting infection make the anorexic response a paradox in need of a more robust adaptive explanation. Although it remains unclear whether food restriction protects against the development of infection, 377 animal data indicate that force feeding rodents once they are infected increases mortality. 378 Similarly, the provision of total parenteral nutrition in animal models and to critically ill patients has been associated with increased risk for infection and subsequent mortality. [379] [380] [381] [382] Interestingly, rats injected with lipopolysaccharide consume proportionately more carbohydrates-as do depressed individuals with hyperphagia 383 -even though more energy is available from ingesting lipids. This suggests that lipid consumption may be counterproductive during an infection. Several observations are consistent with this possibility. For example, preclinical data demonstrate that lipid consumption increases infectious mortality, 384 and a meta-analysis of total parenteral nutrition use found that infected patients provided lipids in their feedings had higher complication rates than those receiving total parenteral nutrition without lipids. 385 Finally, omega-3 fatty acids have been shown to activate peroxisome proliferator-activated receptor-g signaling in dendritic cells, with a resultant downregulation of CD1a receptor expression. 129 These receptors play an essential role in activating T-cell responses to pathogens, as demonstrated by the ability of Leishmania donovani to survive in host cells by downregulating these receptors. 386 Moreover, CD1a expression in dendritic cells is also crucial for the presentation of M. tuberculosis antigens to cells of the adaptive immune system. 387 Potential limitations of, and challenges to, PATHOS-D theory