Why wasn’t major depressive disorder eliminated during evolution?

My posts have overwhelmingly focused on autism and schizophrenia, but my book also covers links between immune factors and major depressive disorder (MDD). However, an email from science writer Virginia Hughes stimulates me to write about MDD here. Ginny reminded me of a review published earlier this year by Charles Raison and Andrew Miller. In this article Raison and Miller seek to explain the persistence of variants of genes that increase the risk for MDD. Since debilitating MDD would seem to reduce the fitness for reproduction, why would such genetic variants continue to be carried in human populations? The usual answer to this type of question is that these variants must have some beneficial effects as well as negative effects. The classic example of this is sickle cell anemia, which is more common in parts of the world where malaria is endemic. In fact, there is evidence that carrying the risk gene for sickle cell (which is bad) makes the individual more resistant to malaria symptoms (which is good).

In the same vein, Raison and Miller make the argument that the genetic variants associated with increased risk for MDD are beneficial. Specifically, they point out that these variants are also “associated with immune responses to infection that were likely to enhance survival in the ancestral environment”. Indeed, as I point out in Chap. 7 of my book, there is considerable evidence of various types of immune associations with MDD, both in the blood and in the brain. Moreover, there are behaviors that are common between MDD and infection, or “sickness behavior”. These include survival-promoting symptoms such as fever (which stimulates the immune system and helps fight infection; and body temperature is generally elevated in subjects with MDD!), withdrawal from social contact (which could protect kin from infection and also make one less likely to be seen by predators), and hypervigilance (anxiety, agitation, insomnia would all help protect the individual from predators). Thus, MDD behavioral symptoms can be seen as evolutionarily beneficial and several of them help in fighting infection. Raison and Miller also point out that resistance to corticosteroids, which is common in MDD, is associated with improved immune function during HIV infection.

Thus, Raison and Miller have a number of interesting things to say about “the evolutionary significance of depression in pathogen host defense”.

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