Out of all the clinical phenomena in psychology, depression holds the record for the largest number of evolution-based articles in the literature. This is most likely because it’s a very obvious paradox — how can a mood state which is so debilitating to genetic fitness (sufferers of major depression are more likely to lie in bed all day than to go seek a mate to begin a family) be so common (16.5% lifetime prevalence for Major Depressive Disorder according to NIMH, and much higher for subclinical occurrences)?
There’s a vast difference between normal depressed mood and major depression, and sometimes theorists are not as clear as they should be about which phenomenon they are attempting to explain — but at any rate, here are just some of the evolutionary explanations put forth for depression (not necessarily mutually exclusive):
- A functional submission/appeasement display
- A functional ruminative state to overcome social obstacles
- An aversive deterrent signal analogous to physical pain to help us avoid unpleasant situations
- A signal to the self to give up social goals which are going nowhere
- A social signal of helplessness to elicit help from friends/family
- A reaction to the loss of a newborn (in the case of postpartum depression)
- A result of mismatch between our ancestral environment and our current novel environment
I have no strong position for or against any of these particular arguments other than to say that elements of the mismatch hypothesis are very likely to be true to some extent — the social comparisons fostered by current global media have been a focus of traditional approaches to depression research to answer the question of why rates of depression seem to be growing. I may have a better body than most of my immediate crew of several dozen people, and I’m just fine about that…but once I see a photo of Ryan Reynolds shirtless, I get depressed at the comparison. Or so a specific example of the hypothesis goes.
I also should mention that most clinicians — even those with evolutionary leanings — generally tend to disfavor adaptationist hypotheses of depression, simply because of the exposure they have had to cripplingly despondent major depression patients. Both patient and clinician often have trouble accepting that there could possibly be anything functional about this state. I’m just telling you what people say. In general, these adaptationist hypotheses seem to fare better with low mood than with major depressive disorder itself, and most of these theorists realize this and allow that severe major depressive disorder represents a dysfunction rather than an adaptive state.
Anyway my friend Alice Andrews shared a paper which I missed, that came out early this year…a completely different type of evolutionary hypothesis to depression. The risk alleles for major depression, suggest authors Charles Raison and Andrew Miller, could be maintained because they’re also involved in pathogen host defense (or PATHOS-D, as they call their hypothesis) systems of the immune system. There have been long-recognized links between depression and immune response, after all, and depression has previously been suggested to be a functional behavioral state which assists the immune system as it does its work. The PATHOS-D hypothesis takes this one step further and suggests that the genes involved in depression are THE SAME as those involved in the immune response; hence, major depression has never been selected out of the gene pool.
As their support, Raison and Miller note that the three risk variant genes (or two SNPs and one gene, if you’re a genetics person) identified in genome-wide association studies all play important roles in immune response, including cytokine signaling and helper T cell function. Other genes which have been implicated in major depression in particular genetic studies are also noted by the authors to have obscure but real immunological functions. One gene of interest that caught my eye in the article was APOE, which is the most important known gene for Alzheimer’s dementia risk. Of the three common polymorphisms– named e2, e3, and e4 — e4 is the ancestral allele, but e2 and e3 confer some protection against Alzheimer’s dementia (e2 confers more protection than e3), but also — I just learned — against major depression. e2, however, is a risk factor for malaria and tuberculosis, while e4 is associated with inflammatory responses and protection against certain deadly childhood illnesses.
The authors note that depression is brought on by psychosocial stress, but that this fact is supportive of their hypothesis, since stressors in an ancestral environment (fear of a predator; interpersonal conflicts) would often have been accompanied by bodily injury and thus infection; therefore, stress responses can be seen as priming the inflammatory system (and thus accompanying depressive symptoms, say the authors). Since many of us no longer live in environments where stress reliably indicates impending injury, the authors suggest that depressive/immune response to psychosocial stress should be eventually selected against; in fact, they say, the short allele of the seratonin transport gene, which is associated with increased inflammatory response to stress, is less common in modern, relatively safe, societies.
The authors also note the similarities between “sick behavior” (which is associated with inflammatory/immune response) and depression, and note that patients who are receiving treatment with cytokine interferon-a (and thus have chronic immune activation) often meet criteria for major depression. But, in the “Limitations” section, they admit that not all major depressive patients show immune activation, and they suggest there may be other pathways leading to major depression.
This last part makes sense — I favor a model of severe depression as an end-state which can result from a number of different circumstances, including having chronic anxiety, suffering from a severe mental illness, being constantly unable to achieve particular social goals, or even — maybe — having an elevated immune response. Treatment implications are not a focus of the article, but if major depression is conceptualized as an autoimmune disorder like rheumatoid arthritis, lupus, or asthma, there are a number of testable predictions that could be made, and clinical trials could eventually be formulated around these.
I’ll admit that some of the biomolecular content of the piece was a little beyond me, so I am interested in anybody’s thoughts on the matter. However, I do think that the PATHOS-D hypothesis is one which is eminently testable and falsifiable. It’s also intriguing, and, if it stands up to the onslaught of scientific inquiry, could provide a whole host of answers and solutions to the medical and psychological communities.