Commenting on their hypothesis, Dr. Miller noted, "Most of the genetic variations that have been linked to depression turn out to affect the function of the immune system." Dr. Charles Raison of the University of Arizona added, "The basic idea is that depression and the genes that promote it were very adaptive for helping people -- especially young children -- not die of infection in the ancestral environment."

As recently as 1900, the top 3 causes of death in the U.S. were via infectious agents: pneumonia, tuberculosis, and diarrhea. Infants and young children were especially susceptible as 30.4% of all deaths occurred before the age of 5 years.

Thanks to improvements in public health and medicine (improvements like antibiotics), not a single one of the previous 3 leading causes of death are among the top 5 killers in the U.S today. Over the past century, infant mortality has dropped substantially, so that by 1997 only 1.4% of all deaths occurred before the age of 5 years. Although infection is no longer a top killer, infection was the primary cause of death for many of our ancestors.

Today, certain mutated versions of a gene called "NPY" are associated with increased inflammation (an immune process helpful in fighting off infections). Mutated NPY genes likely allowed our ancestors to better fight off infections (especially in childhood), and individuals with the mutated NPY gene were more likely to pass along the mutated NPY gene to offspring.

Interestingly, researchers at the University of Michigan's Molecular and Behavioral Neuroscience Institute discovered that individuals with major depressive disorder were more likely to have the mutated NPY gene. The normal NPY gene codes for higher levels of a neurotransmitter known as Neuropeptide Y, which appears to help ward off depression by increasing one's tolerance of stress. So the same mutated NPY gene that likely protected our ancestors against pathogens also increases our chance of developing depression.

Drs. Miller and Raison believe that acute (or severe but short-term) stress can not only lead to depression, but also jump-start the immune system. The physicians note that in the environments in which our ancestors lived, acute stress was often associated with the threat of physical harm or physical wounds. And unlike today, wounds readily led to infection and death. Therefore, Drs. Miller and Raison believe that evolution favored individuals whose immune systems operated under a "smoke-detector principle."

Although smoke detectors often react to false alarms (for me, burnt toast), if you removed the detector's battery and a real fire occurred, the consequences could be severe. Similarly, immune responses to acute stress are typically not necessary -- not every stressful situation results in a wound and infection. However, if our ancestors became wounded even a single time and didn't experience a piqued immune response, they might die from an infection.