Did Depression Offer an Evolutionary Advantage?

A provocative new theory explores the possibility that depression is an evolutionary condition that protected our ancestors — from infection.

Such a theory could explain the ubiquity of depression which affects one in 10 adults in the United States. As such, experts believe the hypothesis that depression is “hard-wired” into our brains must be considered.

This has led biologists to propose several theories to account for how depression, or behaviors linked to it, can somehow offer an evolutionary advantage. Some proposals have focused on how depression influences behavior in a social context.

In a new article, a pair of psychiatrists addresses this puzzle in a different way, tying together depression and resistance to infection.

In this theory, researchers propose that genetic variations that promote depression also helped our ancestors fight infection. An outline of their proposal appears online in the journal Molecular Psychiatry.

Co-authors Andrew Miller, M.D., and Charles Raison, M.D., recognized that depression is often linked to inflammation or an overactivated immune system. People with depression tend to have higher levels of inflammation, even if they’re not fighting an infection.

“Most of the genetic variations that have been linked to depression turn out to affect the function of the immune system,” Miller said. “This led us to rethink why depression seems to stay embedded in the genome.”

“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, even if those same behaviors are not helpful in our relationships with other people,” Raison said.

Until development of sulfa drugs and antibiotics in the early part of the 20th century, infection was a major cause of death. Surviving infection was a key determinant in whether someone was able to pass on his or her genes.

The authors propose that evolution and genetics have bound together depressive symptoms and physiological responses that were selected on the basis of reducing mortality from infection. Fever, fatigue/inactivity, social avoidance and anorexia can all be seen as adaptive behaviors in light of the need to contain infection, they write.

The theory provides a new explanation for why stress is a risk factor for depression. In theory, the stress-depression link is a side-product of a process that pre-activates the immune system in anticipation of injury.

Similarly, a disruption of sleep patterns can be seen in both mood disorders and when the immune system is activated. This may come from our ancestors’ need to stay on alert to fend off predators after injury, Miller said.

Experts believe the new theory could also guide future research on depression. A particular area of focus could be the use of inflammation biomarkers to help predict whether someone will respond to various treatments for depression.

Miller and Raison are involved in ongoing research on whether certain medications, which are normally used to treat autoimmune diseases, can be effective with treatment-resistant depression.