Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. By 2020, depression may be second only to heart disease as the leading cause of healthy years of life lost. Why is depression so common? Well, it’s said, “Nothing in Biology makes sense except in the light of evolution.” Why would we evolve to get depressed?

Depression presents a baffling evolutionary puzzle. Despite its negative effects, it remains common and heritable, meaning a large part of the risk is passed through our genes. Presumably, there must be some kind of adaptive benefit or it would have been naturally selected against. Could depression be an evolutionary strategy to provide a defense against infection? Infection has been the leading cause of mortality throughout human history, making it a critical force in natural selection. Indeed, because of infections, our average life expectancy before the industrial period was only 25 years, and it was not uncommon for half of our children to die without reaching adulthood.

When we become infected, there is a surge of inflammation as our body mounts a counter-attack. Our body responds by feeling lousy, sick, weak, tired, and slow. We don’t want to socialize. The only thing we do want to do is sleep. These symptoms are similar to the ones we experience during depression and are great for fighting infection. Slowing down not only helps us conserve energy to put up a good fight; it also reduces social contact so we don’t infect others. We see this protective phenomenon in other social animals, like honeybees and mole rats, who feel compelled to crawl off and die alone to reduce the risk of infecting the rest of their community. Humans have even evolved to think poop and decaying flesh don’t smell particularly good to keep us safe from infection.

To explore the relationship between inflammation and mental health, we have to look back to 1887, when this connection was first noted by Dr. Julius Wagner-Jauregg, the only psychiatrist to ever win the Nobel Prize. What evidence have we accumulated in the past century that inflammation causes depression? We know that people who are depressed have raised inflammatory markers, such as C-reactive protein and that inflammatory illnesses are associated with greater rates of major depression. Indeed, we find depression in even more benign inflammatory conditions such as asthma and allergies. This is important as it suggests that the mood symptoms may be directly tied to the inflammation and are not simply the result of “feeling bad about having a terrible disease.”

We also know that you can induce depression by inducing inflammation. For example, when we give interferon for certain cancers or chronic infection, up to 50 percent of people go on to suffer major depression. Even just giving a vaccine can cause enough inflammation to trigger depressive symptoms. Taken together, these studies “are strongly suggestive of inflammation being a causative factor of mood symptoms.”

Can an anti-inflammatory diet help prevent depression? We didn’t know until researchers followed the diets of about 43,000 women without depression for approximately 12 years. Those who ate a more inflammatory diet, characterized by more soda, refined grains, and meat, became depressed. “This finding suggests that chronic inflammation may underlie the association between diet and depression.”

Normally, we think of omega-3s as anti-inflammatory, but researchers found fish to be pro-inflammatory, associated with increased C-reactive protein levels. This is consistent with recent findings that omega-3s don’t seem to help with either depression or inflammation. As I discuss in my video Anti-Inflammatory Diet for Depression, the most anti-inflammatory diet is a plant-based diet, which is capable of cutting C-reactive protein levels by an impressive 30 percent within two weeks, perhaps because of the anti-inflammatory properties of the antioxidants found in plants. I talked about this in my Anti-Inflammatory Antioxidants video, but never explained why antioxidants are anti-inflammatory.

When free radicals cause oxidative damage, it may cause an autoimmune response in the body by changing the chemical structures of otherwise ubiquitous molecules to generate new structures that the body attacks as foreign. For example, when LDL cholesterol gets oxidized, our body creates antibodies against it that attack it. Likewise, clinical depression can be accompanied by increased oxidative stress and the autoimmune inflammatory responses it creates. Free radicals may thus lead to autoimmune inflammation.

Where else does inflammation in our diet come from? Endotoxins. It’s worth reviewing my videos on the subject—The Leaky Gut Theory of Why Animal Products Cause Inflammation, Dead Meat Bacteria Endotoxemia, and The Exogenous Endotoxin Theory—to see how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does this burst do to our mood? Within a few hours of injecting endotoxins, inflammation shoots up, increasing feelings of depression and social disconnection.

Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, only recently did research show the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli. In the study, subjects were injected with endotoxin. Within hours of the endotoxin hitting their bloodstreams, they began feeling depressed and had significant activity reductions in the reward center of the brain. The subjects, for example, were less excited about winning money playing video games. But as I discuss in my Plant-Based Diets for Improved Mood and Productivity and Antioxidants and Depression videos, we may be able to treat or even prevent depression by eliminating animal products and eating antioxidant-rich diets.

If you’re as much of a sucker for evolutionary biology theory as I am, you can learn more about it by checking out my High Blood Pressure May Be a Choice, The Problem with the Paleo Diet Argument, and Why Do We Age? videos.

I have several videos on inflammation, including:

And in Biblical Daniel Fast Put to the Test, I discuss a study that shows a dramatic decrease in inflammation within weeks on a plant-based diet.

For more information on the effect diet can have on mental health, check out:

In health,

Michael Greger, M.D.