 Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. In fact, by 2020, depression may be the second leading cause of healthy years of life lost, second only to heart disease. Why is depression so common? Well, it is said nothing in biology makes sense, except in the light of evolution. But why would we evolve to get depressed? Depression poses a baffling evolutionary puzzle. If it has such negative effects, but yet it remains so common and irritable, meaning a big chunk of risk is passed through our genes. So there must be some kind of adaptive benefit. Otherwise, presumably, it would have been nationally selected against. Maybe depression is an evolutionary strategy for defense against infection. Infection has been the leading cause of mortality throughout human history. The average life expectancy was 25, and it was not uncommon for half our kids to die. With such stark capabilities, infection has been a critical and potent driving force in natural selection. When we become infected, there's a surge of inflammation as our body mounts a counter-attack. And then what happens? We feel lousy. We feel sick. We get weak, tired, slow, and sleepy. We don't want to see anyone. We don't want to do anything. All we want to do is sleep. It's like we're depressed. And that's great for fighting infection. Not only does it help us conserve energy so we can put up a good fight, but reduces social contact. We're not running around infecting everyone. It's the same reason we evolved to think, poop doesn't smell good or decaying flesh. That keeps us safe from infection. In fact, we see this phenomenon with other social animals almost like honeybees and mole rats, who feel impelled to crawl off and die alone when they get sick, which reduces the risk for the rest of the community. The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist ever win the award got a Nobel Prize. But what evidence have we accumulated in the century since that inflammation causes depression? Well, people who are depressed have raised inflammatory markers, such as C-reactive protein. Inflammatory illnesses are associated with greater rates of major depression. Indeed, that's what's found in a variety of inflammatory conditions, including more benign inflammatory conditions like asthma and allergies. And that's important, suggesting the mood symptoms are not simply feeling bad about having a terrible disease, but may be directly tied to the inflammation. And most powerfully, you can actually induce depression by inducing inflammation, like when we give interferon for certain cancers or chronic infections. Up to 50% 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 cause to factor of mood symptoms. So, can an anti-inflammatory diet help prevent depression? We didn't know until about 43,000 women without depression were followed along with their diets for about a dozen years to see who became depressed. And it was those who ate a more inflammatory diet pattern, characterized by more soda, refined grains, and meat, suggesting that chronic inflammation may underlie the association between diet and depression. Normally, we think of omega-3s as anti-inflammatory, but they found fish to be pro-inflammatory, associated with increased C-reactive protein levels, consistent with recent findings that omega-3s don't seem to help with either depression or inflammation. The most anti-inflammatory diet is plant-based, which can cut C-reactive protein levels by 30% within two weeks, perhaps because of the anti-inflammatory properties of antioxidants. I've talked about this before, but never really explain why antioxidants are anti-inflammatory. See, oxidative damage caused by free radicals may cause an autoimmune response in the body by changing the chemical structure 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 and attacks it. And so clinical depression can be accompanied by increased oxidative stress, and the autoimmune inflammatory response it creates. Free radicals lead to autoimmune inflammation. Where else does inflammation come from in our diet? Endotoxins. It's worth reviewing how the endotoxins in animal products can cause that burst of inflammation within hours of consumption. What does it do to our mood? If you inject endotoxin into people, within a few hours inflammation shoots up and so does feelings of depression, as well as feelings of social disconnection between people. Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, no work in humans has examined the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli. This is an important symptom of depression. No work has been done that is until now. Within hours of endotoxin hitting their bloodstream, these experimental subjects not only started to feel depressed, but they had significant reductions in activity in the reward center of their brain. They were less excited about winning money playing video games, for example, in this study. But by eliminating animal products and eating antioxidant-rich diets, we may be able to prevent or treat depression.