The case for renaming depression an infectious disease

​According to the Canadian Mental Health Association, about 8 percent of adult Canadians will experience major depression at some time in their lives. And it's not always clear why. 

You believe we should re-brand depression as an infectious disease. Why?

One thing that the research field has noticed in recent years, starting about two decades ago, is that in many cases depression seems to be associated with some sort of inflammatory response of the body. So if you're looking for these molecules that signal some kind of illness, such as these molecules called cytokines, you notice that these seem to be elevated in depressed individuals. If you look at patients who are exposed to medications that boost immune system responses, for instance, 30% of those patients begin to show depressive symptoms that they didn't have before. So there is certainly a link to that - the question is, is the inflammation itself a causal contributor to the depression, which is what some people seem to be thinking, or is it really just a side effect of something else that causes inflammation? That is basically my hypothesis, that the inflammation that is correlated to depression is not really playing a causal role, it just happens to be a side effect of something else which is an infection, some sort of infection.

And what is it that we're talking about when we talk about inflammation?

There are many different ways in which the inflammatory system can be activated. So you could have coronary heart disease, you could have obesity, you could have rheumatoid arthritis, you could have stress, you could go through cancer therapy - any of those things can activate the immune system. Or, you could be exposed to some kind of pathogen such as a parasite or a bacterium or a virus. 

Let's try to understand the connection between the infection and the depression. Is there an evolutionary reason why depressive symptoms would come along with an infection? What's the benefit to the pathogen, or what's the benefit to the host?

The way I approached this question was to think of examples in nature that suggest how a pathogen might alter the behaviour or the brain of the host it's infecting.  Right now, we don't have any strong evidence for any of that as far as depression and humans is concerned. These are just clues that are out there in our understanding of biology and nature. One of them is an example that comes from the world of cats and rats. So there's a parasite that's called toxoplasma gondii or toxo for short. Toxo lives in the intestines of cats where it mates and lays its eggs. The eggs are then released into the environment through feline excretions, and now rodents can contact these eggs and become infected themselves. A very interesting thing happens when these rodents become infected. Instead of being afraid of the scent of cats, particularly cat urine, they become attracted to it. And so what happens is that the infected rat now seeks cats, which will then eat the rat and now the toxo that lived inside the rat found its way into a new home, into a new cat...The larger point I was trying to make in my paper was not so much to argue that any one specific example I gave was the explanation for depression, I think that is very naive. I think the larger point was to say let's start looking deliberately for other such examples, working specifically with large-scale, well-controlled studies involving depressed patients because that really hasn't been done yet.

Let's get back to the link between depression, inflammation and infection. Do you think pathogens are the most likely explanation for the prevalence of depression?

Depression is a really complex, multi-faceted illness. One way to think about it is to pick two patient experiences. On the one end, you may have a person who's had a hard life, somebody who's had to deal with traumatic abuse from early on in life, may continue to face chronic challenges day-to-day. Now take another example, of a patient who might tell you, I can't figure out what's wrong with me because I have everything - I have a job, I have a family, I have friends, I have people that love me - and yet I feel like something is missing, I feel like I'm worthless, I feel sad all the time, I can't stop crying and I don't know why. Those are two very different examples of patient profiles, and I would think that the latter one would be the more likely candidate to be examined for some sort of biological, pathogenic cause.

​And you see enormous hope around that. In light of your research, how would you like to see the thinking change around diagnosing and treating that latter kind of depression that you just described?

At some point in the future, we may actually have some sort of a lab panel that would be sent off for analysis that would look specifically for any number of different parasites, or bacterial or viral markers that would then tell the treating physician exactly what kind of treatment approaches should be used. So this would be a much more targeted approach. 

Do you think that there could be a cure for depression, if your hypothesis is correct?

To the extent that we could identify a very specific cause, I think that in principle a cure should be possible. Now, that is easier said than done. If you think about the HIV virus, we've known about its existence for three decades. We don't really have a cure, but we've made great strides and certainly in terms of managing it, we've made great strides. So I could imagine that something like that may be the case in other instances too, including depression.