We know that the brains of people with depression are different from the brains of healthy people in both their chemical balance and structure, but despite the fact that roughly 10 percent of the U.S. population struggle with the disease, scientists know startlingly little about why these changes occur.
Clinical depression -- also known as Major Depressive Disorder (MDD) -- is thought to be caused by a combination of genetic, environmental, psychological and biological factors. But one psychologist believes we've overlooked biological factors that may be the missing piece of the puzzle.
In a provocative new paper, Dr. Turhan Canli, associate professor of integrative neuroscience at Stony Brook University, makes a case for reconceptualizing depression as an infectious disease caused by foreign invaders like parasites, bacteria or viruses that make their way into the body and cause changes in the brain.
The paper, recently published in the journal Biology of Mood & Anxiety Disorders, highlights three different avenues through which infections could cause depression, looking to existing examples of parasites, bacteria and viruses that have been found to affect mood and behavior.
The Huffington Post spoke to Canli about his theory and what it might mean for future treatment.
What depressive symptoms point towards a possible origin in infectious disease?
The biggest clue is that depression is often associated with inflammation. And inflammation can come from different sources -- it doesn't have to be an infection -- but for me, it's the most intuitive way to think about why one would have some sort of infection. It would be the activation of the immune system to some sort of infectious disease. The field overall is accepting of the notion that inflammation may play a role in depression, but the idea that [depression] could actually be something very specific that comes from parasites or bacteria or viruses -- that's still new.
If you take that as a possibility, it opens up new ways of thinking about the disease, and it opens up new approaches to the research, too. That's what's useful right now.
If we're wrong about what causes depression, how come treatment so often works?
The model for the past 60 years is that depression is an emotional disease that's tied to the brain. That's been useful up to a point. So for instance, we identified neurotransmitters that are deregulated in people with major depression -- primarily serotonin -- and so basically all of the serotonin uptake inhibitor [medications] come out of that discovery. We've learned a little bit about particular brain areas that are involved in depression, and noticed structural changes in these brain regions. Now it seems that we've been stuck, we haven't progressed much past those discoveries.
When you look at the success of the medications that have been developed over the past six decades, there hasn't been much movement. Those medications are not necessarily more effective than they were 20 or 30 or 40 years ago. I think it is in part because we're not understanding why these neurotransmitters are different and why these brain regions do change. We don't really understand the underlying mechanisms.
In what cases have we seen infectious agents affect mood and behavior?
There's some literature on intestinal bacteria and probiotics. We have more than 1,000 strains of bacteria in our intestines, and it turns out that you need those to digest food. They may also play a role in our emotional states, so that people who have experienced negative emotions report improved mood when placed on a probiotic. These people may experience a reduction in depressive symptoms and anxious symptoms. So that's one example of bacteria playing a role in mood.
There's some work on animals that goes more deeply into the potential mechanisms. There are mice that were bred to have no intestinal bacteria -- so these are germ-free, super clean mice. When you take them into a laboratory setting where you stress them out, they show a very strong stress response. But when you then put them on a diet of common intestinal bacteria, their stress response normalizes. So there's a possibility that these bacteria that we have in our guts may not only help us digest our food, but may also play a role in our emotional well-being. You could flip that upside down and say, well there's good bacteria, but maybe there's also bad bacteria that instead of lifting your mood could depress your mood...
There was one epidemiological study that looked at the prevalence of a particular parasite across 20 different European countries, and they correlated that with suicide rates, and they found a significant positive correlation. Now, we all know from any introductory science course that correlation isn't causation, so we don't know what the deal is with that, but there is a correlation there. It's also correlated with higher levels of self-reported neuroticism as a personality trait... This is all very preliminary, but I think it might be one interesting starting point.
What about the argument that depression is genetic?
We know that for major depression, environmental factors are hugely important. If somebody has a really hard life and terrible things happen to them, they're likely to become depressed. But there's also some contribution from genetic factors, and yet when we look for those genetic factors, we have a tough time finding them. There's a serotonin transporter gene that has a variation, so that seems to be associated with depression through life stress. But other than that, we haven't really been able to come up with a list of genes that are tightly linked to depression.
One way to think about the possibility of the human as an ecosystem, or a host for microorganisms, is to think that maybe we've looked at the wrong genome. Maybe it's about the genes of these parasites and bacteria and viruses inside of us that might be predictive of depression.
What would depression treatment look like in a world where we targeted a microbiome instead of brain chemistry?
In more concrete, clinical terms, what it could mean for a patient is that if any of this were true, then at some point we might actually know what microoganisms to look for. The first thing that you might do when you see a psychiatrist and complain about depressive symptoms is that they might give you a blood test to see if you have any of those microorganism biomarkers, and they would treat you accordingly. This would be very different from the way it is now, which is trial and error.
This interview has been edited and condensed for clarity.