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The New Thinking on Depression, According to an Expert

Inflammation in the body is linked with a host of ills: cancer, heart disease, obesity, autoimmune disorders, digestive diseases, to name some of the biggies. And if you had any of those diseases, it’s only logical you’d feel bummed out, and possibly depressed.

Most Men Don’t Realize They’re Depressed. Here’s How to Recognize the Signs and Seek Help.

But what if depression isn’t always a logical reaction to illness, or even to stress? Edward Bullmore, professor of psychiatry at the University of Cambridge, in the U.K., proposes that for some, depression is actually the direct result of inflammation—which helps explain why, for some, the typical treatments (medication, talk therapy, even deep brain stimulation for severe cases of depressive disorder) provide incomplete or fleeting relief. We asked Bullmore about his startling theory.

It’s hard to overstate how pivotal—and potentially controversial—this theory is. What led you to theorize that inflammation and depression were related?I saw a patient with arthritis in 1989— arthritis is inflammation of the joints. She was the first person I had where it was clear to me she was both inflamed and depressed. I asked the clinician in charge what he thought. He said, “Depressed? Of course she is. Wouldn’t you be?” And that was that. Depression was considered a normal emotional reaction to not feeling well.

It sounds like you had an inkling that inflammation caused the arthritis and depression separately, rather than the inflammation causing arthritis, leading to depression. How does that work?Inflammation is established science. Following certain diseases, trauma, or stress, the body has a natural inflammatory response to it. But unchecked or long-lasting inflammation is dangerous. The theory is that immune cells release proteins known as cytokines, which send an inflammatory signal to the brain. The brain’s immune cells may begin to produce cytokines themselves, which interfere with the brain’s ability to use serotonin.

And this is why meds don’t always work.Yes. If the brain is having trouble using serotonin—a feel-good chemical—anti- depressant drugs like SSRIs that are sup- posed to boost serotonin won’t be effective.

That seems to make sense.Yes, but it’s based on new knowledge about the relationship between the immune and nervous systems. In the 1980s, it was regarded as medical fact that the blood-brain barrier protected the brain from inflammatory proteins and immune cells circulating in the blood. Through advancements in science and technology, we now know there are many ways inflammatory cell signals can get across the barrier.

Does this mean everyone who is depressed is experiencing some kind of inflammation?No. Not everyone who is inflamed is depressed, and not everyone who is depressed is inflamed. We need to move away from the idea that depression is the same thing for everyone, and there is only one treatment for it. That’s the mindset we’ve been stuck in for 40 or 50 years.

How has this impacted our understanding of depression?Well it’s certainly influenced how drug treatments have been developed, and why successful therapy innovation has stalled.

The medications have worked somewhat, or people wouldn’t continue to use them, right?It is clear SSRIs work moderately well, on average. The key phrase is “on average.” What that conceals is that for some depressed people, they work really well. But for others, they don’t work at all.

How long until we have new depression drugs that target inflammation?I am cautious about making predictions. The process is long and complicated. There are some clinical trials with people who have arthritis and other inflammatory diseases, and seeing how levels of fatigue and depression respond to inflammation-targeting drugs. For them, we’re maybe five years away from seeing a treatment approved. For the broader group, it will take longer.

What’s the ultimate goal?There needs to be more than one approach to treating depression. There are clearly individual differences in how patients respond to treatment. In terms of inflammation, whether it leads to depression in some people and not others may be tied to differences in genetic makeup, or possibly related to life-experience differences.

For now, what can we do with this knowledge?Patients and physicians alike need to reconsider what “going to the doctor” looks like. Seeing one doctor for mental health and another for physical health, as if these are two completely different things, is a disadvantage to patients dealing with both types of issues. Unfortunately, that’s how the system is set up. It’s up to the patient to consider if how he feels physically and his mental state are connected.

And if he thinks they are?Look at various things that can lead to inflammation: diet, exercise, and stress. Practicing stress-reducing techniques might also have an antidepressant effect. There is not one single way to treat depression, but these are some ways to start.

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