Using Hyperthermia as Antidepressant Treatment

In part 1 of this interview, Charles Raison, MD, a psychiatry professor at the University of Wisconsin — Madison, discusses the results of his recent study “Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder," which investigated hyperthermia as a treatment for major depressive disorder (MDD). Dr Raison examines the study parameters, hyperthermia mechanisms of action, and what clinicians can glean from the results. 

See what else Dr Raison had to say in part 2: Frontiers in Psychiatry: Heat, Cold, and Psychotherapy

TRANSCRIPTION:

What were the key findings of your recent study “Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder?”

Chuck Raison, MD: My colleagues and I have been at the forefront of studying heat as an antidepressant—we call it hyperthermia. We do it with a machine, and it's called whole-body hyperthermia. We take people that are very depressed and we stick them in this machine and it raises their body temperature, and we try to raise their body temperature up to 101.3 degrees Fahrenheit. We've shown that that produces a rapid and long-term antidepressant response. It's really quite striking. It's a real response and we have a beautiful placebo condition that is very believable, does not do the same thing. So we know there's something about heat that is an antidepressant. So then of course it raises an immediate question, okay, well, what's heat doing that would make it an antidepressant?

I've done a lot of work on the relationship between inflammation and depression, and we know that when people become inflamed, when these things called cytokines rise up in their blood, they get into the brain and they change brain function in ways that make people anxious and depressed. So these are bad actors. And there's a famous bad actor, it's a cytokine, it's called interleukin-6, and I'm going to call it IL-6. So if you're walking around with increased IL-6, you're more likely to be depressed, you're more likely to get depressed, you're more likely to develop diabetes, you're more likely to die of a heart attack, you're more likely to become demented when you get old, you're more likely to have a stroke, bad actor. If your IL-6 is up, your brain is shrunk. We can go on and on about how terrible this thing is.

But there's an intriguing little twistedness, which is that if you take something like exercise, which we know is an antidepressant, and if you measure IL-6 in the blood with exercise, what you see is that it doesn't go down, it shoots way up and then comes back down again. When we did the hyperthermia study in depression, I was naively thinking, well, it's just going to lower things like IL-6 because they're bad. So if this works, it's going to push them down. So we measured IL-6, we looked at IL-6 right before people got this heat treatment, right after, a week after, and 4 weeks after. And contrary to our expectations, we saw something that was quite remarkable. Hyperthermia just ramps up this nasty thing called IL-6. So, darn, you know? And then within a week it's back to normal.

Then we said, well, man, that's weird. IL-6 is bad. I bet that people that got undepressed, maybe they get less IL-6. It went up. We looked and we found exactly the opposite. We found that the more the IL-6 went up, the more the depression went down over the subsequent 6 weeks. This is really, really interesting. It's really interesting if you're into what's called psychoneuroimmunology because it flies in the face of what we tend to think. Again, it just points to how complex life is. But it's also what you see with exercise. So hyperthermia, heat, saunas, things like this, they produce an effect in the body that is very, very similar to what you see. If you went out and ran a couple of miles, and this seems to be a signature of treatments that are stressors. So they're not relaxation, when I put you in a hyperthermia machine, when you get this hot, your blood pressure goes up, your heart rate goes up, your cortisol goes up, you're hot. It's a stressor. And yet there's something about that stressor that produces, it sets in motion some sort of compensatory reaction that then makes people feel a lot better.

And in fact, we increasingly think in terms of the IL-6, that what it is, it's not that it's an inflammation thing that's good for you, it's that IL-6 is inflammatory, but all systems in the body have sort of counter, they have checks and breaks. IL-6 turns on a lot of anti-inflammatory pathways also. And we have some evidence that what's actually going on with hyperthermia is that it's turning on this IL-6, and that's setting in motion afterwards a strong anti-inflammatory response. So it's interesting, we really are beginning to understand that heat, it's not just hoodoo voodoo, and it's not just that it makes you feel good, it's that it activates systems in the body that affect the brain and that makes you feel good. And if you're depressed, seems to hold real promise as an antidepressant strategy.

Charles Raison, MD, is a Mary Sue and Mike Shannon Chair for Healthy Minds and a Professor in the Department of Psychiatry at the University of Wisconsin – Madison. Dr Raison received his medical degree from Washington University in St Louis, Missouri, where he was elected to Alpha Omega Alpha and won the Missouri State Medical Association Award. He completed residency training at the UCLA Neuropsychiatric Institute and Hospital in Los Angeles. In addition to his medical training, Dr Raison obtained his Masters of English from the University of Denver.