Dr. Charles Raison on the Link Between Inflammation and Response to Psychotherapy

(Part 2 of a 4-part series)

Psych Congress cochair Charles Raison, MD, presented a session on the impact that inflammation has on mental health at the 2020 virtual Psych Congress Elevate conference. In this video, he explains how increased inflammation can affect response to psychotherapy.

Part 1: Health Effects of Chronic Increased Inflammation

Dr. Raison, a leading researcher in the field of immune-brain interactions, is the Mary Sue and Mike Shannon Chair for Healthy Minds, Children & Families; Professor, Human Development and Family Studies, School of Human Ecology; and Professor, Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin- Madison. He is also Director of Clinical and Translational Research for the Usona Institute, which conducts research on the therapeutic effects of psilocybin.

Read the transcript:

There's been a lot of interest in inflammation, not just as a mechanism whereby people become depressed or anxious, but also in terms of whether or not inflammatory biomarkers, so inflammatory chemicals in the body, might predict treatment response.

There's a really interesting literature. The literature that most people are aware of, the thing that's been looked at the most, is whether or not how inflamed a person is predicts how they're going to respond to a psychotropic medication. Interestingly, there's a much smaller data set, but it's fairly consistent, suggesting that inflammation may also affect how people respond to behavioral treatments like psychotherapy.

So there's a couple of studies suggesting that people who are depressed, who have elevated levels of inflammation (and again this is measured just by something like C-reactive protein in the blood) that people that have elevated inflammation do not respond as well to psychotherapy as do people with lower levels of inflammation. Now, this is interesting because one of the things that inflammation seems to do is to make people feel more socially disconnected.

So Naomi Eisenberger and colleagues, for example, at UCLA have done a series of really groundbreaking studies where they took folks that were not depressed, that were medically healthy and they injected with inflammation, so like a time limited dose of inflammation. When they did that, they found that, in general, people began to feel more depressed. They also began to feel more socially isolated, lonelier.

It turned out that the more lonely or isolated people felt, the more depressed they felt. Now interestingly, this effect was really only seen in women, and there are a number of lines of evidence suggesting that women may be more vulnerable to the depressogenic and socially isolating effects of inflammation.

Nobody's ever looked at that in terms of psychotherapy. The prediction would be that the effect of increased inflammation on reducing response to psychotherapy might be especially prominent in women. That would be a really interesting study to do.

There's another line of converging evidence though that supports the idea that inflammation may impede people's ability to access therapeutic benefit from psychotherapy. That comes from what is now really a quite robust literature, suggesting that increased inflammation inhibits the placebo response. So there are now several studies showing, and some of them quite large, by the way, showing that as people with mood disorders have increasing inflammation, they get less and less of a placebo response.

So you think about what is a placebo response? Well, it's kind of mysterious but we know it something to do with the therapeutic alliance, with a sense of expectation, of a hope, of just a number of these factors that in the psychotherapy literature are called common factors. They're factors that seem to underlie the benefit of a wide range of psychotherapeutic interventions. So it makes sense that if those capacities of a person are impaired by inflammation, that people should be less responsive, generally, to something like psychotherapy.

Now this sounds really, really bad, but from an evolutionary perspective, it makes a lot of sense. So what does inflammation do? Well, it activates processes in the body that help you fight off an infection. It also causes change in how you think and feel and act. This is how it can produce depression.

But in the context of risk of infection or in the context of being infected, if your inflammation goes up and that causes you to step away from other people, that can be very protective in terms of surviving an infection or not getting infected in the first place.

I just can't tell you how relevant this is in the age of COVID where we're struggling with this dynamic between the sort of evolved human need for social connection and this evolved human fear of contagion and infection.

So in the context of many aspects of the modern world, if your inflammation's up, that's not very helpful. Your inflammation's up from being obese or being stressed out, and that makes you feel disconnected from other people, that's clearly not helpful. But again, across evolutionary time, the increased inflammation causing these sorts of withdrawal behaviors, it really was probably quite adaptive.