The Relationship Between Inflammation and Mental Illnesses

(Part 3 of a 4-part series)

In this video, Psych Congress 2020 cochair Charles Raison, MD, discusses the relationship between inflammation and mental illnesses, and misconceptions about the connection between the two. Dr. Raison, a leading researcher in the field of immune-brain interactions, will speak at Psych Congress 2020 on the role of inflammation in mental health. 

Part 1: Health Effects of Chronic Increased Inflammation

Part 2: The Link Between Inflammation and Response to Psychotherapy 

Dr. Raison 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 video transcript:

The most common misunderstanding about the link between inflammation and mental health is that somehow inflammation is an explanation for mental illnesses in general, or said differently, that mental illnesses are inflammatory disorders.

I've been working in this space for a number of years, and when we first started out, we were really excited. There began to be all these data suggesting that if you looked at groups of depressed people or folks with schizophrenia or folks with autism or bipolar disorder, that as a group, people with these psychiatric conditions had increased inflammation compared to healthy controls. Not sky-high inflammation, but elevated inflammation.

We and others had done studies showing that if you injected people with inflammation, using one model or another, that they had a high rate of becoming depressed. It really looked like maybe psychiatric conditions could be reconceptualized as being immune conditions, or inflammatory conditions.

What data over the last 10 years have shown is that this is clearly not the case. Mental illnesses—things like depression, schizophrenia—are not inflammatory disorders. You can be very, very depressed or very, very psychotic and have very, very low levels of inflammation.

In fact, most people, in most studies, that have a psychiatric condition have levels of inflammation that are indistinguishable from folks that don't have those conditions.

The reason that the mental illnesses are associated with increased inflammation is because there's a subgroup, there's a portion of people with these illnesses that have clearly higher levels of inflammation than is average for folks without them.

This and other studies have shown that, right now, our best conceptualization is really this: that there are a subset of individuals with psychiatric conditions—the one that's been best characterized is major depression, so let's just take that condition. There's a subset of individuals with major depression who have elevated inflammation, and those people seem to respond differently to treatment, to pharmacologic treatment than depressed people with lower inflammation.

My old friend and colleague, Andy Miller, at Emory [University] has shown that they also have different patterns of brain connection. He, in a series of really impressive studies, has shown that people that are equally depressed—but one group has elevated inflammation, the other group doesn't—the folks with elevated depression have differences in key parts of their brain in what's called the ventral striatum, which is an important area for pleasure and for reward motivation, and changes in how that area is connected with the medial prefrontal cortex, which is important for guiding our decision-making and having a sense of what we're doing in life.

Now, the way to think about it is that inflammation can cause depression, and because of that, there are a subset of folks that have probably come by their depression, and perhaps to some degree other mental illnesses, by having increased inflammation.

Those people probably have a different biology in some important ways than people that are just as impaired with a psychiatric condition but have lower levels of inflammation. One of the implications of this is depression, other psychiatric conditions, are not inflammatory disorders.

The best studies we have to date suggest, therefore, that just trying to lower inflammation willy-nilly across groups of people with a psychiatric disorder is not an effective treatment strategy. In fact, for some people with these conditions, it can actually be worse than using a placebo.