Introduction: The Inflammation Connection

April 30, 2018
Charles Raison, MD

This 2-part Special Report devotes itself to the new inflammatory world that clinicians and researchers find themselves in. Most of our prior and current preconceptions about the role of immunity and mental illness have been-and are-wrong.

Dr. Raisonis 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.

When I attended medical school in the mid-1980s, no one imagined that the immune system had anything to do with the brain. When I became a researcher in 2000, we were convinced that inflammation would only be relevant to patients with medical illnesses that might account for their immune activation. Now, in 2018 I find myself amazed that inflammation is frequently named as the root cause of all psychiatric conditions- the sine qua non of all mental illness.

This 2-part Special Report devotes itself to the new inflammatory world that we-as mental health clinicians and researchers-find ourselves in, and it does an admirable job of showing how most of our prior and current preconceptions about the role of immunity and mental illness have been-and are-wrong.

In retrospect, my years in medical school seem like the dark ages. We now know the immune system and the brain have everything to do with each other: really, they are best understood as part of one larger system with causal influences that move in both directions. Brain states that produce mental illness also tend to activate inflammation. And inflammation is equally capable of producing depression, anxiety, fatigue, and social withdrawal.

It seemed so logical in 2000 that inflammation could only produce mental illness when a person had a good excuse for inflammation, such as an infection or a cancer. We didn’t know then that psychological stress activates inflammation and that this activation would be found to predict the later development of psychopathology.1 Far from being specific to any one mental illness, or a sub-population within a mental illness, inflammation turned out to be a common denominator and likely risk factor for every manner of psychiatric disturbance, from schizophrenia to obsessive compulsive disorder, from mania to depression.2

On the other hand, our hopes that major depression might turn out to be an inflammatory condition that could be uniformly treated with anti-inflammatory medications turned out to be as wrong as all the other assumptions prevalent in the field and in my own brain. It is increasingly clear that inflammation is not the cause of depression: it is at best one cause of depression. We now know, in fact, that depressed patients with elevated depression have different patterns of brain functioning than do patients who are just as depressed but have low levels of inflammation.2 And the story gets trickier, because several studies suggest that further lowering inflammation in these non-inflamed patients makes things worse, not better.

What does it all mean? Fortunately, the articles in this Special Report do an outstanding job of glossing our best current understandings, which are: What are these understandings?

• First, that inflammatory processes induce changes in brain/body functioning that can contribute to the development of a wide range of psychiatric conditions. Inflammation is an equal opportunity risk factor, with specific disease pathogenesis depending on factors such as when in the life cycle the inflammatory event(s) occur and/or genetic predisposition of individuals.

• Second, that a wide range of environmental adversities, many of which-like stress-we don’t tend to think of as immunological, can be proinflammatory and likely increase the risk of mental illness through this mechanism.

• Finally, that even though inflammation may be a cause of a given mental illness in a given individual, psychiatric disorders are not inflammatory conditions. There are plenty of other ways of getting depressed, or manic, or psychotic.

Our recent celebration of all things inflammatory will not allow an escape from the truth-that psychiatric treatment will never be “one size fits all.” How anti-inflammatory strategies will fit into our larger armamentarium is one of the most exciting questions facing the field of psychopharmacology.

Here’s to hoping that when the next Psychiatric Times Special Report on inflammation comes out, we will have the answers.

In this Special Report:

Is PTSD a Systemic Disorder?

Five Things to Know About Inflammation and Depression

Why Are Depressed Patients Inflamed? A New Path to Personalized Treatment in Psychiatry

Where There’s Smoke, There’s Fire

Disclosures:

The author reports that he is a consultant for Novartis, Usona Institute, and Emory Healthcare.

References:

1. Wirtz PH1, von Känel R. Psychological stress, inflammation, and coronary heart disease. Curr Cardiol Rep. 2017;19:111.

2. Miller AH1, Haroon E1, Felger JC1. Therapeutic implications of brain-immune interactions: treatment in translation. Neuropsychopharmacol. 2017;42:334-359.