The link between inflammation and depression | Charles Raison
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More and more scientists are discovering that the brain and the immune system are intricately connected. Inflammatory markers, such as cytokines, are elevated in people with depression. Investigators observed that a subset of patients treated for hepatitis C using repeated doses of interferon-alpha, which stimulates inflammation, developed depression. In this clip, Dr. Charles Raison describes the convergence of data that is directing scientists to uncover the connection that exists between inflammation and depression.
- Charles: You know, when people began to realize back in the 80s that there was this link between the brain and the immune system that was more profound than we originally thought, right, I mean, originally, people thought the immune system was down to dealing with infection and the brain was about behavior. Now, of course, we know that they’re really one system. People thought about it in terms of immune suppression, you know. I mean, I think so many things were lost from the lives of people with depression that have sort of made thematic sense to think that your immune functioning might be lost too. So it was really quite a shock in the 90s when assays got better, and we begin to realize that if you measured inflammatory markers, so these are chemicals like cytokines that get kicked up when you get the flu or something like that. Then when you looked at those sort of chemicals, they were actually elevated in depressed people. This was shown sort of again and again. And then we began to realize that if you were exposed to these chemicals, you were likely to get depressed. So some of the research that we did, and many other people did, beginning about 2000 was with drugs like interferon. So there’s a thing called interferon alpha which was used somewhat in cancer, but a great deal for many years to treat Hepatitis C. It’s a chemical your body makes that basically turns on inflammation. You know, if I were to take you and inject a bunch of interferon alpha into your arm, within an hour you’d be feeling sick. You’d have a fever. You’d feel, you know, crappy, and you’d wanna lay down. It activates all these inflammatory chemicals in your body. Turns out that if people do that to themselves on a repeated basis for something like curing Hepatitis C, a very significant proportion of them become depressed. Many become like really clinically depressed: suicidal, hopeless, helpless.
- Rhonda: At long term?
- Charles: Oh, well, long term while you’re getting the treatment. The interesting thing is that the vast bulk of people recover pretty much completely within a couple weeks of stopping it. So it really is the sort of drug, if you’re constantly exposed to inflammatory stimuli at a high level, you know, people get exhausted, depressed, or sleep gets messed up. Yeah, unfortunately, there are actually a number of data points suggesting that some people do have long term, you know, sort of mood disturbances after a chronic bout of inflammation from interferon. We know it from other studies, sort of population studies, that if you have episodes of inflammation earlier in life, so for instance, if you have an autoimmune condition, or if you have bad infections, you have the kind of infections that land you in the hospital, you’re significantly more likely to subsequently develop significant major depression. But significant schizophrenia and other disorders too. So it looks like there’s something about chronic inflammatory activation that induces changes in the brain and body that tee you up for depression. In fact, we can talk about it. We know a lot about what those changes are. So there was this convergence of data suggesting that, yeah, that inflammation, the sorts of acute, especially acute reactions your body does to dangerous pathogens, that those chemicals induce depression. Now we and others were some of the first suggests that it may in fact, there may be an evolutionary advantage to inflammation inducing depression. We can talk about that, but the fact that those things are linked, is pretty clear.
A test used in laboratory medicine, pharmacology, environmental biology, and molecular biology to determine the content or quality of specific components.
An immune disorder characterized by an immune response to and subsequent destruction of the body’s own tissue. The causes of autoimmune diseases are not known, but a growing body of evidence suggests they may be due to interactions between genetic and environmental factors. Autoimmune diseases affect approximately 7 percent of the population in the United States and are more common in women than in men. Examples include type 1 diabetes, Hashimoto’s thyroiditis, lupus, and multiple sclerosis.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
A group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and tumor cells. Interferons are named for their ability to interfere with viral replication and are critical components of the body's innate immune response to viruses. SARS-CoV-2, the virus that causes COVID-19, impairs the body's interferon response.
In general, anything that can produce disease. Typically, the term is used to describe an infectious agent such as a virus, bacterium, prion, fungus, or other microorganism.
A mental disorder characterized by abnormal social behavior and failure to understand what is real. Common symptoms include false beliefs, unclear or confused thinking, hearing voices that others do not, reduced social engagement and emotional expression, and a lack of motivation. People with schizophrenia often have additional mental health problems such as anxiety disorders, major depressive illness, or substance use disorders.
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- Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF).
- Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014)
- Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010)
- Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013)
- Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021)
