Flu Vaccine in the Body, Flu in the Mind

By Shelby Knowles
Population Health Scholar
University of Texas System
PhD Student in Journalism
UT Austin Moody College of Communication

Dr. Marisa Toups is a psychiatrist at UT Austin Dell Medical School, specializing in the study of the interplay between physical and mental functions in health and disease. Her work focuses on understanding the effects of medical illness, particularly chronic inflammatory disorders, on mood and function. She also has extensive experience conducting clinical trials to develop new ways of assessing and treating depression.

Texas Health Journal spoke to Toups about her recent work on the effects of the flu vaccine on people experiencing depression, the effects of depression on how the body reacts to the vaccine, and the importance of getting the flu vaccine. 

Will you tell us more about your work on the connection between depression and the seasonal flu vaccine?

We’re working to learn more about how people with depression respond to having their immune system activated by a stimulus, like the flu vaccine. In some sense, the research isn’t specifically related to influenza, but we chose that model because every year people everywhere get the flu vaccine.

The vaccine is composed of part of the flu virus – proteins – that are recognized by what we call the “innate” immune system. “Innate” means that even if your body has never been exposed to a virus before, the immune system can recognize that it’s “bad.” The immune cells that first find the proteins signal to other immune cells to mount a defense, and we call this signal “inflammation.” A simple way of putting it is that inflammation is the initial or activating phase of the immune response; it normally goes away as the immune response matures or resolves. The brain detects the inflammatory signal and can produce what we call “sickness behavior” – you feel and act sick. So after people get the flu shot, sometimes they feel like they “have the flu.” (Of course, actually having the flu, particularly for people with depression, is much worse. Then you'll have sickness behaviors along with the actual sickness, and the effects that the sickness is likely to have on mood.)

I should point out how much depression resembles being sick. Both involve being tired, sleeping poorly, not wanting to be social or do other things we usually find fun, and having cognitive trouble. This makes us wonder whether sickness and depression may be related. So we did a study to see whether people with depression are more likely to feel bad after they get their flu shot, and we found that they do.

I saw that right up at the top of your paper. You write: “When experiencing immune system activation, individuals exhibit a collection of normal ‘sickness behaviors’ including lethargy, sleep disruption, anhedonia, loss of appetite, social isolation, and cognitive difficulties Sickness is an adaptive response to infection, redirecting energy allocation to rest and allowing healing as well as preventing the spread of disease to others by limiting social contact.”

I can see why this would make sense with the flu. Your body sends a signal that you should feel tired, so that you rest and are able to recuperate (and also stay away from other people you could infect). Are you saying the flu vaccine can produce the same signals from the brain, even though we’re not actually sick?

I think in some cases, yes.

We might call sickness behavior a “meta-cognition,” meaning something you don't consciously decide, but your whole body sort of decides for you.

The idea is that people with depression may have faulty meta-cognition. The brain isn’t able to accurately tell whether or not the body is healthy, so they come to believe that something is or could be “wrong with them” all the time.

The flu vaccine gives us an opportunity to test this directly. If your metacognition is “correct,” the flu vaccine triggers very mild or no sickness behaviors, but in our study we saw that in depression there is a bigger sickness response. We plan to follow up with another study in which we will directly measure inflammatory markers after vaccination to see if those are also higher in depression, and whether depressed people make as many antibodies to the flu virus as healthy people do.

How did you become interested in this connection?

I originally got into it because I wanted to know if we could prove that depression is related to sickness behavior, and looking at vaccine-stimulated inflammation is a safe way to do that. But the more we learned about influenza and depression, the more curious we became. The fact that depressed people feel worse after vaccination may indicate that their immune system is responding to the vaccine in a less effective way compared to people who feel well. That may then lead to inefficient production of antibodies and less protection from the vaccine.

We know already that people with depression are more vulnerable to getting the flu, so I partnered with Jenny Jiang, Assistant Professor in Biomedical Engineering here at UT, whose research focuses on systems immunology. She is very interested in why some people are less protected than others by the flu vaccine. The idea was that we will look to see if people with and without depression respond to the vaccine differently. And, if there are different responses, is it related to the ability to develop antibodies against influenza?

Another research group recently published the finding that people who were in a better mood the day they received their vaccine made more antibodies. Although they didn’t ask about depression specifically, this finding encouraged us to look further.

You write about the connection between the flu vaccine, depression and aging. Can you expand on that?

In general, the largest identified factor that causes people to have a poor response to the influenza vaccine is age. Elderly people don’t make as many antibodies as younger adults. It seems that as we age, our immune system also ages and doesn't work as effectively.

One hypothesis is that people with depression have immune systems that age at a faster rate than healthy people, so they're responding as if they're older. In some ways, depression may represent an accelerated aging process; people with depression are more likely to develop diseases of aging, including heart disease, Alzheimer's disease, and cancer.

What are the clinical or public health implications of this research?

The clinical implications of the relationship are huge, because the lifetime prevalence of depression is close to 20 percent in the US. People with depression have a bigger medical health risks, and it puts a huge burden of illness on society.

What are some misconceptions about your research?

I worry that people may see this as a reason to skip the flu shot. Everybody should still get it!  There's a lot of controversy about vaccines right now, so here was some concern about doing research which might show vaccines in a bad light, but I feel strongly that we have to understand how things work to make them better. I think a lot of times, when people come in saying, “I really feel the flu vaccine gives me the flu,” physicians have dismissed that subjective experience. Instead, we should acknowledge that it happens, and figure out how to manage it so we can encourage people to go ahead and get vaccinated.