Why you may feel depressed and anxious when you’re ill – and how to cope with it

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Winter illnesses are all around us at the moment – from the common cold, COVID-19 and flu to strep throat and stomach bugs. All have one thing in common: they can make you feel miserable. These illnesses often come with fatigue, lack of appetite and concentration difficulties. Sufferers often just want to be left alone many people even experience sadness and anxiety.

Researchers have uncovered why that is. When your body is under attack by a pathogen, some of your immune cells recognise the pathogen and take action to eliminate the threat. To be successful, they need to rally other immune cells as well as several organs of your body.

To do so, they secrete specific proteins, called cytokines. These are messengers, communicating the presence of a pathogen throughout your body, including to your brain.

Once the cytokine signal reaches your brain, it triggers changes in the activity of many brain structures. This leads to the development of fever, but not only that.

These brain changes also lead you to feel and act differently: you are much less motivated to do things you usually like and would rather be alone and in bed. Ultimately, you feel fatigued and you lack appetite. But you can also be more sensitive to negative stimuli, which can easily make you sad and anxious.

The feelings of sickness are triggered by your immune system.
Credit: Julie Lasselin; sick person: brgfx/Freepik, CC BY-SA

That means that the psychological experience of sickness is not just triggered by your brain or the pathogen itself – it seems to be unleashed by your own immune system.

Making people sick for one day

How can we make sure that the feelings of sickness are really triggered by our own immune system, and not the pathogen? Researchers have actually shown that such feelings can be brought about without a true pathogen being present.

My research group, and a few others in the world, purposely activate the natural immune defences of healthy and young volunteers, without using a pathogen. In several of our experiments, we injected more than 100 study participants with a small dose of lipopolysaccharide, a component of the membrane of the bacteria Escherichia Coli. Because immune cells recognise this component as a pathogenic threat (although no real bacteria are actually present), they get activated and produce cytokines.

As during a real infection, but without the presence of a pathogen, the cytokine signal reaches the brain and triggers behavioural changes together with the feelings of sickness (collectively called “sickness behaviour”).

Interestingly, our participants reported the same symptoms – malaise, fatigue and body pain – without fighting an infection. In the photos below, you can actually see that they look less well after the injection.

Photos of faces of 3 men and 3 women, one surrounded by blue (control) and one surrounded by orange (injectieon).

Participants photographed both after taking saline, a control substance (blue, left side), and after receiving a lipopolysaccharide injection (orange, right side).
Credit: Julie Lasselin

The participants said they would rather be at home than in our study room, and were no longer interested in performing the various tasks we asked them to do. And although they were not specifically anxious or sad before the injection, several of the participants reported feeling anxious and morose afterwards.

Because there were no real bacteria in the blood, and because the liver and immune cells rapidly clear bacterial components from the blood, the production of cytokines lasted only a few hours, typically five to eight hours. And the sickness feelings, including the strong negative emotions that were triggered only a few hours earlier, also subsided within this time frame.

Why do we feel miserable during infections?

The question now is: must we feel sick during an infection? And if so, why? Well, even if you are not fully aware of it, fighting a pathogen requires an incredible amount of energy. Both the activity of your immune cells and the increase in body temperature take a heavy toll. The only way your body can cope with these high energy demands is by strongly reducing the activity of organs that are not immediately needed.

Sickness feelings ultimately ensure that your body energy is not used for activities that are not essential at the time of an infection – you need to be calm and stay at home. Thus, they help you avoid using your muscles and even your brain – making you skip the gym or extensive studying. And feeling sad and anxious prevents you from wanting to go out and party with your friends.

The feelings of sickness are therefore likely to be beneficial in the fight against the pathogen.

This is probably the reason why all vertebrates, and even invertebrates such as bees and ants, behave like we do during infections.

So, it is likely to be difficult to simply think your way out of feeling down when ill. But I hope that this insight will help you take the edge off negative thoughts when confronted with a winter illness. Do not feel guilty or worried about feeling miserable – it’s only natural.

A healthy way to respond might actually to embrace these feelings as a normal response of your body when it needs to fight off pathogens. If you don’t, the chances are you will go on a spiral of guilt, fear and negative emotions that keeps getting worse.

And by the way, if you feel miserable in the days following a vaccination… Don’t worry – it similarly means your immune system is at work.



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