Is There A Link Between Inflammation And Depression?

The World Health Organization estimates that 5% of adults in the world suffer from depression. Along with depressive moods and lack of motivation, depression can also manifest as pain or fatigue in the body, especially in some cultures. Depression can also accompany chronic diseases such as cardiovascular disease, cancer, and diabetes.

Chronic disease is also associated with chronic inflammation, which is when your immune system continually sends out inflammatory cells and cytokines. Cytokines are proteins that signal when to send more immune cells to help fight any threats to your system. Chronic inflammation can cause pain in your joints, chest, or abdomen, as well as fatigue, among other symptoms.

Because depression can be linked to chronic disease, and chronic disease is linked to inflammation, researchers became interested in a possible link between inflammation and depression. Does inflammation cause depression, or does depression cause inflammation? It's a little complicated, so let's take a look at some of the research to help explain.

Depression and body inflammation

A 2020 study in Neuron said that psychological distress produces an inflammatory response. In some people who are depressed, the immune system may have a difficult time regulating itself, which could mean excess inflammation.

But not all people who are depressed have inflammation — and different types of inflammation may be connected to different types of depression. Certain inflammation responses might resist antidepressants, which could be one of the reasons some people with major depression don't get relief from the available antidepressant medications. 

Although our immune system tends to weaken as we age, causing more inflammation, it doesn't necessarily lead to depression, according to a 2022 study in Nature Translational Psychiatry. The study recruited 63 people between the ages of 50 and 80 who had major depressive disorder and didn't have an inflammatory-related disease. The researchers compared their inflammation levels with 24 healthy people and found no differences in inflammation.

The researchers concluded that depression in older adults isn't necessarily related to inflammation unless they already have an inflammation-related illness, such as arthritis. In other words, chronic disease that causes inflammation might also contribute to depression, but an older adult with depression doesn't necessarily have issues related to inflammation.

If you or someone you know needs help with mental health, please contact the Crisis Text Line by texting HOME to 741741, call the National Alliance on Mental Illness helpline at 1-800-950-NAMI (6264), or visit the National Institute of Mental Health website.

Depression and brain inflammation

Even if people with depression don't have inflammation in the body, inflammation could occur in the brain. A 2015 article in JAMA Psychiatry did PET scans on 20 people with major depression compared with 20 healthy controls. The people with major depression had significantly more neuroinflammation — or inflammation of the brain — than the healthy people.

Depression is often characterized by sadness or emptiness, but lack of motivation is another symptom of depression. The American Psychological Association found a link between inflammation and depression when they noticed how interferon-alpha to treat chronic hepatitis C caused depression in about 30% of the patients.

Because the interferon-alpha caused people's immune systems to kick into high gear, it signaled for other parts of the body to use less energy, such as producing dopamine. This may have caused people to become less motivated.

To address inflammation in the brain's reward systems, a 2022 study in Molecular Psychiatry recruited people with depression who weren't taking medication but had different levels of inflammation. The people were given levodopa to reverse the effects of brain inflammation and increase dopamine levels in their brains. Those with higher levels of brain inflammation had improved their motivation and other depression symptoms.

Therefore, inflammation may contribute to some cases of depression, but not others. Whether or not a person has chronic inflammation may play a role in which treatments are most effective.