How Inflammation Can Lead to Depression

New research discusses the effects of chronic stress on the immune system.

Posted Dec 31, 2019 | Reviewed by Lybi Ma

When we think of things like depression, the role of inflammation seems secondary to, perhaps, social circumstances that cause sadness and trauma, or even our genetics, which is a continuous field of study in mental health. Inflammation in brain and spinal cord tissue (also known as headaches and backaches) can usually be lessened by swallowing a Tylenol or two. But researchers in Georgia and South Carolina were recently awarded grants from the National Institute of Mental Health (NIMH) to study the biochemistry that contributes to inflammation.

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"Everything has a price. The price, however, isn't always money." -Ahmed Mostafa
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It goes back to swallowing a Tylenol to make your pain dissipate—in other words, your biochemistry. In order to better understand our biochemistry and why Tylenol and other drugs are effective, we have to understand something called the complement system or the complement cascade. The complement system is part of a human’s immune system.

Our immune system provides checks and balances throughout the body to keep us healthy. The complement system is made up of proteins derived from the liver. If your liver isn’t healthy, there’s a good chance you may be unhealthy in other areas as well—including your mental health.

The complement system was named by Paul Ehrlich (1854-1915). Ehrlich won a Nobel Prize for his contributions in immunology; he discovered the cure for syphilis, and in so doing, coined the term “chemotherapy.” Chemotherapy basically means using chemistry to treat disease—though today, people use the phrase almost exclusively for the treatment of cancer.  

When a human gets an infection—which can include something like the common cold or flu—one of the first responses by the immune system is inflammation. Inflammation is a physical barrier, meant to help contain the infection in order to help promote healing. But researchers at the Medical College of Georgia at Augusta University have found that chronic stress actually causes inflammation in the brain in the same way that cold germs cause inflammation in our throat and nasal passages. Inflammation of the brain essentially destroys the connections between neurons, causing depression.

Monocytes are white blood cells. Monocytes circulate throughout our bodies during periods of stress as a line of defense. But it is the microglia or the immune cells in the brain that may be delivering excess C3, a small protein from the complement system that causes continuous inflammation in the brain, which then contributes to depression.

Researchers at the Medical University of South Carolina College of Medicine are collaborating with Georgia researchers because their lab synthesizes something called “complement inhibitors,” or drugs that block C3 activation.

Though interferon-alpha is a drug used to treat cancer, it’s also a naturally-occurring protein produced by our bodies to stimulate the immune system in order to stop viral infections and the development of melanoma (skin cancer)—a very useful aspect to our biochemistry. The problem comes in with prolonged use of the synthesized version. Patients treated with interferon-alpha for long periods of time had depression and other mental health issues.[i] It’s interesting to note that when overused as a synthesized drug, the very protein our bodies create on their own works against us.

The theory is that increases in interferon-alpha—whether through chronic stress or something like the treatment of cancer—activate the microglia, the immune cells in the brain. Activating the microglia ups the production of the C3 protein, which in turn not only damages communication between our neurons but outright destroys the connections between them. When our neurons can’t communicate, we don’t think properly. When we can’t think properly, we can’t act properly.

As we move into 2020, it’s important to remember that keeping ourselves in stressful environments—whether at home or through a job—is not just causing situational depression (or temporary depression that goes away when the difficulty does), it may actually be destroying brain function. The more we understand about how our bodies work, the healthier our minds will be, too.

In the new year, it’s of the utmost importance to remove yourself from any relationship that is causing chronic stress. Think of people who abuse you as not just abusers you can walk away from, but individuals who are causing you, your body, and your mind irreparable harm that can and will permanently affect both your physical and mental health.

No person or situation is worth injuring your life. Start fresh in 2020. If you have a difficult relationship, begin regular counseling sessions so you can at least have less stress as you work toward financial independence, increasing your ability to leave the toxicity behind. If your partner isn’t amenable to counseling, you can always go to talk therapy sessions on your own.

Protecting your brain from the effects of chronic stress protects every aspect of your life. The year 2020 is all about living longer and stronger. That starts the moment you begin believing in yourself.


i] Medical College of Georgia at Augusta University (21 Nov 2019). Dissecting connections between chronic stress, inflammation and depression. Science Daily. Accessed 31 Dec 2019. <>