Summary: New evidence suggests a strong link between infections and mental illness. The body’s own inflammation drives much of it. Infections like sepsis and pelvic inflammatory disease can leave lasting mental health problems, like anxiety and depression. These can stay even after the infection is gone. Long infections and inflammation that will not shut off sit at the center of these problems.
Mental illnesses are hard to diagnose, and their causes are still poorly understood. That is because they build slowly over years. They likely come from a mix of things, like stress, genes, and even inflammation. There are also no reliable lab tests to confirm them. Doctors mostly diagnose them by talking with and watching the patient.
Still, science is learning more about what causes mental illness. Now a new study suggests inflammation may play a bigger role than we thought.
One of these new studies, published in the World Journal of Psychiatry, looked at the link between inflammation and a higher risk of mental illness.
New evidence suggests a strong link between infections and mental health problems. It shows that infections spread through the body can cause mental symptoms, even when the brain itself is not infected.
The COVID-19 pandemic was a clear example. Mental health problems such as anxiety, depression, and trouble thinking rose noticeably in people who were infected. These problems often lasted long after the infection was gone. That shows the body’s inflammation plays a key role in driving them.
Sepsis is an infection that spreads through the whole body. It often causes sepsis-associated encephalopathy (SAE). SAE is brain dysfunction that shows up in up to 70% of patients.
SAE causes brain symptoms like confusion, trouble thinking, and coma. It comes not just from the infection itself but from the body’s long inflammatory response. That inflammation can settle into a steady, low-grade burn. Then mental health problems follow. So these problems are likely tied to the body’s inflammation, not the infection itself.
Pelvic inflammatory disease (PID) is another infection that can affect the whole body. It can even cause mental symptoms.
PID is often caused by sexually transmitted infections. It can lead to serious problems such as tubo-ovarian abscess (TOA), chronic pain, and infertility. PID that drags on can kill cells through pyroptosis. Pyroptosis is a built-in form of cell death switched on by inflammasomes, the cell’s inflammation alarms. This makes PID’s physical symptoms worse. It may also trigger mental health problems in ways like those seen in body-wide infections such as sepsis.
Long infections have been shown to hurt mental health for years. Infections such as brucellosis and HIV are tied to lasting inflammation and an off-balance immune system. That can inflame the brain and lead to mental symptoms.
For instance, in mice, brucellosis infection lowered drive, raised anxiety, and changed brain chemistry. Dopamine and serotonin dropped in key brain areas such as the hippocampus and frontal cortex. These findings show how much long-lasting infections can hurt mental health. They feed conditions like depression and anxiety, which are often hard to treat and manage and call for interventional pain management.
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Researchers are also looking at the hypothalamus-pituitary-adrenal (HPA) axis. This is the body’s stress system. It matters during infections. Infections switch on the HPA axis. It releases cortisol and other stress hormones (catecholamines). These are vital for handling short-term stress.
But when the HPA axis stays switched on, the body can stop responding to cortisol. This is called glucocorticoid resistance. It feeds chronic inflammation and mental illness. High levels of inflammation signals (cytokines) such as IL-1β, TNF-α, and IL-6 make it worse. They play a role in major depressive disorder (MDD) and other mental illnesses.
Inflammation during infections also changes metabolism in ways that seem to affect mental health. Inflammation signals change how the body uses tryptophan, the building block of serotonin. So less serotonin gets made. More kynurenine gets made instead. Kynurenine has been tied to brain inflammation and trouble thinking.
These changes help cause sickness behavior. Its signs include fatigue, pulling away from people, and anhedonia (loss of pleasure). These signs are common in both body-wide infections and mental illness.
Inflammation that will not shut off stands out as a key cause of mental illness after infections. It can come from long infections, immune problems, or stress.
Long infections are a big public health problem. The harm is not only from the infections themselves. It is also from the long-term mental health problems they can cause. These can hit people’s jobs and finances hard, especially in places with a lot of long-lasting infectious disease.
Infections that cause long-term inflammation have also been tied to organ damage, or to making old damage worse. For example, after COVID-19, some patients get damage to the pancreas. That leads to high blood sugar and steady, low-grade inflammation.
Similar problems show up in people recovering from sepsis. Their immune system can stay weak and inflamed for a long time, because of changes in T cells and in how the body makes blood cells. They can also have problems from damage to vital organs such as the kidneys and heart.
Evidence suggests that antibodies made during infections can trigger brain and mental health problems through cross-reaction. The antibodies mistake the body’s own tissue for the germ. For example, strep infections can trigger brain and mental symptoms. COVID-19 can cause antibodies against cortisol. Both may lead to chronic inflammation and brain and mental health problems. Getting timely help from a chronic pain specialist helps treat these problems at the root.
Frequently asked questions
Can inflammation cause depression and anxiety?
Yes. This research ties mental health problems more to the body’s inflammation than to the germ itself. Inflammation signals such as IL-1β, TNF-α and IL-6 play a role in major depressive disorder. They play a role in other mental illnesses too. After COVID-19, anxiety, depression and thinking problems rose in people who were infected. Those problems often lasted long after the infection was gone.
Can anxiety or depression last after an infection is gone?
Yes. Sepsis and pelvic inflammatory disease can leave anxiety and depression behind. This can happen even after the infection clears. Sepsis often causes sepsis-associated encephalopathy, seen in up to 70% of patients. The long inflammatory response that follows can settle into a steady, low-grade burn. Long infections such as brucellosis and HIV are tied to lasting inflammation. They throw the immune system off. That can inflame the brain and cause mental symptoms.
How does inflammation lower serotonin?
Inflammation signals change how the body uses tryptophan, the building block of serotonin. Less tryptophan becomes serotonin. More becomes kynurenine, a compound tied to brain inflammation and trouble thinking. These shifts help explain sickness behavior. That means fatigue, pulling away from people and anhedonia, the loss of pleasure. The same symptoms show up in body-wide infections and in mental illness.
How does stress affect inflammation?
Infections switch on the hypothalamus-pituitary-adrenal (HPA) axis, the body’s stress system. It releases cortisol and other stress hormones. That response is vital for handling short-term stress. When the HPA axis stays switched on, the body’s response to cortisol weakens. This is called glucocorticoid resistance. It feeds chronic inflammation and mental illness. Inflammation signals make the response worse.
Source:
Ferat-Osorio, E., Maldonado-García, J. L., & Pavón, L. (2024). How inflammation influences psychiatric disease. World Journal of Psychiatry, 14(3), 342–349. https://doi.org/10.5498/wjp.v14.i3.342
Dr. Gurpreet Singh Padda, MD, MBA, MHP
