Generalized Anxiety Disorder Linked With Inflammation, Unbalanced Immune System

New evidence indicates that Generalized Anxiety Disorder (GAD) is associated with an imbalance of substances involved in inflammatory and anti-inflammatory responses. GAD is classified as a mental disorder in the Diagnostic and Statistical Manual of Mental Disorders. It is characterized by uncontrollable, excessive, and sometimes irrational worry about normal events or activities. People suffering from GAD live in a perpetual state of worry. The condition is far from rare. Nearly seven million adults in the United States are affected by Generalized Anxiety Disorder.

As it turns out, there may be a very physiological reason for GAD. Only further research will prove or disprove speculation, but Generalized Anxiety Disorder may be another condition that is symptomatic of an unbalanced immune system.

Symptoms of Generalized Anxiety Disorder include constant worry, restlessness, and difficulty concentrating. It is now linked to inflammation. [Image by Antonio Guillem/Shutterstock]

Among people with GAD, researchers found immune systems out of balance.

Researchers involved with this groundbreaking study published in Brain, Behavior, and Immunity, looked at the cytokine profiles of patients suffering from Generalized Anxiety Disorder. Cytokines are secreted by the immune system and are involved in both promoting inflammation and decreasing inflammation. The cytokine profiles that were examined included levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10.

This breakthrough research could be important for millions of anxiety sufferers.

According to Brain Immune, one of the few platforms that reported on this research, IFN-γ is needed to activate the immune system against pathogens and to fight against tumors. TNF-α causes the inflammation our bodies use to fight acute phases of disease and sickness. Both of these also stimulate the production of inflammatory mediators that are behind chronic, delayed inflammation. The third substance that was examined in patients with Generalized Anxiety Disorder, called IL-10, fights inflammation, reduces the initial acute illness-fighting cells and increases the production of antibodies. As our bodies are engaged in fighting an illness, IL-10 limits the other immune responses, so that our immune systems don’t accidentally attack and damages themselves.

People with Generalized Anxiety Disorder had high ratios of the first two substances mentioned above. Meanwhile, they had low IL-10 serum levels compared to healthy controls. The findings remained even after adjusting for some factors including adjusting for comorbid depression!

“Case-control logistic regression analyses revealed significant differences in serum levels of IL-10, TNF-α, and IFN-γ between GAD and control groups after adjusting for age, gender, body mass index, smoking and alcohol consumption: these group differences were independent of the presence or degree of depression. Comparison of pro-inflammatory to anti-inflammatory cytokine ratios indicated that there were significantly higher ratios of TNF-α/IL10, TNF-α/IL4, IFN-γ/IL10, and IFN-γ/IL4 in the GAD group compared to the control group.”

Could Generalized Anxiety Disorder be the result of a disproportionately low amount of IL-10 compared to IFN-γ and TNF-α? Could Generalized Anxiety Disorder be another example of chronic inflammation?

“This study is the first to investigate both pro- and anti-inflammatory cytokines and their balance in patients with GAD in comparison to healthy controls. The findings indicate a relatively increased pro-inflammatory response and decreased anti-inflammatory response and provide the first demonstration of an altered cytokine balance in GAD. Serum cytokine levels in GAD were independent of the presence of depression.”

Generalized Anxiety Disorder associated with inflammation for first time.
Is Generalized Anxiety Disorder another situation of chronic inflammation? [Image by One Photo/Shutterstock]

The researchers also suggested that they might have an enzyme related to the pro-inflammatory state seen in Generalized Anxiety Disorder sufferers. They say that the activity of a particular enzyme may be altered. They suggested that the enzyme is involved in metabolizing tryptophan. The suggest that the altered activity of this enzyme eventually leads to the degradation of serotonin through a mechanism that is similar to the mechanism seen in major depression.

There is still much research to be done on the topic. In the future, the researchers may look for the cellular source of the cytokines and if there are others at play in Generalized Anxiety Disorder. They also hope to learn the mechanisms the cytokines employ to act as a go-between between the central nervous system and the immune system. Further research will likely be the basis for new therapeutic approaches for treating anxiety.

Dr. Ruihua Hou, lead investigator on the breakthrough research, said in a presentation that greater understanding of cytokines in Generalized Anxiety Disorder would help explain the “unique inflammatory signature” which will help with diagnosis, treatment, and the creation of new drugs that selectively target the specific immune phenotypes of the condition.

[Featured Image by Wavebreakmedia/Shutterstock]