Vaccinating Against Anxiety and Depression
By: Simon Spichak
Tags: Stress, Innovation, Mental Health, Medicine, Science

Vaccinating Against Anxiety and Depression

Microbes in the dirt might lead to an innovative approach to reduce the burden of mental health.

Photo by CDC on Unsplash

I am fascinated by the intersection of mental health and neuroscience. It inspired me to pursue my graduate degree, studying the interactions between the bacteria in our guts and the brain. While we don’t fully understand how these microbes impact the brain, they might provide a new source of treatment for many common disorders. The absurdity and incredulity of a bunch of microscopic organisms aren’t lost on me. I want to share one of the coolest findings in recent years, centered on one such bacteria, found in soil.

Depression is the world’s leading cause of disability, affecting over 250 million people every single year. People might experience prolonged sadness, fatigue, and apathy. Additionally, people with depression often also experience severe anxiety. Anxiety can cause our heart to pace while our mind thinks about impending danger or doom. Many people experience these debilitating symptoms in social settings. During particularly-stressful times, like global pandemics, people become even more susceptible to these disorders.

How do we solve this problem?

We still don’t fully understand what causes depression or anxiety or even how most medications work. In contrast, it is easier to identify what goes wrong during bacterial or viral infection. There’s a tangible target microbial cause that we can train our immune system to handle. By providing a part of a pathogen or an inactivated pathogen, our immune system learns to recognize and mount an effective response against it. The next time we might encounter this pathogen, our body can easily handle it. These strategies allowed humanity to fight diseases like polio and eliminate others like the Black Plague.

Interestingly, a lot of intriguing research finds an overactive immune system in depression, anxiety and a whole host of other brain disorders. A lot of evidence also suggests changes in the composition and function of the gut microbial community in individuals with these disorders. An intriguing question arises: could we vaccinate against anxiety and depression?

Towards a Vaccine for Anxiety and Depression

In recent decades, we have seen vast increases in allergies and other immune-related diseases. In peanut allergies, our immune system overreacts to something harmless. In more severe inflammatory disorders, the body attacks itself, mistaking it for a pathogen. The Hygiene Hypothesis explains some of these increases.

As our day-to-day lives became more industrialized and clean, we are exposed to microbial organisms much less often. Our immune system does not receive sufficient training early in life. When exposed to the mud and dirt of the outdoors, our bodies encounter substantially more bacteria and pathogens. Our immune system needs to learn to categorize different bacteria and pathogens to determine which are dangerous. Then it has to learn how to deal with these situations appropriately. Non-pathogenic bacteria or potential allergens do not need to be attacked by the immune system. Additionally, the immune system learns how to react to a particular threat without causing more harm to the host. Rates of allergies and immune disorders are substantially lower in less industrialized parts of the world due to this effect.

Could these effects also predispose us to increased rates of anxiety and depression?

Photo by Adrian Lange on Unsplash

Christopher Lowry, an Associate Professor of Integrative Physiology at the University of Colorado Boulder, is at the forefront of this exciting research. Using a strain of common soil bacteria, Mycobacterium vaccae, his research team reduces the impacts of stress in rodents. This strain of bacteria was isolated decades earlier in Uganda. Curiously, it boosted the effectiveness of the leprosy vaccine. This uncanny soil microbe showed incredible immune-modulating activity!

In 2004, an oncologist decided to see the impact of this strain on cancer. This U.K. study enrolled patients with inoperable lung cancer who would receive chemotherapy. While it didn’t improve cancer-related outcomes or impact mortality, it showed promise in impacting the mental health of patients. In addition to a higher quality of life, patients receiving the bacteria also experienced fewer side effects of the chemotherapy itself and higher cognitive functioning. Though this trial did not control for the placebo effect, its results caught the eye of Christopher Lowry.

Unlike humans, rodents cannot tell researchers that they are experiencing anxiety or depression. Elaborate behavioural tests were developed specifically to assess anxiety-like and depressive-like responses in rodents. While they aren’t perfect, they’ve allowed researchers to develop anti-depressant and anti-anxiety medication. Additionally, Lowry could look into the rodent brain to try and figure out exactly what’s going on.

In 2007 he published his first study using this bacteria. Administering it to mice, his team found that the immune response activated specific neurons in the brain. This increased the amount of a neurotransmitter involved in regulating mood, called serotonin, in the prefrontal cortex of the mouse brain. This also reduced some anxiety-like behaviors in the mice 12 hours after being given this bacteria.

In 2016, he showed how these bacteria promoted stress resilience across many different behavioural tests. The tests were conducted 1–2 weeks after immunization, showing that there was some sustained effect on stress responses in mice. They also determined that these effects required immune cells that regulated inflammation. More recently, his group is studying how these bacteria could reduce the severity of neurodegenerative disorders in mice.

Vaccinating Neuro-Inflammation

While M. vaccae boosts our regulatory immune response to certain pathogens, it is uncertain if these mouse studies translate to humans. Nonetheless, it could prove valuable in future clinical trials. We already know it’s safe when administered to humans but there are no currently registered clinical trials attempting to test its properties for treating anxiety or depression.

A 2019 study from Lowry’s group identified a specific triglyceride molecule, derived from M. vaccae that interacts with mouse immune cells. Even the molecule alone without the bacteria could theoretically exert some of these immune-modulating effects. Perhaps a way forward would involve screening for immune activation in humans, and using these specific bacterial components to inoculate them against future stress, depression or anxiety.

Lowry predicts that this might become a reality in 10 to 15 years. Perhaps a few decades from now, we’ll effectively reduce the burden of these inflammatory mood disorders through vaccination. Until then, scientists continue on with innovative approaches to tackle this prescient issue.