As seen in Psychology Today.

Air pollution is a major problem throughout the world. There is a wide range of pollutants to which people can be exposed. Some chemicals, like those released in chemical spills or industrial fires, cause acute discomfort and illness even in relatively low concentrations. Other pollutants—like carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and particulate matter smaller than 2.5 microns in diameter (PM2.5)—may be less toxic when at low concentrations and in acute settings but become problematic when exposure is chronic. While overall emissions of toxic air pollutants have declined since the early 1990s, the health effects of air pollution continue to be felt by people old and young. Most assume that the damage caused by air pollution is limited to lungs, but research has shown that long-term exposure can have far more wide-ranging effects. There is some evidence linking trichlorethylene (a common industrial solvent) and NO2 to Parkinson’s disease, as well as particulate matter to memory deficits and Alzheimer’s disease. Poor air quality can also increase the risk of long Covid in younger populations and increase the risk of dementia and depression among older populations. This latter issue was highlighted recently by Qiu and colleagues’ paper in JAMA, which examined 8.9 million Medicare enrollees. Within this group, over 1.5 million late-onset major-depression diagnoses were reported. The authors found “statistically significant harmful associations were observed between long-term exposure to common levels of air pollution and increased risk of depression diagnosis after age 64 years, accounting for climate coexposures, neighborhood greenness, socioeconomic conditions, health care access, and urbanicity level.” The three criteria air pollutants included in their analysis were PM2.5, O3, and NO2.

Homeostasis, Stress Response, and Inflammation

To better understand how these pollutants can impact mental health requires an understanding of how the body responds to stressors. Homeostasis is a tendency exhibited by all organisms to maintain a stable state of equilibrium or dynamic balance. Homeostasis operates at multiple levels, including individual cells, tissue compartments, and specific systems within an organism. This includes the immune system, which will be the focus of this article.

In most cases, the body is protected from foreign substances by the skin and epithelial cells lining our digestive and reproductive tracts. When foreign substances, known as antigens, get past these defenses, they are identified by cells within the body’s immune system, and then neutralized, thereby restoring homeostasis. Antigens may be a pathogen (like a virion, bacterium, or fungus spore), an allergen, or a toxin.

In most cases, antigens are neutralized locally and do not require the mobilization of additional resources from the immune system. However, when the localized response is not enough, a stress response may be initiated to eliminate the antigen. If the stress response is not sufficient to return the body to homeostasis, this may trigger an inflammatory response.

Ordinarily, inflammation is not problematic. It is a healthy response to antigens and the body’s most intensive mechanism for restoring homeostasis. However, if the body is constantly under stress because it is constantly being exposed to antigens like air pollutants, this can lead to chronic inflammation, which can lead to insidious forms of tissue damage as elevated levels of immune cells put wear and tear on the body. In fact, individuals with chronic inflammation may not even feel sick or out of the ordinary, but pathologic responses may develop over time.

The Blood Brain Barrier and Neuroinflammation

For many years, chronic inflammation was believed to be something that spared the brain because it was assumed that it was protected by the blood brain barrier (BBB), a semipermeable membrane that separates the central nervous system (CNS) from the rest of the body. Recent studies have found that this is not entirely accurate, and that the CNS is constantly communicating with the peripheral immune system via neurotransmitters, hormones, and pro- and anti-inflammatory proteins released by immune cells known as cytokines.

These interactions can influence glial cells, which carry out neuronal support functions and regulate the brain’s specialized immune system, and astrocytes, which contribute to the immune system of the CNS and regulate the permeability of the BBB. Both astrocytes and microglia can produce pro- and anti-inflammatory cytokines. They can also initiate stress responses and inflammation—i.e. neuroinflammation.

What Does Neuroinflammation Feel Like?

In most cases, neuroinflammation is similar to the inflammatory response described above: it’s a more intensive mechanism for bringing the CNS back into a state of homeostasis. It is a crucial part of the neuroimmune system and neural tissue can regularly be temporarily inflamed as a response to stressors or pathogens without notice.

However, chronic states of neuroinflammation are different. In addition to physiological problems via neuronal damage, there are also psychological correlates to this phenomenon. In other words, neuroinflammation can manifest as problems with cognition, memory, and mood, including depressive symptoms.

Can We Cure Depression?

Here’s the rub. While there are clear associations between neuroinflammation and depressive symptoms (as well as other neurological and psychiatric diseases), the clinical studies designed to test the efficacy of anti-inflammatory agents have not produced clear and beneficial results. There may be any number of reasons why this is so, including an incomplete understanding of all the mechanisms involved in the process.

What does seem clear is that a preventative approach may be best, which means limiting air pollution to improve mental health rather than simply responding to symptoms and letting pollution stay at current levels. This is not a new or radical idea. Lead was once burned in gasoline, but we as a society eventually agreed that it led to health problems (including dysfunctions in children’s mental functioning) that were too serious to ignore, and we eventually phased it out.

There is no doubt that more extensive solutions will be required to remove major pollutants like PM2.5, O3, and NO2. However, one easy place to start is by requiring state and federal air quality standards to be stricter and to spread awareness about the effects of these pollutants on mental health.