For years, various studies have probed the links between air pollution and risk for diseases, especially heart and lung issues. More recently it’s been shown that people inhaling higher levels of air pollution may also be at higher risk for brain conditions like Alzheimer’s, worse decision-making, and depression.

Now one of the largest studies to date has focused on the connection between several forms of air pollution and the risk for developing late-life depression, with concerning results.

The paper, published in February in JAMA Network Open, tracked almost 9 million Medicare participants in the United States to look at the relationship between air pollution and the risk for developing depression in subsequent years. In this cohort study, researchers plotted people’s geographically-determined exposure to three separate air pollutants—PM2.5, nitrogen dioxide, and ozone—and then watched to see who was diagnosed with depression.

Because the participants in this study were enrolled in Medicare, they were all at least 64 years old at the time they began the study (the average age was around 74). The population was 57% females. Additionally, in order to minimize the chances that people’s depression was a pre-existing issue, they didn’t start tracking new cases of depression until five years after people began the study.

At the conclusion of this study, the researchers found that all three forms of air pollution individually and in combination correlated with an increased risk for developing depression. It was notable that among the three air pollutants, higher levels of ozone exposure had the strongest link to developing late-life depression.

This study was certainly not the first to point out the association between mental health and air pollution exposure. However, the large sample size and differential categorization of the effects of the three different air pollutants make it relatively unique. It’s important to note that scientists aren’t fully certain as to the biological mechanisms that connect depression and air pollution, but activation of inflammatory pathways in the brain is a leading possibility.

Inflammation, once considered more an acute rather than chronic threat, has in recent years emerged as a potential driver of a wide variety of neurological and psychological conditions. Within the brain it’s thought that inflammation could lead to a number of damaging effects including problems with neuron health as well as an unhealthy activation of immune cells called microglia.

Specific to air pollution, animal research has demonstrated that inhaled pollution significantly increased brain inflammatory markers, suggesting a lung-brain inflammatory mechanism. This is consistent with findings in humans. For example, in one 2016 study, researchers looked at brains of people after death and found that those exposed to more significant air pollution demonstrated higher levels of inflammatory markers in multiple parts of the brain including the prefrontal cortex and hippocampus, two areas linked to Alzheimer’s and depression symptoms.