BEIJING, CHINA - 2021/11/05: The sky over Beijing is shrouded in thick air pollution haze and visibi...

Even Worse Than You Think

Why air pollution can trigger depression

A genetic risk, combined with air pollution, can dramatically influence mental health.

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You may be breathing dirty air right now. Nine out of ten people in the world live in areas with high levels of air pollutants, according to the World Health Organization.

This is a problem for physical and mental health. In addition to its well-established relationships to cancer and respiratory and heart diseases, a growing trove of scientific evidence links air pollution with depression and other mental health disorders.

A study published Monday in the Proceedings of the National Academies of Sciences adds to our understanding of this relationship, revealing one mechanism by which air pollution may trigger depression.

Researchers at the Lieber Institute for Brain Development and Peking University in Beijing studied the genetic makeup of 352 healthy residents of Beijing for markers that show a predisposition to depression. High exposure to air pollution, in turn, was correlated to poor performance on mental exercises used to measure depression-related cognitive difficulties.

The people who struggled the most were both getting doused with pollutants and had the genetic markers for depression.

“It’s a multiplicative effect,” lead author Hao Yang Tan, an investigator at the Lieber Institute, tells Inverse. “It’s genetic risk combined with air pollution that dramatically increases the impact of air pollution on the brain.”

How the discovery was made — Researchers used genotyping to search for genetic markers associated with a risk for depression in each participant. This allowed them to create a polygenic depression risk score for each. It’s not a diagnosis, but a mathematical likelihood, based only on genetics, that a person will be affected by depression.

“This could be the tip of the iceberg. A lot of these genes overlap.”

One reason the researchers chose Beijing is that, by the standards of a ginormous city, its population is pretty genetically homogeneous.

“Almost everyone is Han Chinese,” co-author Daniel R. Weinberger, the C.E.O. and director of the Lieber Institute, tells Inverse. “This allowed the study to begin with a population where the main differences from one to another were their risk of depression.”

The researchers then tracked air pollution near the participants’ homes using data from the air quality monitoring stations stretched across Beijing.

Fortunately — for research and health purposes — shortly before the start of the study, Beijing implemented some changes to curb its notorious air pollution. Factories that were heavy polluters were closed or retrofitted and coal-fired burners were replaced by natural gas. The measures were gradual and only some areas saw immediate relief.

“That engineered very big variations in air pollution exposures across the study,” explains Tan.

Famously smoggy Beijing was implementing anti-air pollution measures during the study, providing researchers a useful span of variance in participants’ exposure.Andrea Verdelli/Getty Images News/Getty Images

Because they wanted to see how pollution influenced the brain in real-time, they utilized cognitive tests that indicate depression, as opposed to a method like mood questionnaires. The subjects also wore magnetic resonance imaging (MRI) equipment, so the researchers could look for brain patterns associated with depression.

As part of these tests, participants did a series of math problems. On some of those tests, the researchers subjected each to “social stress” by showing them a photograph of a “competitor” — a stranger of the same gender and approximate age, to whom their performance would be compared. They were told they lost after a round.

People with depression are prone to perform more slowly and less accurately in the face of negative feedback, the study team argues.

“They have poor concentration,” Tan says. “They are demoralized easily. They have negative self-thoughts, so these tests stimulate those cognitive and emotional dysfunctions.”

The people who were getting a heavy dose of pollutants but had no genetic predisposition to depression also fumbled. “Their brain functions were still relatively dysfunctional,” Tan explains. “Only individuals with low genetic risk and low air pollution exposures were a little bit better.”

He said the takeaway clear, though: The people who did the worst were most likely high in pollution exposure and polygenic depression risk score, indicating that the pollution activates those genes and multiplies their emotional and cognitive fumbling.

What’s new — Weinberg points to the number of previous studies which suggest people who live in high-pollution environments “had cognitive problems and were at an increased risk of depression.” However, these studies don’t show a causative relationship between these two factors.

“[T]here are a lot of reasons these associations might exist,” Weinberger says. “Pollution is more prevalent in cities. There are some signs cities make people depressed.”

The study team says this is the first study to cut out those factors and show a link between air pollution exposure and the brain’s working at a neurological level all while processing emotional and cognitive information.

Why this matters — Air pollution is a ubiquitous problem in the world's urban areas. Many places are seeing vast improvements to their air quality, including the U.S., China, and Europe. Others, like Central and Southern Asia and Sub-Saharan Africa, are experiencing worsening air.

Many mental and cognitive issues are possibly made worse by air pollution and many also have a genetic component. A study like this could be used to understand the interaction of environmental and genetic factors for several conditions.

Los Angeles is frequently on lists of cities with the worst air pollution.Mario Tama/Getty Images News/Getty Images

“This could be the tip of the iceberg,” Tan explains. “A lot of these genes overlap. Depression is important but [air pollution] probably affects other brain disorders, in younger people and older people, whether it’d ADHD, autism, or even dementia and other neurodegenerative conditions.

There are risk factors there that overlap, he says, and it’s space Tan thinks more people need to pay attention to. “Obviously, everyone is aware it causes lung and heart disease,” Tan says, “but the impact at the level of the brain, it’s much less understood.”

Abstract: Air pollution is a reversible cause of significant global mortality and morbidity. Epidemiological evidence suggests associations between air pollution exposure and impaired cognition and increased risk for major depressive disorders. However, the neural bases of these associations have been unclear. Here, in healthy human subjects exposed to relatively high air pollution and controlling for socioeconomic, genomic, and other confounders, we examine across multiple levels of brain network function the extent to which particulate matter (PM2.5) exposure influences putative genetic risk mechanisms associated with depression. Increased ambient PM2.5 exposure was associated with poorer reasoning and problem solving and higher-trait anxiety/depression. Working memory and stress-related information transfer (effective connectivity) across cortical and subcortical brain networks were influenced by PM2.5 exposure to differing extents depending on the polygenic risk for depression in gene-by-environment interactions. Effective connectivity patterns from individuals with higher polygenic risk for depression and higher exposures with PM2.5, but not from those with lower genetic risk or lower exposures, correlated spatially with the coexpression of depression-associated genes across corresponding brain regions in the Allen Brain Atlas. These converging data suggest that PM2.5 exposure affects brain network functions implicated in the genetic mechanisms of depression.