Exposure to air pollutants may amplify risk for depression

• Exposure to air pollution is associated with cognitive deficits and an increased risk of depression.
• A recent study examined how air pollutants impact brain networks to mediate changes in cognitive function and enhance the risk of depression.
• The results suggest that genetic susceptibility to depression combined with high levels of exposure to air pollution have a disproportional effect on brain networks involved in cognition and stress.
• Exposure to air pollutants was associated with activation of brain networks expressing depression-associated genes, suggesting that exposure to air pollution may cause adverse mental health effects by acting on the same brain networks related to genetic mechanisms of depression.
• This suggests that individuals with a genetic susceptibility to depression may be more vulnerable to the adverse effects of air pollution on mental health.

Besides having a detrimental effect on physical health, prolonged exposure to air pollutants is also associated with adverse mental health effects.

Exposure to air pollutants, including fine particulate matter, may be associated with impaired cognitive functioning and depression.

Fine particulate matter, also known as PM2.5, consists of tiny inhalable particles smaller than 2.5 microns. These particles commonly come from industrial sources and vehicles.

How exposure to PM2.5 might increase the risk of depression is not well understood.

Also, scientists do not know whether air pollution can interact with a genetic predisposition for depression to increase the likelihood of depression.

Individuals with a genetic predisposition for a particular disease may have an increased likelihood of developing the condition in the presence of certain environmental factors or due to behaviors such as smoking.

A recent study investigated the effects of PM2.5 exposure, in combination with a genetic predisposition for depression, on brain networks involved in cognition and social stress.

The study’s lead author, Dr. Hao Yang Tan, a scientist at the Lieber Institute in Baltimore, MD, told Medical News Today:

“The study reveals for the first time how air pollution and genes interact with one another to impact important cognitive and emotional circuitry of the brain. Air pollution is changing the expression of genes that are conducive to depression.”

“Previous studies have observed air pollution’s link to depression, but our results are the first to show a direct, neurological cause,” he explained.

“What is most intriguing is that the two factors are linked in such a way that they have a multiplier effect on one’s risk of depression. That is, together, risk genes and bad air raise the risk of depression much more than either factor does in isolation.”

The study appears in the journal Proceedings of the National Academy of Sciences.

Cognition and trait anxiety

The study recruited 352 healthy participants residing in Beijing, China. Beijing has relatively high levels of air pollution, including high concentrations of PM2.5.

For each participant, the researchers studied several specific genetic variants that are associated with depression. From this information, they estimated their genetic susceptibility to depression.

To estimate the PM2.5 exposure levels for each individual, the researchers used air monitoring data obtained from the city air quality monitoring station closest to each person’s home for 6 months before the study.

Depression is associated with cognitive deficits and higher levels of anxiety-depression. In other words, these individuals have an increased tendency to react anxiously or with depressive symptoms to a situation. The scientists evaluated each participant’s levels of anxiety-depression using a questionnaire.

The researchers first examined the effects of PM2.5 exposure on cognition and characteristics associated with depression.

They found that PM2.5 exposure was associated with poor performance on cognitive tests involving reasoning and problem-solving. Higher anxiety-depression was also associated with PM2.5 exposure.

Brain connectivity

Next, the researchers examined brain networks involved in cognition and processing stress-related information and their association with PM2.5 exposure and genetic risk for depression.

The researchers measured the participants’ brain activity while conducting a simple cognitive task using functional magnetic resonance imaging.

To evaluate the influence of social stress on brain activity during the cognitive task, researchers showed the participants the image of a competitor and compared their performance with that of the competitor.

Higher levels of PM2.5 exposure were associated with slower reaction times during the cognitive task, and this effect of PM2.5 exposure became amplified during social stress.

Social stress had a more pronounced effect on brain networks in individuals with a genetic predisposition for depression and greater PM2.5 exposure.

The effect of social stress on brain networks due to the combination of genetic risk and air pollution was greater than the sum of the effects produced by each factor alone. These results suggest that air pollution may interact with genetic risk for depression to influence brain networks.

The dorsolateral prefrontal cortex is a brain region involved in several processes, including cognition. It was one of the key regions whose connectivity changed during the cognitive task in individuals with higher PM2.5 exposure and a genetic predisposition for depression.

Significantly, scientists have observed changes in the dorsolateral prefrontal cortex activity of healthy individuals with a genetic predisposition for depression and individuals with depression.

Depression-related brain networks

To further examine the interaction between genetic risk for depression and air pollution, the researchers investigated whether the combination of these factors differentially influenced brain networks involved in depression.

The researchers mapped the brain networks involved in depression by identifying brain regions expressing high levels of depression-associated genes.

The researchers used the online database Allen Brain Atlas, which provides detailed gene expression data for brain regions. They then identified brain regions that showed correlated expression of genes associated with depression.

The researchers examined if this pattern of coexpression of depression-associated genes in brain regions obtained using the atlas was similar to the brain connectivity patterns of the participants during the cognitive tests.

The pattern of coexpression of depression-associated genes derived using the atlas predicted brain connectivity patterns observed during the cognitive task. However, this was only the case for those with greater exposure to PM2.5 levels and a higher genetic predisposition for depression.

The correlation was weaker in individuals with a lower genetic risk of depression or lower exposure to PM2.5.

This suggests that exposure to PM2.5 air pollutants affects brain network functions associated with the genetic mechanisms of depression.

The researchers also conducted similar analyses focused on the association between the connectivity patterns of the dorsolateral prefrontal cortex with other brain regions and the coexpression of depression-associated genes in these regions.

The co-expression of depression-associated genes tracked the connectivity patterns to and from the dorsolateral prefrontal cortex in individuals with a genetic risk for depression, higher PM2.5 exposure levels, or both.

Interestingly, the co-expressed genes that correlated with brain connectivity patterns of the prefrontal cortex included some involved in neuroinflammation.

Depression is associated with chronic, low-grade inflammation, further suggesting that PM2.5 exposure may interact with depression-associated genes to increase the risk of depression.

“This is possibly the first study to directly implicate how genes for brain disorders operate in concert with each other and affect important cognitive and emotional functions in the live functioning brain, and the impact of air pollution and genes in multiplying the effects of each on these brain functions,” Dr. Tan told MNT.

“It is now [in] much less doubt that there are direct impacts of air pollution on how genes operate in the brain to affect risk for these neuropsychiatric disorders,” he added.

Implications

Dr. Tan noted: “Individuals can limit their outdoor activities when pollution is high and be mindful of their risk. Our study would strongly suggest that individuals with genetic risk, e.g., [a] family history of brain disorders, may need to be more careful, and minimize [as much as] possible their exposures to any air pollution.”

“Armed with this knowledge, leaders and public health officials around the globe have ample evidence that additional air pollution controls will lead to lower rates of depression — particularly in densely populated urban areas where air pollution is highest, and stress from socioeconomic and other inequities are greater.”

– Dr. Tan

Dr. Perry Sheffield, an environmental health researcher at Icahn School of Medicine at Mount Sinai, New York, noted that this study “helps drive home the point that when we talk about vulnerable groups — and here I mean groups of people who are more likely to experience negative health effects from a certain environmental exposure — we are ultimately talking about all of us. Each of us is vulnerable probably in multiple ways, and our specific vulnerabilities change during our lives.”

“Vulnerability can certainly be socially and unjustly determined — as we see driving racial and ethnic health disparities — but it can [also be] influenced by underlying genetics, as we see here in relation to air pollution and depression, and certainly by life stage or age,” she continued.

“The value of illustrating these associations in a study like this is that it helps tell the story of why clean air, water, and the overall environment matter for the health of people and communities.”

– Dr. Sheffield

Strengths and limitations

Dr. Tan explained to MNT, “An important strength is that we have studied the brain impacts of air pollution using arguably the most direct measurements of live human brain function, which is MRI technologies.”

“We have studied a large sample of individuals. We have also eliminated many other factors that could have interfered with the study.” For instance, their sample was “socioeconomically homogeneous.”

“We have additionally examined patterns of how risk genes for depression operated in concert with each other in postmortem human brains and found that these patterns corresponded well with how the live human brain operated, and especially so in individuals with genetic risk for depression and exposed to high air pollution.”

Dr. Tan acknowledged that there were a few limitations to their approach, saying the team “studied only a limited set of genes for depression, and that’s likely only the tip of the iceberg.”

“There are likely many other genes [for] neuropsychiatric disorders implicated in the brain impacts of air pollution. Understanding these more comprehensively would enable us to better identify people at risk, and perhaps identify various pharmacological or other ways to protect the vulnerable,” he concluded.

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