Could air pollution contribute to psychiatric illness?

Poor air quality has been associated with higher rates of bipolar disorder and major depression in observational research involving more than 150 million people in the US and Denmark. 

The link was found to be more pronounced in Denmark, with research also suggesting that pollution exposure during childhood more than doubled the risk of schizophrenia and personality disorders.

Genetic studies now reveal that genes only explain a small fraction of psychiatric illness onset. Therefore, researchers are exploring environmental factors in the search to comprehend the global increase in these complex disorders of brain function.

“We were hoping to understand what aspects of human environments are driving psychiatric and neurological disease prevalence,” says senior author Andrey Rzhetsky from the University of Chicago, US. 

The findings are published in the journal PLOS ONE.

The search thus far has focussed largely on family environments and childhood trauma, including prenatal influences. Other possible avenues include social circumstances, stressful life events, substance abuse, and emerging evidence for poor diet.

Far less attention has been given to physical environments. Yet as the numerous adverse health impacts of air pollution have come to light, inspection of its potential role in neurological disorders has lagged.

To address this, Rzhetsky and colleagues turned to two large, independent datasets for answers. 

The US dataset comprised a decade of insurance claims for more than 151 million people, linked to environmental reports of air quality at the county level by the Environmental Protection Agency. {%recommended 6826%}

The Danish analysis was derived from a collection of national treatment and pollution registers including nearly one and a half million people born between 1979 and 2002, with data on individual-level exposure to air pollution during their first 10 years of life.

After controlling for variables such as population density, income and ethnicity, and correcting for dependence on spatial data, the poorest air quality in the US correlated with a 29% increased risk of bipolar disorder compared to the cleanest air. It was also the strongest environmental predictor of the condition. 

For major depression, an increase of 6% in diagnosis rates was revealed in regions with the worst air quality. Personality disorders were 25.9% higher in areas with the poorest land quality.

Epilepsy and Parkinson’s disease – two neurological conditions also included in the analysis – did not show any association.

All four disorders tested in Denmark – after adjusting for confounding factors – were strongly linked with childhood exposure to air pollution. Schizophrenia increased by 148% with high versus low exposure, personality disorder by 162%, bipolar by 29.5% and depression by 50.5%.

Associations with these psychiatric conditions all remained after the two datasets were merged.

The researchers turned to mechanistic studies for insights, finding that inflammation – previously linked to heart problems as a result of air pollution – is a possible contender.

“In a nutshell, extrapolating from animal studies: pollution can reach the brain and induce (neuro)inflammation, which results in depression-like symptoms in animals,” says Rzhetsky.

From these studies, the researchers conclude, “it is clear that both systemic and direct nose-to-brain routes generate neuroinflammation and oxidative stress”.

Inflammation has also been linked to psychiatric disorders in humans, including bipolar disorder, major depression, and schizophrenia.

But the findings incited divided opinions from reviewers, prompting the journal to commission a commentary from John Ioannidis – who was not involved in the study – from Stanford University.

“A causal association of air pollution with mental diseases is an intriguing possibility,” Ioannidis writes. But he highlights shortcomings and biases that could invalidate the findings, concluding, “More analyses by multiple investigators, including contrarians, are necessary.”

Despite the strength of the large dataset, Rzhetsky agrees that associations do not necessarily equate to causation. He says he’s not entirely sure why the findings generated so much controversy though. 

“Possibly, because the results are unexpected,” he suggests. “For example, our recent paper on analogous analysis related to asthma created little controversy or resistance.”

The researchers advocate for further investigation of smog as an environmental contributor to mental illness, pointing to the importance of examining “whether air pollution’s neuroinflammatory impacts share common pathways with other stress-induced conditions”.