Bad air quality significantly linked to increased rates of bipolar disorder in US and Denmark
Poor air quality is significantly associated with higher rates of bipolar disorder and increases likelihood of major depression in both the US and Denmark, claims a new study. The trend appeared even stronger in Denmark, where exposure to polluted air during the first 10 years of a person’s life also predicted a more than two-fold increase in schizophrenia and personality disorders, says the research team from University of Chicago; Aarhus University, Denmark; University of California Los Angeles; Karolinska Institutet, Stockholm; and University of North Carolina.
The increasing prevalence of mental disorders is a major global problem that affects millions of people every year. In addition to personal suffering, psychiatric disorders are associated with high societal costs.
“These neurological and psychiatric diseases - so costly in both financial and social terms - appear linked to the physical environment, particularly air quality. The physical environment, air quality, in particular, warrants more research to better understand how our environment is contributing to neurological and psychiatric disorders,” says computational biologist Atif Khan, the first author of the study from the University of Chicago.
Researchers are increasingly studying the effects of “environmental insults” on psychiatric and neurological conditions, motivated by emerging evidence from extreme environmental events. Although mental illnesses such as bipolar disorder and schizophrenia develop due to a complex interplay of genetic predispositions and life experiences or exposures, genetics alone does not account entirely for variations in mental health and disease, says the research team.
Scientists have long suspected that genetic, neurochemical, and environmental factors interact at different levels to affect the onset, severity, and progression of these illnesses, says the study. For the current project, the team worked for over two years, enhancing their models with additional mathematical analyses and data sources.
The findings have been published in PLOS Biology.
The study looked at two independent datasets
To quantify air pollution exposure among individuals in the US, the University of Chicago team relied on the US Environmental Protection Agency’s measurements of 87 air quality measurements. For individuals in Denmark, they used a national pollution register that tracked a smaller number of pollutants with much higher spatial resolution.
The research team then examined two big population data sets, the first being a US health insurance claims database, which includes 11 years of claims for 151 million individuals from 2003-2013. The second dataset consisted of all 1.4 million individuals born in Denmark between January 1, 1979, and December 31, 2002, who were alive and residing in Denmark on their tenth birthday.
Because Danes are assigned unique identification numbers that can link information from various national registries, the team was able to estimate exposure to air pollution at the individual level during the first ten years of their life. In the US study, exposure measurements were limited to the county level.
The findings
For the US cohort, the researchers studied four psychiatric and two neurological conditions: bipolar disorder, major depression, personality disorder, schizophrenia, epilepsy, and Parkinson's disease. The team considered several environmental factors for the prediction of neurological and psychiatric disease diagnosis among different age and sex groups at the county level, including the quality of air, water, land, built environment, and weather conditions. In addition, population density, median income, ethnic and racial composition, and the percentages of poor and insured populations were also included in the model.
In the US population study, analysis shows that counties with the worst air quality had a 27% increase in bipolar disorder and a 6% increase in major depression when compared to those with the best air quality. The team also found a strong association between polluted soil and an increased risk of personality disorder.
“The worst air quality was associated with an approximately 27% increase in the apparent rate of bipolar disorder. The estimated rate of bipolar disorder was 16.4% higher in the most densely populated counties. For major depression, a slight increase of 6% in the diagnosis rate was observed only among the worst air quality regions. The regions with worst land quality were associated with an estimated 19.2% increase in the apparent rate of personality disorder,” says the study. It adds, “The counties with the highest number of pleasant weather days were associated with an estimated 21.8% decrease in the rate of bipolar disorder.”
Because these correlations seemed unusually strong, the team sought to validate their findings by applying the methodology on data from another country. Accordingly, for the Danish cohort, the researchers analyzed four psychiatric disorders: bipolar disorder, schizophrenia, personality disorder, and depression.
The team found that the associations, especially for bipolar disorder, mirrored those in the US: a 29% increase for those in counties with the worst air quality. Using this more specific Danish data, the team discovered that early childhood exposures correlated even more strongly with major depression (a 50% increase); with schizophrenia (a 148% increase); and with personality disorders (a 162% increase) over individuals who grew up in areas with the highest quality air.
The estimated rate of schizophrenia was 148% higher among individuals in the group with the highest exposure to air pollution compared with those with the least exposure. The strongest association was between air pollution and personality disorder, showing a 162% increase in the disorder rate. The estimated rate of major depression increased by 50.5% among the group with the highest exposure to air pollution,” the findings state.
It adds, “The association between air quality and the risk of all four psychiatric disorders remained statistically significant even after correcting for multiple comparisons.”
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Results from both studies, says the team, show that air pollution is significantly associated with increased risk of psychiatric disorders. “In our exploratory analysis, we found that poor air quality is associated with apparently higher rates of bipolar disorder and major depression in both US and Danish populations,” says the study.
“The Denmark analysis suggests that poor air quality during the initial years of an individual’s life increases the risk of all four psychiatric disorders studied here (bipolar disorder, schizophrenia, personality disorder, and major depression). In the US data, we see a similar trend for bipolar disorder, and to some extent for major depression, as that in Denmark, but the signal for schizophrenia and personality disorder is absent. It is likely that this difference is due to the limited resolution of the pollutant exposure estimates for the US data.
The researchers explain that air pollution is a complex and variable mixture of small particulate matter (PM), gases, metals, and organic contaminants generated by transport vehicles, industrial activity, and fires. Growing evidence from human, animal, and in vitro studies, says the team, is beginning to provide insight into how components of air pollution can be toxic to the brain. For example, recent studies on rodents suggest that environmental agents like ambient small particulate matter (fine dust) travel to the brain through the nose and lungs, while animals exposed to pollution have also shown signs of cognitive impairment and depression-like behavioral symptoms.
While the study did not address the question of how air pollution might trigger neural effects, a large body of experimental studies in animal models suggests that polluting chemicals affect neuroinflammatory pathways and set the stage for later neurodevelopmental problems - many of which occur at the end of childhood as children become adults.
“We hypothesized that pollutants might affect our brains through neuroinflammatory pathways that have also been shown to cause depression-like signs in animal studies,” says Andrey Rzhetsky from the University of Chicago, who led the study.
The findings have sparked controversy
The study findings are not without controversy: other researchers in the field have noted that this substantial correlation still does not confirm pollution actually triggers the diseases. Rzhetsky’s previous work on the correlation between air quality and asthma - which used a similar methodology - met with no resistance from journals or the broader scientific community. Rzhetsky adds that in experiments on animals exposed to pollution, the animals show signs of cognitive impairment and depression-like behavioral symptoms.
The divided opinions of the expert reviewers prompted PLOS Biology to commission a special companion article from Professor John Ioannidis of Stanford University. Though Ioannidis is unconnected with the study, he assisted the journal with the editorial process.
In the commentary, Ioannidis says that both data sets harness enormous sample sizes, but this offers no guarantee of validity. While the researchers have provided a “brilliant exploratory analysis with interesting hypothesis-generating hints for bipolar disorder and possibly other psychiatric diagnoses,” it will be useful to have analyses also done by other investigators, including researchers who may have skeptical views about the association of air pollution and mental health.
“A causal association of air pollution with mental diseases is an intriguing possibility raised in a short report just published in PLOS Biology. Despite analyses involving large data sets, the available evidence has substantial shortcomings, and a long series of potential biases may invalidate the observed associations. The only bipolar disorder shows consistent results, with similar effects across the US and Denmark data sets, but the effect has modest magnitude. More analyses by multiple investigators, including contrarians, are necessary. Broader public sharing of data sets would also enhance transparency,” says Ioannidis in the commentary.