Poor air quality is associated with higher rates of multiple psychiatric disorders, new research shows.
Analyzing large data sets from the US and Denmark, researchers found significant correlations between air pollution and bipolar disorder in both countries, as well as between air pollution and depression, schizophrenia, and personality disorder in Denmark.
"If we know which environmental factors can cause disease, we can probably prevent them in some patients, especially if we know they are genetically vulnerable." Andrey Rzhetsky, PhD, professor of medicine and human genetics at the University of Chicago, Ill., Reported Medscape Medical News.
The results were published online on August 20 in PLOS Biology.
A Complex Mixture
Heritability greatly explains the development of psychiatric disorders, but "it's never 100%", and it's becoming increasingly apparent that environmental pressures play an important role, Rzhetsky said.
Air pollution is a complex mixture of small particles, gases, metals and organic pollutants, which are the result of natural erosion of stone and man-made materials, exhaust from transport vehicles, industrial activities and fires.
There is already evidence from humans, animals, and in vitro studies that air pollutants enter the brain and are implicated in the etiology of neurological and psychiatric disorders.
For the current study, the researchers performed two analyzes, one with US data and the other with Danish data.
It is impossible to have the same design for the two datasets, Rzhetsky said. He added that the two countries pursue different cultures and different approaches to health care, population tracking and environmental monitoring.
For the US analysis, investigators used the IBM MarketScan health insurance database, which includes inpatient and health insurance, outpatient claims, medical interventions, and prescription drugs for more than 151 million patients over the period 2003-2013.  Their analysis included the quality of air, water and soil (eg chemicals in the soil) and the "built" environment (eg vehicle traffic, transit traffic and pedestrian safety).
To quantify air pollution, researchers used the Environmental Protection Agency's Air Quality Index, which is a summary measure of 87 potential air pollutants. Rzhetsky noted that the researchers performed air quality measurements for this analysis only at one time and at the county level.
Researchers turned environmental predictors into septiles, with Q1 showing the best quality and Q7 the worst quality.
This analysis evaluated four psychiatric disorders – bipolar disorder, major depression, personality disorder and schizophrenia – and two neurological disorders – Parkinson's disease (PD) and epilepsy. The neurological disorders served as controls and "we did not expect to find an association," said Rzhetsky.
The results showed that the worst air quality was associated with about 27% of the best air quality. Percent increase in the rate of bipolar disorder (95% Credible interval, 15% – 40%; P <10 -4 ).
In severe depression, there was an increase of 6% in the diagnosis rate in the worst and best air quality regions.
The US data also showed a correlation between personality disorder and poor land quality, but not air pollution.
There was no association between poor water quality or "built" environment and psychiatric disorders, nor was there any association between any type of pollution and epilepsy or PD.
Exposure of children
For the Danish analysis, researchers used national treatment and pollution registers covering more than 1.4 million people born between 1979 and 20 years 02 who were living in Denmark for their 10th birthday.
They examined the association between exposure to air pollution from children and the same four psychiatric disorders included in the US analysis, but did not rate neurological disorders.
Component analysis on 14 air quality indicators to obtain a summarized measure of exposure to air pollution. They re-converted this exposure into septiles, with Q1 the lowest exposure and Q7 the highest exposure.
Using the Danish registries, the researchers were able to track each person's movements over time and access historical pollution data at a distance of 1 km x 1 km cell size. This allowed them to assess exposure to air pollution at the individual level, which is "much more accurate" than the level of exposure used at the county level in the US analysis, Rzhetsky said.
The results showed that the rate of all four psychiatric disorders increased with increasing exposure to air pollution. The strongest association was for personality disorders, for which an increase of 162% (95% confidence interval, 142% – 183%; P <2 × 10 – 16 ) in the rate for category Q7 compared to category Q1.
For bipolar disorder, the estimated rate in group Q7 was 24.3% higher than in group Q1.
Sub-analyzes of the data included a "spatial dependency correction" that took into account the proximity of US states with potentially shared environments and "harmonization" of the two sets of data.
These additional analyzes generally supported the robustness of the main findings, the authors of the study noted.
] The most likely mechanism by which pollutants cause psychiatric illness is neuroinflammation. "We have a whole range of evidence from animal studies, for example in dogs, and anecdotal evidence in humans," said Rzhetsky.
The researchers note that it is impossible to pinpoint certain airborne compounds that could lead to mental illnesses; It is likely that several pollutants contribute in an additive or synergistic way to negative effects on the human nervous system.
However, there are "some suspects", including small environmental particles that can enter the lungs and bloodstream or pass through the blood brain barrier, Rzhetsky said. "They can also get to the brain via the olfactory system, which is a more direct route as we have olfactory neurons in the nose," he added.
He is convinced that stopping a neuroinflammation can reverse the psychiatric symptoms.
This needs to be reviewed, which can be a challenge. Rzhetsky pointed out that clinical trials can not be conducted because it is "completely unethical" to expose people to adverse environmental conditions for study purposes.
In an accompanying editorial, John PA Ioannidis, MD, director, Prevention Research Center, Stanford University, California, and director of the Meta-Research Innovation Center at Stanford, wrote that a causal link exists between air pollution and pollution mental illness is a "fascinating possibility" and that the current study makes a valuable contribution to research field.
The researchers "have provided a brilliant exploratory analysis with interesting hypothesis-generating evidence of bipolar disorder and possibly other psychiatric diagnoses," writes Ioannidis.
But he notes some shortcomings of the study, including the fact that the "huge sample sizes" of the datasets do not guarantee validity.
"The analysis of big data can make absurd conclusions about fundamental flaws in the quality of the data," he writes. "The US database is about 100 times larger than the Danish one, but the latter is of better quality."
Other notable differences are the differences between exposure measurement datasets and the number of variables used to define air pollution.
Moreover, the strength of the observed associations is "modest"; According to Ioannidis, the effect sizes are larger in the Danish data, but they never reach a relative risk of more than 3.
"However, this is not necessarily a weakness, it has been argued that most true causal effects are modest or even low are / tiny, too big effects can easily point to errors and distortions, "he writes.
The researchers also seem to interpret their findings as "replicated transnationally," he writes. "However, with the exception of bipolar disorder, the point estimates between the US and Denmark are strikingly different and the 95% confidence intervals do not even overlap."
It would be useful to have research done by other researchers, including such Ioannidis concludes that he may have "skeptical views" about the relationship between air pollution and mental health.
"Notable" Bipolar Outcomes
Commentary for Medscape Medical News Carson City, Nevada, Carson Tahoe Health, Carson City, Nevada, member of the Caucus on Climate Change of the American Psychiatric Association, said The study was interesting and the illustrations particularly impressive.
"Only the maps themselves, which show the distribution of mood disorders and schizophrenia in the US and the spread of healthy environments of various kinds are intriguing," said Haase, who was not involved in the research.
She agreed with Ioan to Nidis that the Danish analysis is "a bit cleaner" than the US, also because it takes into account the pollution from children's pollution. An early neuroinflammation or genetic injury in the early years could represent a significant risk factor for a later pathology whole county, which is much more specific.
She added that it was "remarkable" that the results for bipolar disorder were so consistent, noting that there had been no studies on bipolar illness and air pollution. "This was a serious deficit
Haase emphasized that there are air pollution control options that could reduce neuroinflammation, including the generation of clean energy, the control of industrial pollutants, and the reduction of fossil fuel use.
There is "strong evidence" that diseases in areas of the United States where coal-fired power plants have been shut down are becoming less severe, she said.  The study was funded by the Nordforsk Project 75007, the DARPA Big Mechanism Program. funded by the National Institutes of Health and a gift from Liz and Kent Dauten The authors of the study, Ioannidis and Haase, have no relevant fi nancial relations reported.
PLoS Biol. Published online: August 20, 2019. Full Article, Editorial
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