Significant link between environmental pollution and neuro-psychiatric disorders

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A study led by University of Chicago researchers suggests a significant link between exposure to environmental pollution and an increase in the prevalence of neuro-psychiatric disorders. Based on analysis of large population data sets from both the US and Denmark, the study found poor air quality associated with increased rates of bipolar disorder and major depression in both countries.

“Our studies in the US and Denmark show that living in polluted areas, especially early in life, is predictive of mental disorders,” said computational biologist Atif Khan, the first author of the new study. “These neurological and psychiatric diseases – so costly in both financial and social terms – appear linked to the physical environment, particularly air quality.”

Khan and Andrey Rzhetsky, the Edna K Papazian professor of medicine and human genetics and the paper’s senior author, used a US health insurance database of 151m individuals with 11 years of inpatient and outpatient claims for neuro-psychiatric diseases. They compared the geo-incidence of claims to measurements of 87 potential air pollutants from the United States Environmental Protection Agency. The counties with the worst air quality had a 27% increase in bipolar disorder and 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.

Because these correlations seemed unusually strong, the team sought to validate their findings by applying the methodology on data from another country. Denmark tracks environmental quality indicators over much smaller areas (a little over one-quarter of a mile) than does the EPA. The UChicago team collaborated with Denmark-based researchers at Aarhus University to analyse Danish national treatment registers with data from 1.4m people born in Denmark between 1979 and 2002. The researchers examined the incidence of neuro-psychiatric disease in Danish adults who had lived in areas with poor environmental quality up to their tenth birthdays.

The associations the team found, 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 found 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.

Researchers have long suspected that genetic and neuro-chemical factors interact at different levels to affect the onset, severity and progression of these illnesses. So far, scientists have found only modest associations between individual genetic variants and neuro-psychiatric disease: for most common polymorphisms, disease risk increase is small, perhaps less than 10%. This fact led Rzhetsky, who has been studying the genetic roots of a wide variety of neuro-psychiatric diseases for over two decades, to look for other molecular factors that might trigger or contribute to the disease mechanism.

Khan, Rzhetsky and the team worked on the project for over two years, enhancing their models with additional mathematical analyses and data sources. Nevertheless, their 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 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 behavioural 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 neuro-inflammatory pathways and set the stage for later neuro-developmental problems – many of which occur at the end of childhood as children become adults.

Abstract
The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.

Authors
Atif Khan, Oleguer Plana-Ripoll, Sussie Antonsen, Jørgen Brandt, Camilla Geels, Hannah Landecker, Patrick F Sullivan, Carsten Bøcker Pedersen, Andrey Rzhetsky

The University of Chicago material
PLOS Biology abstract


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