Summary: Children who grow up in areas with high levels of air pollution face a higher risk of being diagnosed with schizophrenia later in life.
Source: Aarhus University
Overview
Air pollution is known to harm physical health, and new research from Aarhus University indicates it may also affect mental health. A Danish population-based study that links genetic data from the iPSYCH project with environmental exposure data from the Department of Environmental Science finds that higher childhood exposure to nitrogen dioxide (NO2) is associated with an increased risk of developing schizophrenia.
The study’s lead investigator, Senior Researcher Henriette Thisted Horsdal, reports that risk rises with greater NO2 exposure. Specifically, for every 10 μg/m3 increase in mean daily NO2 exposure during childhood, the risk of schizophrenia increases by about 20 percent. Children exposed to an average daily NO2 level above 25 μg/m3 had roughly a 60 percent higher risk of schizophrenia compared with children exposed to levels below 10 μg/m3.
To contextualize these percentages: the lifetime risk of schizophrenia in the general population is approximately two percent. In this study, people with the lowest childhood NO2 exposure had a lifetime risk just under two percent, whereas those with the highest childhood exposure had an approximate lifetime risk of three percent.
Unknown cause
The findings were published in the peer-reviewed journal JAMA Network Open.
Importantly, the researchers examined both environmental exposure and genetic susceptibility. The study shows that genetic liability—measured by a polygenic risk score for schizophrenia—is independently associated with schizophrenia risk. The association between childhood NO2 exposure and schizophrenia remains after accounting for genetic risk, indicating that the increased schizophrenia risk linked to air pollution cannot be fully explained by a higher genetic predisposition among people who live in more polluted areas.
The research included 23,355 individuals, of whom 3,531 were diagnosed with schizophrenia during follow-up. While the results point to a clear association between higher childhood NO2 exposure and elevated schizophrenia risk, the authors emphasize that causation has not been established. They call for further research to investigate the biological and environmental mechanisms underlying this relationship.
Study background and design
This register-based, population cohort study combined national registry data with genetic and environmental exposure measures. The cohort comprised individuals born in Denmark between May 1, 1981, and December 31, 2002. Participants were followed from their 10th birthday until the first occurrence of schizophrenia, emigration, death, or December 31, 2012.
Childhood NO2 exposure was calculated as the mean daily concentration at residential addresses from birth to the 10th birthday. Genetic liability was assessed using polygenic risk scores derived from newborn dried blood spots and genome-wide association summary statistics. The main outcome measured was a diagnosis of schizophrenia (ICD-10 code F20).
Key results
Of the 23,355 participants (51.3% male), 3,531 received a schizophrenia diagnosis during the study period. The study found a modest positive correlation between higher polygenic risk scores and greater childhood NO2 exposure. After statistical adjustment, a 10 μg/m3 increase in mean daily childhood NO2 exposure was associated with an adjusted hazard ratio (AHR) of 1.23 for schizophrenia (95% CI, 1.15–1.32). A one-standard-deviation increase in the polygenic risk score was associated with an AHR of 1.29 (95% CI, 1.23–1.35). Both exposures were independently associated with schizophrenia risk.
Conclusions and implications
The findings indicate that the link between childhood NO2 exposure and schizophrenia risk is only partly explained by genetic predisposition. The results underline the value of incorporating polygenic risk scores into epidemiologic research to disentangle environmental and genetic contributions to disease. The authors recommend additional studies to clarify causality and to investigate potential mechanisms by which air pollution might influence neurodevelopment and psychiatric outcomes.
Funding
This research was funded by the Lundbeck Foundation.
Source:
Aarhus University
Media contact:
Henriette Thisted Horsdal – Aarhus University
Image source:
The image is in the public domain.
Original research
Title: Association of Childhood Exposure to Nitrogen Dioxide and Polygenic Risk Score for Schizophrenia With the Risk of Developing Schizophrenia. Henriette Thisted Horsdal et al. JAMA Network Open. DOI: 10.1001/jamanetworkopen.2019.14401 (open access).