Childhood Exposure to Air Pollution Linked to Increased Risk of Schizophrenia

Childhood exposure to the air pollutant nitrogen dioxide (NO2) is associated with an increased risk of developing schizophrenia, according to the findings of a recent study which appeared in JAMA Network Open.

This population-based cohort study comprised of 23,355 individuals (51.3% male) with schizophrenia and a randomly selected sub-cohort. Using national registry data, all individuals born in Denmark between May 1, 1981, and December 31, 2002, were followed up from their 10th birthday until the first occurrence of schizophrenia (the primary endpoint), emigration, death, or December 31, 2012, whichever came first. Statistical analyses were conducted between October 24, 2018, and June 17, 2019 using adjusted hazard ratios (AHRs) for schizophrenia with 95% Cis according to NO2 exposure. Polygenic risk scores were calculated as the weighted sum of risk alleles at selected single-nucleotide polymorphisms based on genetic material obtained from dried blood spot samples from the Danish Newborn Screening Biobank and on the Psychiatric Genomics Consortium genome-wide association study summary statistics file.

According to the results of the study, during the period of the study, 3,531 subjects were diagnosed with schizophrenia. The researchers observed that higher polygenic risk scores were linked with higher childhood NO2 exposure (ρ = 0.0782; 95% CI, 0.065 to 0.091; P < .001). Moreover, they found that a 10-μg/m3 increase in childhood daily NO2 exposure (AHR, 1.23; 95% CI, 1.15 to 1.32) along with a 1-SD increase in polygenic risk score (AHR, 1.29; 95% CI, 1.23 to 1.35) were both independently correlated with an augmented risk of developing schizophrenia.

“Potential biological mechanisms for the association between air pollution and schizophrenia remain uncertain, but air pollutants have been purported to cause inflammation of the tissue of the nervous system, oxidative stress, microglial activation, protein aggregation, subclinical cerebrovascular disease, and disruption of the blood-brain barrier,” the study authors wrote.

“With the complex clinical features of schizophrenia, it is likely that genetic variation may play a role in determining an individual’s susceptibility to the damaging effects of air pollution. However, our findings suggest that a polygenic risk score based on common variants related to schizophrenia cannot account for the association between childhood NO2 exposure and schizophrenia.”

They added that these results “demonstrate the utility of including polygenic risk scores in epidemiologic studies.”