Introduction
Air pollution has been linked to an increasing array of mental health problems across the lifespan [
1]. In adults, depression and (to a lesser extent) anxiety have been shown to be associated with long-term exposure to particulate matter less than 2.5 μm (PM
2.5), and short-term exposure may be associated with completed suicide [
1]. Schizophrenia (and polygenic risk for schizophrenia) has been linked to childhood exposure to nitrogen dioxide (NO
2) [
2]. In addition, perinatal exposure to airborne particulate matter, particularly PM
2.5, has been associated with a variety of neurodevelopmental outcomes in childhood including autism spectrum and attention-deficit/hyperactivity disorders [
3,
4]. While these neurodevelopmental disorders are diagnosed in childhood, mental disorders such as schizophrenia are rarely expressed in childhood, making the trajectory of their association with childhood air pollution exposure difficult to trace [
5]. However, adult mental disorder is commonly preceded by childhood psychopathology [
6], and childhood emotional and behavioural symptoms and psychotic-like experiences can be measured by self-report [
7] for examination in relation to air pollution exposure.
Childhood Psychotic-like Experiences (PLEs) are relatively common, but children with more frequent or severe PLEs have a higher risk of developing schizophrenia in adulthood compared to children with more transient or no experience of PLEs [
8]. Only one previous study has examined the association between self-reported PLEs in childhood (using a Prodromal Questionnaire-Brief Child Version at age 9–10 years) and prior exposure to NO
2 and PM
2.5, reporting no association in models adjusted for a number of variables, including parental PLEs, family mental health history, and financial adversity [
9]. There has also been one study of these associations in relation to PLEs measured in adolescence: in a cohort of twins, exposure to NO
2 and PM
2.5 at age 18 years were each associated with psychotic experiences at the same age [
10]
, after adjusting for a range of covariates including urbanicity, socioeconomic status, substance misuse, and maternal psychosis. In addition to the above studies examining childhood and adolescent PLEs, prenatal exposure to polycyclic aromatic hydrocarbons (PAHs), produced by combustion of carbon-based compounds, was associated with early childhood adversity and a more general construct of
thought problems (which included some PLEs) on Achenbach’s Child Behaviour Checklist (CBCL) in middle childhood [
11].
More studies have examined associations between air pollution exposure and emotional symptoms in childhood, although results have been mixed. For example, only two studies reported a positive association between air pollution exposure in the perinatal period and depressive/anxiety symptoms. Perinatal PAH exposure was associated with parent-rated symptoms at age 6–7 years [
12] and perinatal (but not concurrent) traffic exposure was associated with parent, but not child-rated, symptoms age 12 years [
13]. Five other studies have reported no association between air pollution exposure in the perinatal period and childhood depressive/anxiety symptoms [
9,
14‐
17]. The effects of air pollution exposure in later childhood also remain unclear: exposure to NO
2 and PM
2.5 at age 12 years was not associated with concurrent depressive/anxiety symptoms but was associated with these symptoms at age 18 years [
18].
Similarly, conduct symptoms have been associated with air pollution in some studies but not others. Perinatal exposure to PM
2.5 and PAH has been associated with conduct symptoms in children ranging from 6 to 9 years [
19]. For example, NO
2 exposure at 9 months showed a small association with parent-rated conduct problems at age 3 years [
20]. However, there was a lack of association between perinatal air pollution and behavioural problems in a Japanese cohort at age 8 [
21]. Studies of later air pollution exposure and conduct symptoms have produced more mixed results. There was a strong association between exposure to PM
2.5 (but not NO
2) in the preceding 1–3 years and delinquent behaviour in a study of children and adolescents [
22], and there was an improved trajectory of self-reported conduct problems on the SDQ in middle school age children exposed to lower levels of NO
2 (as well as PM
2.5) in the preceding years [
23]. However, a study of 9–10 years old found no association between exposure to PM
2.5 and conduct problems around the same age [
9]. Further, in a twin cohort, there was no association between age 12 exposure to PM
2.5 or NO
2 and conduct symptoms at age 12 or 18 years [
10],
Given childhood PLEs have been sparsely studied in relation to air pollution despite known association with later psychotic symptoms and schizophrenia, we examined the associations between multiple types of air pollution and child reported PLEs in middle childhood (average age 11.5 years) using a large, population-based study of children in New South Wales (NSW) Australia. We also examined associations between air pollution and other mental health domains (emotional symptoms and conduct problems) to determine whether any associations with PLEs were limited to this construct, or more generally associated with childhood psychopathology. Given the heterogeneous results of previous studies which measured air pollution at ages varying from birth to 18 years, we chose two developmentally important time-points of exposure: birth and middle childhood (age 11.5 years). We considered several covariates used in the previous studies, including socioeconomic status, parental history of mental illness, and urbanicity [
10]. Aboriginal or Torres Strait Islander status was also considered, because Indigenous people are overrepresented in community cohort studies of mental disorders [
24]. We hypothesised that NO
2 would be more strongly associated with PLEs than emotional or conduct symptoms, given the consistent literature linking NO
2 with psychotic symptoms in a range of contexts. Further, we hypothesised that PM
2.5 would be most associated with conduct symptoms. We made no specific hypotheses about expected effects of the different exposure periods (birth or middle childhood) given mixed evidence of associations between air pollutants and childhood mental health symptoms in various developmental periods of exposure.
Discussion
This population cohort study of the association between air pollution exposure at two time-points (birth and middle childhood) and self-reported PLEs, emotional and conduct symptoms at a single time-point (mean age 11.5 years), revealed positive associations between exposure to NO2, and to a lesser extent PM2.5, in middle childhood and concurrent PLEs. This is a novel finding and, if replicated, raises the possibility that exposure to NO2 in the atmosphere could be involved in the development of psychotic-like experiences. It must be noted that effect sizes were small and as such, the clinical implications are uncertain given the unclear relationships between PLEs and later psychotic or other mental disorders. The lack of association between air pollution and middle childhood emotional symptoms and conduct problems in adjusted models suggests some specificity of this association. Further research is needed to identify if certain groups of children are more vulnerable to increased PLEs when exposed to NO2, and how this relates to later schizophrenia risk.
The small but significant association between exposure to NO
2 and PLEs in middle childhood is consistent with (but smaller than) previously reported associations between PLEs in late adolescence and concurrent exposure to NO
2 [
10], but inconsistent with a study of PLEs in 9–10 years old, where no association was found with exposure to PM
2.5 or NO
2 [
9]. However, in the latter study, NO
2 exposure was inferred from residential location at the same time as the PLE assessment (2016–2018) and then estimated using satellite data averaged over 3 years from 2010 to 2012; this may have introduced some measurement error, particularly if children had moved during those years. Given the small effect size in the current study, it seems plausible such a measurement error could obscure a small association. In addition, the current study suggests proximal exposure to NO
2 may be more important than more distal exposure (such as perinatal exposure), so that a study based on exposure many years prior may not detect a result. The similarity of the screening instruments, and the validity of using such instruments to assess PLEs suggest the choice of instrument is unlikely to significantly affect outcome [
31]; the robust current result, persisting with ordinal regression, suggests that the choice of outcome variable does not explain the inconsistent results across studies.
This study failed to replicate the previous findings of an association between perinatal NO
2 exposure and conduct symptoms [
20] (as well as more general externalising symptoms [
17]). Outcomes in these studies were measured at a much earlier age (preschool rather than middle childhood) and earlier onset symptoms may be more associated with air pollution. Our results are also inconsistent with a study demonstrating that NO
2 exposure in preceding years alters the trajectory of conduct problems in middle childhood [
17]. However, the current study did not examine the trajectory of conduct symptoms and it may be that air pollution influences trajectories of higher risk children, rather than cross-sectional conduct problem scores in the general population.
The lack of association between air pollution and emotional symptoms accords with the majority of studies in the area [
14‐
17]. One study which did find an association with childhood depressive symptoms was focused on a specific component of air pollution (PAH) that was not separately considered in this study [
12]. It may be that only certain components of PM
2.5 are associated with emotional symptoms and local differences in PM
2.5 composition may alter associations. The composition of PM
2.5 in Sydney in the summer of 2011 was around one-third sea salt and one-third organic matter with the remainder a mixture of soil, inorganic aerosols, and carbon; in autumn 2012, the mixture was almost two-thirds organic matter and only 5% sea salt [
45]. More detailed modelling of PM
2.5 components could help understanding of potential risks.
Since this study revealed associations between NO
2 exposure and some categories of childhood symptoms but not others, this raises questions about the possible mechanisms of action of NO
2. Proposed mechanisms, to date, have been based on post-mortem studies [
46] and animal models [
47] and centre on oxidative stress and cytokine release causing cell damage, after uptake through the olfactory nerve, or translocation from lungs and other organs [
48,
49]. Inflammation of the olfactory bulb has been linked to high air pollution exposure, though it seems likely other central nervous system sites are also affected [
50]. Studies on mechanisms have generally focused on PM
2.5, or air pollution as a whole, rather than NO
2. Further studies into the mechanism of action of NO
2 in children in conjunction with the existing research into general pollution and PM
2.5 in children [
46,
51,
52] could help address this question.
Strengths of this study include the large number of participants, the prospective, population-based design, and the access to linked data enabling adjustment for a number of key contributing factors. In the sampling, migrant populations were likely to be under-represented due to exclusion of those without a birth postcode in NSW. The other main methodological limitation of the current study relates to the measurement of pollution exposure. Exposure measures were assessed across large areas, which may have introduced measurement error. Several previous studies have used specific addresses and fine modelling to assess air pollution [
18] and this is preferable to area-based estimates. The effect sizes in the current study are small and it is difficult to ascertain if they represent a small underlying association or are attenuated due to misclassification error. Finally, potential confounders may have been either unmeasured or inadequately measured, for example exposure to cigarette smoke, which is a major source of indoor NO
2 and more subtle sociodemographic factors not captured by the reported socioeconomic level in the current study (for example, neighbourhood social cohesion, parental education level, and domestic violence).
In conclusion, the findings of this study contribute to the increasing evidence for association between NO
2 exposure and risk for psychosis, and are the first to our knowledge to demonstrate this association in relation to childhood PLEs. The association between NO
2 exposure and PLEs but not emotional symptoms or conduct problems raises questions about the mechanism of action of NO
2. Furthermore, the results of this study may support the need for environmental regulation of air pollution to improve childhood mental health [
4].