Association of Air Pollution Exposure in Childhood and Adolescence With Psychopathology at the Transition to Adulthood

Key Points Question Is exposure to outdoor air pollution in childhood and adolescence associated with the development of psychopathology at the transition to adulthood? Findings In this cohort study of 2039 UK-born children followed up for 2 decades, early-life exposure to nitrogen oxides was significantly associated with general psychopathology at 18 years of age, representing greater internalizing, externalizing, and thought disorder symptoms. The associations were not attributable to individual or family-level factors or to disadvantageous neighborhood characteristics. Meaning These findings suggest that exposure to nitrogen oxides in early life may be a nonspecific risk factor for the development of psychopathology as young people begin the transition to adulthood.

.013 Note. CI = confidence interval. NOx = a regulated gaseous pollutant composed of nitric oxide and nitrogen dioxide. PM2.5 = a regulated aerosol pollutant with suspended solid and liquid particles smaller than 2.5 microns in diameter. All associations report the "fully adjusted" model adjusting for sex, family socioeconomic status, family psychiatric history, participant history of emotional and behavioral problems, and tobacco smoking. Beta coefficients represent unit change in psychopathology factor scores when moving from the bottom three quartiles of air pollutant exposure to the top quartile. Psychopathology factors were standardized to mean(SD)=100 (15). The non-independence of children within families was accounted for in all models by adjusting the standard errors.  .002 Note. CI = confidence interval. NOx = a regulated gaseous pollutant composed of nitric oxide and nitrogen dioxide. All associations adjusted for sex, family socioeconomic status, family psychiatric history, participant history of emotional and behavioral problems, and tobacco smoking. Beta coefficients represent unit change in psychopathology factor scores per interquartile range increment increase in NOx. Psychopathology factors were standardized to mean(SD)=100 (15). The non-independence of children within families was accounted for in all models by adjusting the standard errors. Table presents analyses conducted under a subset of participants with full air pollution, psychopathology, and neighborhood data (N=1986, 97.4% of full-study analytic sample). eAppendix 1. Additional details on the E-Risk Study sample.

Participants are members of the Environmental-Risk (E-Risk) Longitudinal Twin
Study, a nationally representative sample of children born in 1994 and 1995 in England and Wales (N=2,232). Briefly, the E-Risk sample was constructed in 1999-2000, when 1116 families with same-sex 5-year-old twins (93% of those eligible) participated in home-visit assessments. The full sample comprised 56% monozygotic (MZ) and 44% dizygotic (DZ) twin pairs; sex was evenly distributed within zygosity (49% male).
Families were recruited to represent the UK population of families with newborns in the 1990s, based on residential location throughout England and Wales and mothers' age (teenaged mothers with twins were over-selected to replace high-risk families who were selectively lost to the register through non-response. Older mothers having twins via assisted reproduction were under-selected to avoid an excess of well-educated older mothers). The cohort's neighborhoods represent the full range of socioeconomic conditions in Great Britain, as reflected in the families' distribution on a neighborhoodlevel socioeconomic index (ACORN [A Classification of Residential Neighborhoods], developed by CACI Inc. for commercial use). 1 E-Risk families' ACORN distribution closely matches that of households nation-wide: 25.6% of E-Risk families live in "wealthy achiever" neighborhoods compared to 25.3% nationwide; 5.3% vs. 11.6% live in "urban prosperity" neighborhoods; 29.6% vs. 26.9% live in "comfortably off" neighborhoods; 13.4% vs. 13.9% live in "moderate means" neighborhoods; and 26.1% vs. 20.7% live in "hard-pressed" neighborhoods. E-Risk underrepresents "urban prosperity" neighborhoods because such households are likely to be childless. Figure S1 shows E-Risk families' addresses are a near-perfect match to the deciles of the UK government's 2015 Lower-layer Super Output Area (LSOA) Index of Multiple Deprivation, which ranks British neighborhoods in terms of relative deprivation at an area level of approximately 1,500 residents; approximately 10% of the E-Risk cohort fills each of the Index's 10% bands, indicating that the E-Risk cohort accurately represents the distribution of deprivation in the UK.
Follow-up home visits were conducted when the participants were aged 7 (98% participation), 10 (96%), 12 (96%), and, most recently, 18 (93%) years. Home visits at ages 5, 7, 10, and 12 years included assessments with participants as well as their mother (or primary caretaker); the home visit at age 18 included structured interviews only with the participants. Each twin participant was assessed by a different interviewer. The average age of the twins at the time of the age-18 assessment was 18.4 years (SD = 0.36); all structured interviews were conducted after the 18 th birthday. There were no differences between those who did and did not take part at age 18 in terms of age

Ground-based evaluation of the ambient air pollution measures
Air pollution exposure was modeled at the local-scale using the US-Environmental Protection Agency's regional chemical-transport model, the Community Multiscale Air Quality Modeling (CMAQ), 3 11 Thought disorder symptoms were assessed in two ways: first, participants were asked 7 items about delusions and hallucinations (psychotic-like experiences: e.g., "Have other people ever read your thoughts?"; "Have you ever thought you were being followed or spied on?"; "Have you ever heard voices that other people cannot hear?"). 12 Second, participants were asked 6 items about unusual thoughts and feelings (prodromal symptoms: e.g., "My thinking is unusual or frightening"; "People or places I know seem different"), drawing on item pools since formalized in prodromal psychosis instruments, including the PRIME-screen and SIPS. 13 The structure of psychopathology Using confirmatory factor analysis, two standard models 14,15 that are frequently used to examine hierarchically structured constructs were estimated: a correlated-factors model with three factors (representing Internalizing, Externalizing, and Thought Disorder symptoms) and a bi-factor model specifying a General Psychopathology factor ( Figure   S3) in addition to the three specific factors. Decisions about symptom-factor loadings were guided by the Hierarchical Taxonomy of Psychopathology consortium (https://medicine.stonybrookmedicine.edu/HITOP/AboutHiTOP). 16   Covariates in the fully adjusted model included biological sex at birth and: Family socioeconomic status, measured via a composite of parental income, education, and occupation measured when participants were age 5. The three SES indicators were highly correlated (r's ranged from .57 to .67, P-value's <.05) and loaded significantly onto one latent factor (factor loadings=0.80, 0.70, and 0.83 for income, education, and occupation, respectively). The latent variable was categorized into tertiles (i.e., low-, medium-, and high-SES). 18 Family psychiatric history, assessed at the age-12 assessment from reports by biological mothers conducted as part of a family history interview. 19 Family history of psychiatric disorder was defined as a report of treatment or hospitalization for a psychiatric disorder or substance-use problem, or attempted or completed suicide for any of the child's biological mother, father, grandparents, or aunts and uncles. This was converted to the proportion of family members with a history of any psychiatric disorder (coded 0-1.0; cohort mean(SD)=0.37(0.27)).
Participant history of emotional and behavioral problems in early childhood (age 5). Emotional and behavioral problems at age 5 were assessed using the Child Behavior Checklist in interviews with mothers and the Teacher Report Form by mail for teachers. 20,21 The emotional (internalizing) problems scale is the sum of items in the withdrawn and anxious/depressed subscales, and the behavioral (externalizing) problems scale is the sum of items from the aggressive and delinquent behavior subscales. We summed and standardized mothers' and teachers' reports of each of these measures to create cross-informant scales representing total emotional and behavioral problems. Dilapidation was measured from resident ratings of problems in their neighborhood (e.g. litter, vandalized public spaces, vacant storefronts) and independent raters' assessments of these same problems based on the "virtual walk-through" using Google Street View. Disconnection was measured from resident ratings assessing neighborhood collective efficacy and social connectedness. Neighborhood collective efficacy was assessed via the resident survey using a previously validated 10-item measure of social control and social cohesion. 23 Residents were asked about the likelihood that their neighbors could be counted on to intervene in various ways if, for example: "children were skipping school and hanging out on a street corner", "children were spray-painting graffiti on a local building." They were also asked how strongly they agreed that, for example: "people around here are willing to help their neighbors", "this is a close-knit neighborhood" (item responses: 0-4). Social connectedness was assessed based on indicators of intergenerational closeness ("If any of your neighbors' children did anything that upset you would you feel that you could speak to their parents about it?"), reciprocated exchange (e.g., "Would you be happy to leave your keys with a neighbor if you went away on holiday?"), and friendship ties (e.g., "Do you have any close friends that live in your neighborhood") among neighbors. 24 Dangerousness was measured from police records of crime incidence, from neighborhood residents' ratings of how much they feared for their safety and whether they had been victimized, and from independent raters' assessments of neighborhood safety based on the "virtual walk-through" using Google Street View. Environment Deprivation), and combined with appropriate weights to calculate the Index of Multiple Deprivation (IMD). Households were assigned a neighborhood IMD based on street address at the time of the age-5, age-7, age-10, and age-12 inhome visits using scores from the 2015 IMD. We analyzed the average IMD value across these four measurements.
2. Official Crime Data. We measured local area crime by mapping a 1-mile radius around each E-Risk Study family's home and tallying the total number of crimes that occurred in the area each month in 2011, when the participants were aged 17. Streetlevel crime data, including information on the type of crime, date of occurrence, and approximate location, were accessed online as part of an open data sharing effort about crime and policing in England and Wales (https://data.police.uk/) and geocoded to the home address of the Study members. An Application Program Interface was used to extract street-level crime data for each of the geospatial coordinates marking