Childhood urbanicity is associated with emotional episodic memory-related striatal function and common variation in NTRK2.

BACKGROUND: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals' choices of residence but also modulate how the living environment affects responses to episodic memory. METHODS: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. RESULTS: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10-6). These findings were confirmed in the replication sample. CONCLUSIONS: We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.

Inequity in access to digital public primary healthcare in Sweden: a cross-sectional study of the effects of urbanicity and socioeconomic status on utilization.

BACKGROUND: Social and geographical inequity in access to primary healthcare is an ongoing concern in Sweden. Digital care can potentially decrease geographical inequity. This study aimed to evaluate how urbanicity affects the utilization of a public digital primary healthcare service - PHC Online. METHODS: We performed an ecological cross-sectional study of 4,482 PHC Online visits grouped by 83 public primary healthcare centers. Multiple linear regression analysis was performed with PHC Online visits per 1,000 registered patients as the dependent variable and urbanicity (municipalities grouped by number of inhabitants), socioeconomic status (Care Need Index), and morbidity (Adjusted Clinical Groups) per primary healthcare center as independent variables. RESULTS: Utilization of PHC Online was more common among those of a younger age (median 32 years) and among women (65%). Urbanicity did not affect utilization. Lower socioeconomic status and higher morbidity had negative effects on utilization (B -3.289, p = 0.001, B -7.728, p = 0.045). CONCLUSIONS: Geographical differences based on urbanicity do not seem to affect the utilization of PHC Online. Further studies are needed to clarify a possible association to geographical barriers in access to primary healthcare, specifically accounting for factors associated with urbanicity and distance to physical clinics, and how age and sex affect such an association. Lower utilization of PHC Online in low socioeconomic status and high morbidity populations raises questions on the effect of digital primary care on equitable access to primary healthcare.

Disparities in the association between ambient temperature and preterm birth according to individual and regional characteristics: a nationwide time-stratified case-crossover study.

BACKGROUND: Several studies have reported that climate change elevates heat exposure in pregnant women and high temperatures during pregnancy are associated with preterm births (PTBs). Although the association might be disproportionate, related evidence remains sparse. We evaluated the disproportionate risk of PTB associated with ambient temperature during pregnancy by individual and regional characteristics in South Korea. METHODS: We collected data on birth certificates and daily mean temperatures during the period from 2011 to 2019. A time-stratified case-crossover design was used to investigate the association between temperature and PTB and stratified analyses were conducted to examine the effect modification of individual and regional characteristics. RESULTS: A total of 160,067 singleton PTBs were recorded in Korea from 2011 to 2019. A 5℃ increase in the mean temperature during the last four weeks before delivery was associated with an increased risk of PTB with an odds ratio (OR) of 1.03 (95% confidence interval [CI]: 1.02, 1.05), and the association was more evident in mothers aged ≥35 years (OR: 1.06 [95% CI: 1.03, 1.10]) and with low education levels (OR: 1.04 [95% CI: 1.02, 1.05]). Additionally, the estimated risk was evident in districts with lower medical resources and more prominent disparities were shown by individual and regional characteristics in rural areas than in urban areas. CONCLUSIONS: This study provides evidence that the risk of PTB related to ambient temperature is disproportionate by individual and regional characteristics and suggests the need for public health policies to alleviate the disparities, especially in rural areas.

Season of birth and schizotypy in a sample of undergraduate students.

PURPOSE: In line with the psychotic continuum theory, the study of psychometric schizotypy in non-clinical samples has been proposed as a convenient yet powerful method for studying the etiology of psychosis. Based on this paradigm, several studies explored the association between season of birth (SoB) and schizotypy but led to inconsistent results. Building on the analysis of the previous studies, in the present study, we aimed to advance our understanding by improving the methodology (using a homogeneous group, eliminating unreliable respondents, taking into account potential confounders) and the reporting. METHODS: Subjects were recruited among undergraduate students from 3 Romanian Universities. To limit the potential influence of invalid response, we applied methods for detecting unreliable and/or biased questionnaires and excluded subjects with unreliable/ biased answers from the analyses. Schizotypal dimensions were measured using the Romanian translation of the 22-items Schizotypal Personality Questionnaire-Brief (SPQ-B). The association between schizotypy scores and season of birth was explored using linear regression. RESULTS: In a sample of 484 undergraduate students from Romania, we found that being born in late winter/early spring (February and March) was associated to higher total schizotypy score and disorganization. Furthermore, we found that restricting the sample to subjects born in an urban environment increased the strength of the association. CONCLUSION: This study is consistent with an association between SoB and the risk of psychotic disorders.

Geographical variation in treated psychotic and other mental disorders in Finland by region and urbanicity.

PURPOSE: In Finland, prevalence of schizophrenia is higher in the eastern and northern regions and co-occurs with the distribution of schizophrenia polygenic risk scores. Both genetic and environmental factors have been hypothesized to contribute to this variation. We aimed to examine the prevalence of psychotic and other mental disorders by region and degree of urbanicity, and the impacts of socio-economic adjustments on these associations. METHODS: Nationwide population registers from 2011 to 2017 and healthcare registers from 1975 to 2017. We used 19 administrative and three aggregate regions based on the distribution of schizophrenia polygenic risk scores, and a seven-level urban-rural classification. Prevalence ratios (PRs) were calculated by Poisson regression models and adjusted for gender, age, and calendar year (basic adjustments), and Finnish origin, residential history, urbanicity, household income, economic activity, and physical comorbidity (additional adjustments) on an individual level. Average marginal effects were used to visualize interaction effects between region and urbanicity. RESULTS: A total of 5,898,180 individuals were observed. All mental disorders were slightly more prevalent (PR 1.03 [95% CI, 1.02-1.03]), and psychotic disorders (1.11 [1.10-1.12]) and schizophrenia (1.19 [1.17-1.21]) considerably more prevalent in eastern and northern than in western coastal regions. After the additional adjustments, however, the PRs were 0.95 (0.95-0.96), 1.00 (0.99-1.01), and 1.03 (1.02-1.04), respectively. Urban residence was associated with increased prevalence of psychotic disorders across all regions (adjusted PR 1.21 [1.20-1.22]). CONCLUSION: After adjusting for socioeconomic and sociodemographic factors, the within-country distribution of mental disorders no longer followed the traditional east-west gradient. Urban-rural differences, on the other hand, persisted after the adjustments.

Urbanicity and rates of untreated psychotic disorders in three diverse settings in the Global South.

BACKGROUND: Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad. METHODS: Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18-64 with previously untreated psychotic disorders residing in each catchment area (May 2018-April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years). RESULTS: We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68-3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51-0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93-1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area. CONCLUSIONS: This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

Urbanicity, posttraumatic stress disorder, and effect modification by socioeconomic position: A nested case-control study of the Korean National Health Insurance Database.

BACKGROUND: We aimed to estimate the association between urbanicity and the onset of posttraumatic stress disorder (PTSD) and to investigate heterogeneity therein according to age and socioeconomic position (SEP). METHODS: We analyzed administrative data from the Korean National Health Insurance Database for patients with PTSD from 2004 to 2018 (N = 109,230) and for a 1:4 sample of age-, sex-, and enrollment year-matched controls. Information on eligibility, SEP (proxied by insurance premium), place of residence, diagnosis, and medical claims was obtained. Urbanicity of administrative districts was assessed using data from the Korean Statistical Information Service, 2005-2018. We estimated hazard ratios (HRs) from baseline and time-dependent models. Subgroup analyses and polynomial splines were used to investigate heterogeneity by age and SEP. RESULTS: Urbanicity was associated with an increased risk of PTSD (per 10%p increase, HR = 1.056, 95% CI 1.050-1.061). A positive association was estimated among patients aged 0-29 years (HR = 1.115, CI 1.106-1.124), while negative associations were estimated among patients aged 30-64 years (HR = 0.990, CI 0.987-0.994) and 65 years or older (HR = 0.992, CI 0.979-1.014). The estimated associations with urbanicity were more prominent at the extremes of SEP, but only among younger participants. CONCLUSION: Urban residence was associated with an increased risk of PTSD diagnosis. The estimated association was larger among younger individuals (but not among middle-aged and older individuals). Among younger individuals, the estimated association was larger at both extremes of SEP.

Neighbourhood residential density, urbanicity and incident dementia and Alzheimer's disease: A 12-year prospective cohort study from the UK Biobank.

INTRODUCTION: An increasing proportion of global population is exposed to urban densification in an aging society. However, little is known of the role of residential density and urbanicity on the risk of developing dementia including Alzheimer's disease. We examined long-term associations between residential density and urbanicity and risks of incident dementia and Alzheimer's disease. METHODS: This prospective cohort study included participants from the UK Biobank who lived at the same residential address, had no self-reported neurological conditions and without dementia at baseline. Residential density was measured as the number of dwelling units within 1-km street neighbourhood of participant's home address. A composite index of urbanicity was developed from neighbourhood-level z-standardized densities of housing, retail, public transport and street centrality. Hazard ratios were derived from Cox proportional hazard models adjusted for known risk factors. RESULTS: The analytic sample included 239,629 participants aged 38-72 years. During a median follow-up of 12.3 years (interquartile range 11.5-13.0 years), 2,176 participants developed dementia and 1,004 Alzheimer's disease. After adjustments for potential risk factors, each 1,000 units/Km2 increment in residential density was associated with higher risks of dementia (hazard ratio [HR]=1.10, 95% confidence interval [CI]: 1.06-1.15) and Alzheimer's disease (HR=1.10, 95% CI: 1.04-1.16). Consistently, categorical models showed that living in neighbourhoods of higher residential density and urbanicity were associated with higher risks of dementia (HR = 1.30, 95% CI: 1.12-1.51 for the highest density quintile compared to the lowest and HR = 1.21, 95% CI: 1.05-1.39 for the highest urbanicity quintile relative to the lowest). The associations were more pronounced in female, age >65 years, and among participants of the low income and those being frail and having shorter leucocyte telomere length (LTL). CONCLUSIONS: Higher residential density and urbanicity was found to be positively associated with elevated risks of dementia and Alzheimer's disease. Optimizing neighbourhood residential density maybe one of the upstream considerations for mitigating against neurodegenerative diseases.

The effects of environmental factors associated with childhood urbanicity on brain structure and cognition.

Urbanization is a trend lasting for more than one century worldwide. Four hundred ninety male and female adult Chinese Han participants with different urban and rural childhoods were included in this study. Early-life urban environment was found benefit for total grey matter volume (GMV), dorsolateral prefrontal cortex (DLPFC) GMV, temporal pole (TP) GMV and cognition function, and negatively correlated with medial prefrontal cortex (MPFC) GMV. Regression analysis showed that maternal education was a protective factor for total and DLPFC GMVs, while having siblings was better for MPFC GMV. Total, DLPFC and TP GMVs acts mediation effects between childhood urbanicity and different cognitive domains. These findings may suggest some pros and cons on brain structure associated with childhood urbanicity and related environmental factors.

Food and beverage purchases at formal and informal outlets in Mexico.

OBJECTIVE: To examine food and beverage purchasing patterns across formal and informal outlets among Mexican households' and explore differences by urbanicity and income. DESIGN: Cross-sectional study of a nationally representative sample of households. We calculated the proportion of total food and beverage expenditure in each household by food outlet type overall and by urbanicity and income. We defined informal outlets as those which are not registered or regulated by tax and fiscal laws. Since some of the outlets within community food environments do not fall in clear categories, we defined a continuum from formal to informal outlets, adding mixed outlets as a category. SETTING: Mexico. PARTICIPANTS: Mexican households (n 74 203) from the 2018 National Income and Expenditure Survey. RESULTS: Of the total food and beverage purchases, outlets within the formal food sector (i.e. supermarkets and convenience stores) accounted for 15 % of the purchases, 13 % of purchases occurred in outlets within the informal food sector (i.e. street markets, street vendors and acquaintances) and 70 % in fiscally mixed outlets (i.e. small neighbourhood stores, specialty stores and public markets). Across levels of urbanicity and income, most food and beverage purchases occurred in mixed outlets. Also, purchases in informal and mixed outlets decreased as levels of urbanicity and income increased. In contrast to informal outlets, purchases in formal outlets were most likely from richer households and living in larger sized cities. CONCLUSIONS: Understanding where Mexican households shop for food is relevant to create tailored interventions according to food outlet type, accounting for regulatory and governance structures.

The synergistic interaction between urbanicity and maternal education affecting childcare pressure related to autism spectrum disorder in two national birth cohort studies.

To gain a holistic approach for parental help-seeking behavior and ASD diagnosis, this study aimed to use two national birth cohort study datasets to investigate the pathway relationship between personal and social/environmental factors, including maternal perceived childcare pressure, maternal level of education, urbanization at age 3, and the chance of receiving a autism spectrum disorder (ASD) diagnosis at when children are aged 5.5 years (2.5 years later). The 2003 Taiwan Birth Cohort Pilot Study (TBCS-p; N = 1618) and 2005 Taiwan Birth Cohort Study (TBCS; N = 19,183) datasets were used. The TBCS-p and TBCS both showed similar prevalence of ASD (0.3-0.4%). Children with ASD characteristics, as measured using the Modified Checklist of Autism in Toddlers, had 8.27-18.20 times increased likelihood of receiving ASD diagnosis [TBCS confidence interval (CF) of 5.32-12.86; TBCS-p CF of 2.03-163.46]. Pathway analysis showed that, although having a mother with higher education or who lived in a city decreased the chance for ASD diagnosis, the interactive effect of a maternal higher level of education and living in a city led to an increased likelihood for ASD diagnosis. Additionally, mothers who perceived a higher level of childcare pressure were also more likely to seek medical assistance and diagnosis. Access to healthcare (living in the city), maternal level of awareness (level of education), and perceived childcare pressure are all factors that influence help-seeking behavior and diagnosis. Therefore, medical professionals should pay special attention to the developmental condition of children in underserved backgrounds and rural areas to prevent delayed diagnosis.

Recent and lifetime maternal substance use: Rurality and economic distress.

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.

Ecological Study of Urbanicity and Self-reported Poor Mental Health Days Across US Counties.

Geography may influence mental health by inducing changes to social and physical environmental and health-related factors. This understanding is largely based on older studies from Western Europe. We sought to quantify contemporary relationships between urbanicity and self-reported poor mental health days in US counties. We performed regression on US counties (n = 3142) using data from the County Health Rankings and Roadmaps. Controlling for state, age, income, education, and race/ethnicity, large central metro counties reported 0.24 fewer average poor mental health days than small metro counties (t = - 5.78, df = 423, p < .001). Noncore counties had 0.07 more average poor mental health days than small metro counties (t = 3.06, df = 1690, p = 0.002). Better mental health in large central metro counties was partly mediated by differences in the built environment, such as better food environments. Poorer mental health in noncore counties was not mediated by considered mediators.

Built environment factors moderate pandemic fatigue in social distance during the COVID-19 pandemic: A nationwide longitudinal study in the United States.

Non-pharmaceutical interventions (NPIs) remain some of the most effective measures for coping with the ever-changing coronavirus disease 2019 (COVID-19) pandemic. Pandemic fatigue, which manifests as the declined willingness to follow the recommended protective behaviors (e.g., keeping social distance policies, wearing masks), has commanded increasing attention from researchers and policymakers after the prolonged NPIs and COVID-19 worldwide. However, long-term changes in pandemic fatigue are not well understood, especially amidst the ever-changing pandemic landscape. Built environment factors have been shown to positively affect mental and physical health, but it is still unclear whether built environments can moderate pandemic fatigue. In this study, we used Google mobility data to investigate longitudinal trends of pandemic fatigue in social distance since the onset of NPIs enforcement in the United States. The results indicated that pandemic fatigue continuously worsened over nearly two years of NPIs implementation, and a sharp increase occurred after the vaccination program began. Additionally, we detected a significant moderation effect of greenspace and urbanicity levels on pandemic fatigue. People living in areas with high levels of greenness or urbanicity experienced lower levels of pandemic fatigue. These findings not only shed new light on the effects of greenness and urbanicity on COVID-19 pandemic fatigue, but also provide evidence for developing more tailored and effective strategies to cope with pandemic fatigue.

Rural-Urban Differences in Maternal Mortality Trends in the United States, 1999-2017: Accounting for the Impact of the Pregnancy Status Checkbox.

It has been difficult to measure rural-urban differences in maternal mortality ratios (MMRs) in the United States in recent years because of the incremental adoption of a pregnancy status checkbox on the standard US death certificate. Using 1999-2017 mortality and birth data, we examined the impact of the pregnancy checkbox on MMRs according to urbanicity of residence (large urban area, medium/small urban area, or rural area), using log-binomial regression models to predict trends that would have been observed if all states had adopted the checkbox as of 1999. Implementation of the checkbox resulted in an average estimated increase of 7.5 maternal deaths per 100,000 live births (95% confidence interval (CI): 6.3, 8.8) in large urban areas (a 76% increase), 11.6 (95% CI: 9.6, 13.6) in medium/small urban areas (a 113% increase), and 16.6 (95% CI: 12.9, 20.3) in rural areas (a 107% increase), compared with MMRs prior to the checkbox. Assuming that all states had the checkbox as of 1999, demographic-factor-adjusted predicted MMRs increased in rural areas, declined in large urban areas, and did not change in medium/small urban areas. However, trends and urban-rural differences were substantially attenuated when analyses were limited to direct/specific causes of maternal death, which are probably subject to less misclassification. Accurate ascertainment of maternal deaths, particularly in rural areas, is important for reducing disparities in maternal mortality.

Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.

BACKGROUND: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. METHODS: We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. RESULTS: Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. CONCLUSION: Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

Demographic and behavioral characteristics of urban and non-urban PrEP-using MSM in the South.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention intervention; however, most studies of PrEP adherence and persistence among men who have sex with men (MSM) have been conducted with MSM who live in urban areas. The experiences of PrEP-using MSM in non-urban areas might differ due to increased barriers to culturally competent care. We examined similarities and differences among urban and non-urban PrEP-using MSM in the southern United States, the region with the highest number of annual HIV diagnoses. We surveyed a total of 78 (n = 25 non-urban, n = 53 urban) PrEP-using MSM. Self-reported adherence was high across all participants. No differences were observed with respect to PrEP persistence, source of PrEP, or reasons for PrEP initiation. Fewer non-urban than urban men reported STI testing in the past 12 months. Overall, we observed few differences comparing urban and non-urban PrEP-using MSM. Additional studies are needed to describe differences in PrEP initiation comparing urban and non-urban MSM.

DNA Methylation and Resting Brain Function Mediate the Association between Childhood Urbanicity and Better Speed of Processing.

Urbanicity has been suggested to affect cognition, but the underlying mechanism remains unknown. We examined whether epigenetic modification (DNA methylation, DNAm), and brain white matter fiber integrity (fractional anisotropy, FA) or local spontaneous brain function activity (regional homogeneity, ReHo) play roles in the association between childhood urbanicity and cognition based on 497 healthy Chinese adults. We found significant correlation between childhood urbanicity and better cognitive performance. Multiset canonical correlation analysis (mCCA) identified an intercorrelated DNAm-FA-ReHo triplet, which showed significant pairwise correlations (DNAm-FA: Bonferroni-adjusted P, Pbon = 4.99E-03, rho = 0.216; DNAm-ReHo: Pbon = 4.08E-03, rho = 0.239; ReHo-FA: Pbon = 1.68E-06, rho = 0.328). Causal mediation analysis revealed that 1) ReHo mediated 10.86% childhood urbanicity effects on the speed of processing and 2) childhood urbanicity alters ReHo through DNA methylation in the cadherin and Wnt signaling pathways (mediated effect: 48.55%). The mediation effect of increased ReHo in the superior temporal gyrus underlying urbanicity impact on a better speed of processing was further validated in an independent cohort. Our work suggests a mediation role for ReHo, particularly increased brain activity in the superior temporal gyrus, in the urbanicity-associated speed of processing.

Do temporal trends of associations between short-term exposure to fine particulate matter (PM2.5) and risk of hospitalizations differ by sub-populations and urbanicity-a study of 968 U.S. counties and the Medicare population.

While associations between short-term exposure to fine particulate matter (PM2.5) and risk of hospitalization are well documented and evidence suggests that such associations change over time, it is unclear whether these temporal changes exist in understudied less-urban areas or differ by sub-population. We analyzed daily time-series data of 968 continental U.S. counties for 2000-2016, with cause-specific hospitalization from Medicare claims and population-weighted PM2.5 concentrations originally estimated at 1km × 1 km from a hybrid model. Circulatory and respiratory hospitalizations were categorized based on primary diagnosis codes at discharge. Using modified Bayesian hierarchical modelling, we evaluated the temporal trend in association between PM2.5 and hospitalizations and whether disparities in this trend exist across individual-level characteristics (e.g., sex, age, race, and Medicaid eligibility as a proxy for socio-economic status) and urbanicity. Urbanicity was categorized into three levels by county-specific percentage of urban population based on urban rural delineation from the U.S. Census. In this cohort with understudied less-urban areas without regulatory monitors, we still found positive association between circulatory and respiratory hospitalization and short-term exposure to PM2.5, with higher effect estimates towards the end of study period. Consistent with current literature, we identified significant disparity in associations by race, socioeconomic status and urbanicity. We found that the percentage change in circulatory hospitalization rate per 10 µg/m3 increase in PM2.5 was higher in the 2008-2016 time period compared to the 2000-2007 period by 0.33% (95% posterior credible interval 0.22, 0.44%), 0.52% (0.33, 0.69%), and 0.67% (0.53, 0.83%) for low, medium and high tertiles of urban areas, respectively. We also observed significant differences in temporal trends of associations across socioeconomic status, sex, and age, indicating a possible widening in disparity of PM2.5-related health burden. This study raises the importance of considering environmental justice issues in PM2.5-related health impacts with respect to how associations may change over time.

Exposure to heat during pregnancy and preterm birth in North Carolina: Main effect and disparities by residential greenness, urbanicity, and socioeconomic status.

BACKGROUND: Although previous literature suggested that several factors may be associated with higher risk of adverse health outcomes related to heat, research is limited for birth outcomes. OBJECTIVES: We investigated associations between exposure to heat/heat waves during the last week of gestation and preterm birth (PTB) in North Carolina (NC) and evaluated effect modification by residential greenness, urbanicity, and socioeconomic status (SES). METHODS: We obtained individual-level NC birth certificate data for May-September 2003-2014. We estimated daily mean temperature at each maternal residential address using Parameter-elevation Regressions on Independent Slopes Model (PRISM) data. We created 3 definitions of heat waves (daily temperature ≥95th, 97th, 99th percentile for NC warm season temperature, for ≥2 consecutive days). Normalized Difference Vegetation Index (NDVI) was used to assess residential greenness. Community-level modifiers (e.g., income, urbanicity) were considered. We applied Cox proportional hazard models to estimate the association between exposure to heat/heat waves and PTB, controlling for covariates. Stratified analyses were conducted to evaluate whether the association between heat and PTB varied by several individual and community characteristics. RESULTS: Of the 546,441 births, 8% were preterm. Heat exposure during the last week before delivery was significantly associated with risk of PTB. The hazard ratio for a 1 °C increase in temperature during the last week before delivery was 1.01 (95% CI: 1.00, 1.02). Higher heat-PTB risk was associated with some characteristics (e.g., areas that were urbanized, low SES, or in the Coastal Plain). We also found significant PTB-heat risk in areas with low greenness for urbanized area. For heat waves, we did not find significantly positive associations with PTB. DISCUSSION: Findings provide evidence that exposure to heat during pregnancy increases risk of PTB and suggest disparities in these risks. Our results have implications for future studies of disparity in heat and birth outcomes associations.