Project description:Low socioeconomic status (SES) is associated with greater risk for symptoms of attention-deficit/hyperactivity disorder (ADHD). One mechanism through which SES may confer risk for ADHD is by influencing brain structure. Alterations to cortical thickness, surface area and subcortical volume have been associated with low SES and with the presence of ADHD across multiple studies. The current study examined whether cortical thickness, surface area or subcortical volume mediate the associations between SES and ADHD in youth 3-21 years old (N = 874) from the Pediatric Imaging, Neurocognition and Genetics Study. Freesurfer was used to estimate cortical thickness, surface area and subcortical volume from structural magnetic resonance imaging. Parents reported on demographics, family SES, ADHD diagnoses and the presence of child attention problems. Statistical mediation was assessed using a bootstrap resampling procedure. Controlling for parental ADHD, child age, gender, birth weight and scanner, children in low SES families were more likely to be in the ADHD group. Consistent with previous reports in this sample, low SES was associated with reduced surface area across the frontal lobe and reduced subcortical volume in the amygdala, cerebellum, hippocampus and basal ganglia. Of these regions, a significant indirect effect of SES on ADHD status through subcortical volume was observed for the left cerebellum (95% confidence interval: 0.004, 0.022), the right cerebellum (95% confidence interval: 0.006, 0.025), and the right caudate (95% confidence interval: 0.002, 0.022). Environmentally mediated changes in the cerebellum and the caudate may be neurodevelopmental mechanisms explaining elevated risk of ADHD in children in low SES families.
Project description:Human epidemiological and animal-model studies suggest that separate exposure to stress or serotonin-selective reuptake inhibitor (SSRI) antidepressants during pregnancy increases risks for neurodevelopmental disorders in offspring. Yet, little is known about the combined effects of maternal stress and SSRIs with regard to brain development in utero. We found that the placenta is highly permeable to the commonly prescribed SSRI (±)-citalopram (CIT) in humans and mice, allowing rapid exposure of the fetal brain to this drug. We investigated the effects of maternal chronic unpredictable stress in mice with or without maternal oral administration of CIT from embryonic day (E)8 to E17. We assessed fetal brain development using magnetic resonance imaging and quantified changes in serotonergic, thalamocortical, and cortical development. In utero exposure to maternal stress did not affect overall fetal brain growth. However, serotonin tissue content in the fetal forebrain was increased in association with maternal stress; this increase was reversed by maternal CIT. In utero exposure to stress increased the numbers of deep-layer neurons in specific cortical regions, whereas CIT increased overall cell numbers without changing the proportions of layer-specific neurons to offset the effects of stress on deep-layer cortical development. These findings suggest that stress and SSRI exposure in utero differentially impact serotonin-dependent fetal neurodevelopment such that CIT reverses key effects of maternal gestational stress on offspring brain development.
Project description:ImportanceSome studies based on proportions of patients with perforated appendicitis (PA) among all patients with acute appendicitis (AA) have found an association between socioeconomic status (SES) and risk of perforation. A potential limitation is their use of proportions, which assumes that incidence of AA is evenly distributed across populations at risk. This assumption may be invalid, and SES may have a more complex association with both AA and PA.ObjectiveTo generate population-based incidences of AA and PA and to examine geographic patterns of incidence alongside geographic patterns of SES.Design, setting, and participantsRetrospective study of data from Washington's Comprehensive Hospital Abstract Reporting System and the 2010 US census. Geographic methods were used to identify patterns of age- and sex-standardized incidence in Washington State between 2008 and 2012. The study included all patients discharged with International Classification of Diseases, Ninth Revision codes for AA or PA. Data were analyzed between November 2016 and December 2018.ExposuresLocation of primary residence.Main outcomes and measuresAge- and sex-standardized incidence for AA and PA was generated for each census tract (CT). Global spatial autocorrelation was examined using Moran index (0.0?=?completely random incidence; 1.0?=?fully dependent on location). Clusters of low-incidence CTs (cold spots) and high-incidence CTs (hot spots) were identified for AA. Census-based SES data were aggregated for hot spots and cold spots and then compared.ResultsStatewide, over the 5-year study period, there were 35?730 patients with AA (including 9780 cases of PA), of whom 16?574 were women (46.4%). Median age of the cohort was 29 years (IQR, 16-48 years). Statewide incidence of AA and PA was 106 and 29 per 100?000 person-years (PY), respectively. Crude incidence was higher within the male population and peaked at age 10 to 19 years. Age- and sex-standardized incidence of AA demonstrated significant positive spatial autocorrelation (Moran index, 0.30; P?<?.001), but autocorrelation for PA was only half as strong (0.16; P?<?.001). Median incidence of AA was 118.1 per 100?000 PY among hot spots vs 86.2 per 100?000 PY among cold spots (P?<?.001). Socioeconomic status was higher in cold spots vs hot spots: mean proportion of college-educated adults was 56% vs 26% (P?<?.001), and mean per capita income was $44?691 vs $30?027 (P?<?.001).Conclusions and relevanceAge- and sex-standardized incidence of appendicitis is not randomly distributed across geographic subunits, and geographic clustering of AA is twice as strong as PA. Socioeconomic advantages, such as higher income and secondary education, are strongly associated with lower incidence of AA. These findings challenge conventional views that AA occurs randomly and has no predisposing characteristics beyond age/sex. Socioeconomic status, and likely other geographically circumscribed factors, are associated with incidence of AA.
Project description:The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid were collected from women who had undergone amniocentesis early in the 2nd trimester. All pregnancies were followed up until delivery and fetal growth patterns and birth weights were recorded, following which pregnancies were divided into three groups based on fetal weight: (1) AGA (appropriate for gestational age), (2) SGA (small for gestational age), and (3) LGA (large for gestational age). We focused on these three groups representing a reflection of the intrauterine growth spectrum. Our results revealed the presence of notably higher BDNF levels in the amniotic fluid of impaired growth fetuses by comparison with those of normal growth. Both SGA and macrosomic fetuses are characterized by notably higher amniotic fluid levels of BDNF (mean values of 36,300?pg/ml and 35,700?pg/ml, respectively) compared to normal-growth fetuses (mean value of 32,700?pg/ml). Though apparently small, this difference is, nevertheless, statistically significant (p value?<?0.05) in SGA fetuses in the extremes of the distribution, i.e., below the 3rd centile. In conclusion, there is clear evidence that severe impairment of fetal growth induces the increased production of fetal brain growth factor as an adaptive mechanism in reaction to a hostile intrauterine environment, thereby accelerating fetal brain development and maturation.
Project description:BackgroundThe effect of socioeconomic status (SES) on hepatocellular carcinoma (HCC) is still unclear, and there is no nomogram integrated SES and clinicopathological factors to predict the prognosis of HCC. This research aims to confirm the effects of SES on predicting patients' survival and to establish a nomogram to predict the prognosis of HCC.MethodsThe data of HCC patients were collected from the Surveillance, Epidemiology, and Final Results (SEER) database from 2011 to 2015. SES (age at diagnosis, race and sex, median family income, education level, insurance status, marital status, residence, cost of living index, poverty rate) and clinicopathological factors were included in univariate and multivariate Cox regression analysis. Nomograms for predicting 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) were established and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration plot, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI).ResultsA total of 33,670 diagnosed HCC patients were involved, and nomograms consisting of 19 variables were established. The C-indexes of the nomograms are higher than TNM staging system, which predicts the CSS (0.789 vs. 0.692, p < 0.01) and OS (0.777 vs. 0.675, p < 0.01). The ROC curve, calibration diagram, IDI, and NRI showed the improved prognostic value in 1-, 3-, and 5-year survival rates.ConclusionSES plays an important role in the prognosis of HCC patients. Therefore, policymakers can make more precise and socially approved policies to improve HCC patients' CSS and OS.
Project description:Childhood socioeconomic status is robustly associated with various children's cognitive factors and neural mechanisms. Here we show the association of childhood socioeconomic status with psychometric intelligence and mean diffusivity and fractional anisotropy using diffusion tensor imaging at the baseline experiment (N = 285) and longitudinal changes in these metrics after 3.0 ± 0.3 years (N = 223) in a large sample of normal Japanese children (mean age = 11.2 ± 3.1 years). After correcting for confounding factors, cross-sectional and longitudinal analyses show that higher childhood socioeconomic status is associated with greater baseline and baseline to follow-up increase of psychometric intelligence and mean diffusivity in areas around the bilateral fusiform gyrus. These results demonstrate that higher socioeconomic status is associated with higher psychometric intelligence measures and altered microstructural properties in the fusiform gyrus which plays a key role in reading and letter recognition and further augmentation of such tendencies during development. Definitive conclusions regarding the causality of these relationships requires intervention and physiological studies. However, the current findings should be considered when developing and revising policies regarding education.
Project description:One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.
Project description:Atrazine (ATR) is a commonly used agricultural herbicide and a potential endocrine disruptor that may cause testicular dysgenesis. The objective of the present study was to investigate the effects of atrazine on fetal testis development after in utero exposure. Female Sprague-Dawley rats were gavaged daily with vehicle (corn oil, control) or atrazine (25, 50, and 100 mg/kg body weight/day) from gestational day 12 to 21. Atrazine dose-dependently decreased serum testosterone levels of male pups, with a significant difference from the control recorded at a dose of 100 mg/kg. In addition, atrazine significantly increased fetal Leydig cell aggregation at a dose of 100 mg/kg. Atrazine increased fetal Leydig cell number but not Sertoli cell number. However, atrazine down-regulated Scarb1 and Cyp17a1 in the fetal Leydig cell per se and Hsd17b3 and Dhh in the Sertoli cell per se. These results demonstrated that in utero exposure to atrazine disrupted rat fetal testis development.
Project description:ObjectiveEvaluate whether arsenic-related diabetes risks differ between people of low and high socioeconomic status (SES).MethodsWe used data collected between October 2007-December 2010 from a population-based cancer case-control study (N = 1301) in Northern Chile, an area with high arsenic water concentrations (>800 µg/L) and comprehensive records of past exposure. Information on lifetime exposure and potential confounders were obtained using structured interviews, questionnaires, and residential histories. Type 2 diabetes was defined as physician-diagnosed diabetes or oral hypoglycemic medication use. SES was measured using a 14-point scale based on ownership of household appliances, cars, internet access, or use of domestic help. Logistic regression was used to assess the relationship between arsenic and diabetes within strata of SES.ResultsAmong those with low SES, the odds ratio (OR) for diabetes comparing individuals in the highest to lowest tertile of lifetime average arsenic exposure was 2.12 (95% confidence interval (CI) 1.29-3.49, p = 0.004). However, those in the high SES group were not at increased risk (OR = 1.12 [95% CI = 0.72-1.73]).ConclusionsOur findings provide evidence that risks of arsenic-related diabetes may be higher in Chile in people with low versus high SES.
Project description:Although socioeconomic status (SES) has been associated with cancer risk, little research on this association has been done in Japan. To evaluate the association between SES and digestive tract cancer risk, we conducted a case-control study for head and neck, esophageal, stomach, and colorectal cancers in 3188 cases and the same number of age- and sex-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center III (HERPACC III). We employed the education level and areal deprivation index (ADI) as SES indicators. The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models adjusted for potential confounders. Even after allowance for known cancer risk factors, the education level showed linear inverse associations with head and neck, stomach, and colorectal cancers. Compared to those educated to junior high school, those with higher education showed statistically significantly lower risks of cancer (0.43 (95% CI: 0.27-0.68) for head and neck, 0.52 (0.38-0.69) for stomach, and 0.52 (0.38-0.71) for colorectum). Consistent with these results for the educational level, the ADI in quintiles showed positive associations with head and neck, esophageal, and stomach cancers (p-trend: p = 0.035 for head and neck, p = 0.02 for esophagus, and p = 0.013 for stomach). Interestingly, the positive association between ADI and stomach cancer risk disappeared in the additional adjustment for Helicobacter pylori infection and/or atrophic gastritis status. In conclusion, a lower SES was associated with an increased risk of digestive cancers in Japan and should be considered in cancer prevention policies for the target population.