EARLY LIFE EXPOSURES AND DEVELOPMENT OF ADHD IN CHILDHOOD

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders that imposes an enormous cost to individual, family and society across lifespan and generations in the U.S. This dissertation sought to systematically examine three potentially important early life factors in relation to ADHD, specifically, maternal cholesterol levels, early childhood lead exposure, and maternal acetaminophen use, using the data of mother-infant pairs already enrolled and followed in the Boston Birth Cohort (BBC), a high risk, predominantly urban low income minority population. First, I investigated the prospective association of maternal cholesterol levels measured within a few days of delivery with the risk of offspring ADHD diagnosis among 1479 mother-infant pairs of the BBC. A low maternal high-density lipoprotein level (≤60 mg/dL) was associated with an increased risk of ADHD. A “J” shaped relationship was observed between triglycerides and ADHD risk. These associations were more pronounced among boys. Second, I investigated the prospective associations between early childhood lead exposure and ADHD diagnosis and its potential effect modifiers among 1479 mother-infant pairs in the BBC. I found that the elevated lead levels (5-10µg/dL) in early childhood was associated with a 66% increased risk of ADHD. Boys were more vulnerable than girls at a given lead level. This risk of ADHD was reduced by half if the mother had adequate high-density lipoprotein level or low stress. Third, I examined the prospective association between maternal plasma biomarkers of acetaminophen intake measured within a few days of delivery and offspring ADHD diagnosis among 1180 mother-infant pairs of the BBC. There were significant dose-response associations between ADHD diagnosis and each maternal acetaminophen biomarker; and such associations were specific to ADHD, rather than other neurodevelopmental disorders. These findings not only raise a new mechanistic perspective for understanding the origins of ADHD but also shed new light on the sex difference in ADHD and point to opportunities for early risk assessment and primary prevention of ADHD

A Markov Process Inspired Cellular Automata Model of Road Traffic

To provide a more accurate description of the driving behaviors in vehicle queues, a namely Markov-Gap cellular automata model is proposed in this paper. It views the variation of the gap between two consequent vehicles as a Markov process whose stationary distribution corresponds to the observed distribution of practical gaps. The multiformity of this Markov process provides the model enough flexibility to describe various driving behaviors. Two examples are given to show how to specialize it for different scenarios: usually mentioned flows on freeways and start-up flows at signalized intersections. The agreement between the empirical observations and the simulation results suggests the soundness of this new approach.Comment: revised according to the helpful comments from the anonymous reviewer

Operational flexibility of active distribution networks: definition, quantified calculation and application

With a high penetration of intermittent distributed generators (DGs), the uncertainties in active distribution networks (ADNs) are exacerbated and further coupled in the networks. It brings enormous challenges on system operation and puts forward a higher requirement for the operational flexibility of ADNs. However, due to the secure constraints and diverse operational requirements, the controllability of controllable resources (CRs) cannot fully facilitate the flexible operation of ADNs. Operational flexibility is seen as a link between diverse operational requirements and flexible adjustment capabilities of CRs, which also represents the ability of the network to deploy its CRs to respond to the change of operation states. Under the framework of operational flexibility, multiple types of operational optimization problems can be reinterpreted, which provides a new perspective for the operation of ADNs. In this paper, the definition and region-based mathematical formulation of operational flexibility for ADNs are proposed firstly. Then the quantified calculation method of operational flexibility is proposed to represent flexibility provision (FP) and flexibility availability (FA). The application of operational flexibility is analyzed from the perspective of diverse operation and improvement of flexibility. Finally, case studies are performed on the modified IEEE 33-node system to show the effectiveness of the proposed method

Effect of Genotype and Maternal Affective Disorder on Intronic Methylation of FK506 Binding Protein 5 in Cord Blood DNA

A single nucleotide polymorphism (SNP: rs1360780) in FKBP5 (FK506 Binding Protein 5) has been shown to interact with exposure to childhood adversity to promote loss of methylation and increase in gene expression in adults. We asked whether rs1360780 can influence FKBP5 intronic methylation in the context of exposure to maternal affective disorders in utero. Sixty cord blood DNA samples from the Boston Birth Cohort were genotyped at rs1360780 and studied for methylation changes as they relate to genotype and exposure to affective disorders during pregnancy. Linear regression was employed to contrast the risk (TT) genotype to the heterozygous (CT) and homozygous (CC) genotypes with adjustment for potential confounders. The recessive genotype (TT) was associated with increased methylation at multiple CpGs in the FKBP5 intron 5 region (p < 0.01). These findings were enhanced among cases exposed to maternal affective disorders (p = 0.02). A human cell line treated with cortisol showed that changes in intron 5 CpG methylation and FKBP5 expression were inversely associated. These findings suggest that rs1360780 can influence FKBP5 intronic methylation by acting in cis as a methylation quantitative locus and highlight the impact of genotypic risk on methylation in utero. Additionally, prenatal stress exposure compounded with the risk genotype may lead to a compensatory increase in methylation

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.HSN268200782096CHHSN268201200008I20-FY02-56, #21-FY07-605R21ES011666R21HD0664712R01HD041702101-2314-B-400-009-MY2103-2314-B-400-004-MY32016YFC02065079164320121477087NICHD R24HD04285

The Epidemiological Characteristics of Stroke in Hunan Province, China

Previous studies have shown that Hunan Province has a high incidence of stroke and a high proportion of intracerebral hemorrhage (ICH). Considering the changes over the past three decades, little is known about the current epidemiological characteristics of stroke in Hunan Province. In 2013, a cross-sectional study was conducted at seven national disease surveillance points (DSPs) in Hunan Province. A multistage cluster sampling method was used to select a representative sample. A total of 21,156 participants aged 20 years and older were examined. Among the 21,156 participants, the number of prevalent strokes, incident strokes and deaths was 307, 87, and 36, respectively. The 2010 China census-standardized prevalence, incidence and mortality were 1191.0 per 100,000 people [95% confidence interval (CI) 1044.8–1337.2], 333.6 per 100,000 person-years (95% CI 255.7–411.5) and 129.7 per 100,000 person-years (95% CI 81.1–178.3), respectively. Ischemic stroke (IS), ICH, subarachnoid hemorrhage (SAH), and stroke of undetermined type (UND) constituted 50.6, 41.4, 5.7, and 2.3% of all incident stroke cases, respectively. Tianxin, Liuyang, Wuling, and Hongjiang have high proportions of ICH (61.5, 58.3, 60, and 50%, respectively). Hypertension is the most common risk factor for prevalent stroke (71.34%), followed by smoking (30.62%) and alcohol use (25.73%). In conclusion, Hunan Province has an extremely heavy stroke burden. The high proportion of ICH is not limited to the Changsha community; it represents an important issue for all of Hunan Province

Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder

Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1–3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose–responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted

Data_Sheet_1_The association between electronic cigarettes, sleep duration, and the adverse cardiovascular outcomes: Findings from behavioral risk factor surveillance system, 2020.docx

The joint effect of electronic cigarette smoking and insufficient sleep duration on cardiovascular disease (CVD) was unclear. This cross-sectional study aimed to evaluate the association between electronic cigarettes, sleep duration, and risk of CVD among American adults. The participants who completed the survey from the behavioral risk factor surveillance system in 2020 were included in this study. The status of electronic cigarette smoking was divided into never, former, and current use. The duration of sleep was categorized into insufficient (9 h) groups. The CVD group was defined as a patient having any of the following conditions: heart attack, coronary heart disease, or stroke according to self-report. The multivariate logistic regression model was adopted to determine the association between electronic cigarettes, sleep duration, and the risk of CVD. Sensitivity analyses were performed to assess the joint effects on the risk of CVD subtypes, including heart attack, coronary heart disease, and strokes, respectively. Subgroup analyses were performed to estimate the joint effects within the stratum of the age group. The total number of participants included in the present study was 253,561. Of which, 22,908 patients had CVD. In total, 61,293 participants had previously or currently used electronic cigarettes and 37,429 participants had inappropriate sleep duration. Former electronic cigarette users had a 10.8% increased risk of having CVD (OR = 1.108, 95% CI: 1.001–1.227) compared to users who never had electronic cigarettes. Insufficient and excessive sleep durations are associated with increased risks of CVD (OR = 1.592, 95% CI: 1.460–1.735; OR = 1.523, 95% CI: 1.320–1.758). The participants with current vaping status and lack of sleep had a 159.6% increased risk of CVD (OR = 2.596, 95% CI: 1.810–3.723). Sensitivity analyses found similar joint effects of current vaping and insufficient sleep on the risk of heart attack, coronary heart attack, and stroke. The subgroup analyses across each age stratum found that the middle-aged group is most vulnerable to the joint effect of current vaping and insufficient sleep. This study found that both current vaping and inappropriate sleep duration were associated with CVD. Additionally, there was a significant joint effect of current vaping and insufficient sleep on the risk of CVD, especially for middle-aged participants.</p

Maternal psychosocial stress and children’s ADHD diagnosis: a prospective birth cohort study

Objective: Examine the association of mothers’ psychosocial stressors before and during pregnancy with their children’s diagnosis of attention deficit hyperactivity disorder (ADHD). Methods: This study included 2140 mother–child pairs who had at least one postnatal pediatric visit at the Boston Medical Center between 2003 and 2015. Child ADHD was determined via International Classification of Diseases, Ninth Revision (ICD-9) codes documented in electronic medical records. Latent factors of maternal stress and social support and measures of the physical home environment and psychosocial adversities were constructed using exploratory factor analysis. The association between the latent factors and child ADHD diagnosis was examined using multiple logistic regression, controlling for known risk factors for ADHD. Results: Children were 1.45 (95% CI: 1.06, 1.99) and 3.03 (95% CI: 2.19, 4.20) times more likely to receive an ADHD diagnosis if their mother experienced a major stressful event during pregnancy or reported a high level of perceived stress, respectively. The number of family adversities increases the risk of ADHD diagnosis [second quartile: OR = 1.90; CI (1.31, 2.77); third quartile: OR = 1.96 CI (1.34, 2.88); fourth quartile: OR = 2.89 CI (2.01, 4.16)] compared to first quartile. Conclusions: In this prospective, predominantly urban, low-income, minority birth cohort, mothers’ psychosocial stress before and during pregnancy appears to be an independent risk factor for the development of ADHD in their children