Amy Margolis

Bisphenol A exposure and behavioral problems among inner city children at 7-9 years of age.

BACKGROUND Bisphenol A (BPA) is a ubiquitous endocrine disrupting compound. Several experimental and epidemiological studies suggest that gestational BPA exposure can lead to neurodevelopmental and behavioral problems in early-life, but results have been inconsistent. We previously reported that prenatal BPA exposure may affect child behavior and differently among boys and girls at ages 3-5 years. OBJECTIVES We investigated the association of prenatal and early childhood BPA exposure with behavioral outcomes in 7-9 year old minority children and hypothesized that we would observe the same sex-specific pattern observed at earlier ages. METHODS African-American and Dominican women enrolled in an inner-city prospective cohort study and their children were followed from mothers pregnancy through childrens age 7-9 years. Women during the third trimester of pregnancy and children at ages 3 and 5 years provided spot urine samples. BPA exposure was categorized by tertiles of BPA urinary concentrations. The Child Behavioral Checklist (CBCL) was administered at ages 7 and 9 to assess multiple child behavior domains. Associations between behavior and prenatal (maternal) BPA concentrations and behavior and postnatal (child) BPA concentration were assessed via Poisson regression in models stratified by sex. These models accounted for potential confounders including prenatal or postnatal urinary BPA concentrations, child age at CBCL assessment, ethnicity, gestational age, maternal intelligence, maternal education and demoralization, quality of childs home environment, prenatal environmental tobacco smoke exposure, and prenatal mono-n-butyl phthalate concentration. RESULTS The direction of the associations differed between boys and girls. Among boys (n=115), high prenatal BPA concentration (upper tertile vs. lower two tertiles) was associated with increased internalizing (β=0.41, p<0.0001) and externalizing composite scores (β=0.40, p<0.0001) and with their corresponding individual syndrome scales. There was a general decrease in scores among girls that was significant for the internalizing composite score (β=-0.17, p=0.04) (n=135). After accounting for possible selection bias, the results remained consistent for boys. Conversely, high postnatal BPA concentration was associated with increased behaviors on both the internalizing composite (β=0.30, p=0.0002) and externalizing composite scores (β=0.33, p<0.0001) and individual subscores in girls but fewer symptoms in boys. These results remained significant in girls after accounting for selection bias. CONCLUSION These results suggest BPA exposure may affect childhood behavioral outcomes in a sex-specific manner and differently depending on timing of exposure.

Early-Life Exposure to Polycyclic Aromatic Hydrocarbons and ADHD Behavior Problems

Importance Polycyclic aromatic hydrocarbons are widespread urban air pollutants from combustion of fossil fuel and other organic material shown previously to be neurotoxic. Objective In a prospective cohort study, we evaluated the relationship between Attention Deficit Hyperactivity Disorder behavior problems and prenatal polycyclic aromatic hydrocarbon exposure, adjusting for postnatal exposure. Materials and Methods Children of nonsmoking African-American and Dominican women in New York City were followed from in utero to 9 years. Prenatal polycyclic aromatic hydrocarbon exposure was estimated by levels of polycyclic aromatic hydrocarbon- DNA adducts in maternal and cord blood collected at delivery. Postnatal exposure was estimated by the concentration of urinary polycyclic aromatic hydrocarbon metabolites at ages 3 or 5. Attention Deficit Hyperactivity Disorder behavior problems were assessed using the Child Behavior Checklist and the Conners Parent Rating Scale- Revised. Results High prenatal adduct exposure, measured by elevated maternal adducts was significantly associated with all Conners Parent Rating Scale-Revised subscales when the raw scores were analyzed continuously (N = 233). After dichotomizing at the threshold for moderately to markedly atypical symptoms, high maternal adducts were significantly associated with the Conners Parent Rating Scale-Revised DSM-IV Inattentive (OR = 5.06, 95% CI [1.43, 17.93]) and DSM-IV Total (OR = 3.37, 95% CI [1.10, 10.34]) subscales. High maternal adducts were positivity associated with the DSM-oriented Attention Deficit/Hyperactivity Problems scale on the Child Behavior Checklist, albeit not significant. In the smaller sample with cord adducts, the associations between outcomes and high cord adduct exposure were not statistically significant (N = 162). Conclusion The results suggest that exposure to polycyclic aromatic hydrocarbons encountered in New York City air may play a role in childhood Attention Deficit Hyperactivity Disorder behavior problems.

Interhemispheric connectivity and executive functioning in adults with Tourette syndrome.

The prefrontal cortex (PFC) is relatively smaller, and the corpus callosum (CC) larger, in adults with Tourette syndrome (TS). The authors explored the possible roles of the PFC and the CC in mediating interhemispheric interference and coordination in TS adults. They measured performance on M. Kinsbourne and J. Cooks (1971) verbal-manual interference task and on the bimanual Purdue Pegboard in 38 adults with TS and 34 healthy adults. Compared with controls, TS subjects were impaired on the bimanual Purdue Pegboard. On the dual task, right-hand performance did not differ between groups, but the normally expected left-hand advantage (opposite hemisphere condition) was absent in TS subjects. In the control group only, better left-hand performance accompanied larger PFC volumes but not CC cross-sectional area. PFC dysfunction might have precluded executive control of interference in the TS group.

Research Review: Environmental exposures, neurodevelopment, and child mental health - new paradigms for the study of brain and behavioral effects.

BACKGROUND Environmental exposures play a critical role in the genesis of some child mental health problems. METHODS We open with a discussion of childrens vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and cooccurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention-deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function. FINDINGS We consider the impact of two important exposures on childrens mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle subclinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice. CONCLUSIONS Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment, and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value.

Using IQ Discrepancy Scores To Examine the Neural Correlates of Specific Cognitive Abilities

The underlying neural determinants of general intelligence have been studied intensively, and seem to derive from the anatomical and functional characteristics of a frontoparietal network. Little is known, however, about the underlying neural correlates of domain-specific cognitive abilities, the other factors hypothesized to explain individual performance on intelligence tests. Previous preliminary studies have suggested that spatially distinct neural structures do not support domain-specific cognitive abilities. To test whether differences between abilities that affect performance on verbal and performance tasks derive instead from the morphological features of a single anatomical network, we assessed in two independent samples of healthy human participants (N = 83 and N = 58; age range, 5–57 years) the correlation of cortical thickness with the magnitude of the verbal intelligence quotient (VIQ)-performance intelligence quotient (PIQ) discrepancy. We operationalized the VIQ-PIQ discrepancy by regressing VIQ onto PIQ (VIQ-regressed-on-PIQ score), and by regressing PIQ onto VIQ (PIQ-regressed-on-VIQ score). In both samples, a progressively thinner cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) VIQ-regressed-on-PIQ scores. A progressively thicker cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) PIQ-regressed-on-VIQ scores. Variation in cortical thickness in these regions accounted for a large portion of the overall variance in magnitude of the VIQ-PIQ discrepancy. The degree of hemispheric asymmetry in cortical thickness accounted for a much smaller but statistically significant portion of variance in VIQ-PIQ discrepancy.

A Systems View of Mother-Infant Face-to-Face Communication.

Principles of a dynamic, dyadic systems view of mother-infant face-to-face communication, which considers self- and interactive processes in relation to one another, were tested. The process of interaction across time in a large low-risk community sample at infant age 4 months was examined. Split-screen videotape was coded on a 1-s time base for communication modalities of attention, affect, orientation, touch, and composite facial-visual engagement. Time-series approaches generated self- and interactive contingency estimates in each modality. Evidence supporting the following principles was obtained: (a) Significant moment-to-moment predictability within each partner (self-contingency) and between the partners (interactive contingency) characterizes mother-infant communication. (b) Interactive contingency is organized by a bidirectional, but asymmetrical, process: Maternal contingent coordination with infant is higher than infant contingent coordination with mother. (c) Self-contingency organizes communication to a far greater extent than interactive contingency. (d) Self- and interactive contingency processes are not separate; each affects the other in communication modalities of facial affect, facial-visual engagement, and orientation. Each persons self-organization exists in a dynamic, homoeostatic (negative feedback) balance with the degree to which the person coordinates with the partner. For example, those individuals who are less facially stable are likely to coordinate more strongly with the partners facial affect and vice versa. Our findings support the concept that the dyad is a fundamental unit of analysis in the investigation of early interaction. Moreover, an individuals self-contingency is influenced by the way the individual coordinates with the partner. Our results imply that it is not appropriate to conceptualize interactive processes without simultaneously accounting for dynamically interrelated self-organizing processes.

Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10–12 years of age

BACKGROUND Experimental and epidemiological studies suggest that gestational exposure to Bisphenol A (BPA), an ubiquitous endocrine disrupting chemical, may lead to neurobehavioral problems in childhood; however, not all results have been consistent. We previously reported a positive association between prenatal BPA exposure and symptoms of anxiety/depression reported by the mother at child age 7-9 years in boys, but not girls. OBJECTIVES Here, in the same birth cohort, we investigated the association of prenatal BPA exposure with symptoms of depression and anxiety self-reported by the 10-12 year olds, hypothesizing that we would observe sex-specific differences in anxiety and depressive symptoms. METHODS African-American and Dominican women living in Northern Manhattan and their children were followed from mothers pregnancy through childrens age 10-12 years. BPA was quantified in maternal urine collected during the third trimester of pregnancy and in child urine collected at ages 3 and 5 years. Children were evaluated using the Revised Childrens Manifest Anxiety Scale (RCMAS) and Childrens Depression Rating Scale (CDRS). We compared the children in the highest tertile of BPA concentration to those in the lower two tertiles. Associations between behavior and prenatal (maternal) BPA concentration or postnatal (child) BPA concentration were assessed in regression models stratified by sex. RESULTS Significant positive associations between prenatal BPA and symptoms of depression and anxiety were observed among boys. Postnatal BPA exposure was not significantly associated with outcomes. There was substantial co-occurrence of anxiety and depressive symptoms in this sample. CONCLUSION These results provide evidence that prenatal BPA exposure is associated with more symptoms of anxiety and depression in boys but not in girls at age 10-12 years.

Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems

Importance Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by‐products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress. Objective In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems. Materials and Methods We enrolled nonsmoking African‐American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH‐DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self‐reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale‐ Revised. Analyses adjusted for relevant covariates. Results Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period (“persistent” hardship or “any” hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM‐IV Inattentive (p = 0.006), DSM‐IV Hyperactive Impulsive problems (p = 0.033), and DSM‐IV Index Total (p = 0.009). Conclusion The present findings add to existing evidence that co‐exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children. HighlightsPAH are common carcinogenic and neurotoxic combustion‐related air pollutants.Exposure to PAH tends to be disproportionately high in low income communities.Prenatal PAH exposure was measured by PAH‐DNA adducts in maternal blood.We evaluated the combined effects of prenatal PAH and material hardship on ADHD.We observed significant effects of combined exposures on ADHD behavior problems.

An open resource for transdiagnostic research in pediatric mental health and learning disorders

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5–21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).

Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment.

Purpose of review The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. Recent findings Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. Summary MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.