Grantee Research Project Results
2016 Progress Report: The Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
EPA Grant Number: R836154C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R836154
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: The Columbia Center for Children’s Environmental Health
Center Director: Perera, Frederica P.
Title: The Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
Investigators: Rauh, Virginia , Herbstman, Julie Beth , Bowman, F. Dubois , Margolis, Amy E. , Tang, Deliang
Current Investigators: Rauh, Virginia
Institution: Columbia University in the City of New York , Columbia University Mailman School of Public Health
Current Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2020)
Project Period Covered by this Report: September 1, 2015 through August 31,2016
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Children's Health , Endocrine Disruptors , Human Health
Objective:
Aim 1: We will assess the effects of prenatal PAH exposure on neuropsychological performance at 15-17 years of age in a cohort of 350 adolescents who have been followed since the prenatal period. Hypothesis 1: Prenatal PAH exposure adversely affects self-regulatory processes, as defined by a pattern of atypical neuropsychological function across the domains of cognition, behavior, and emotion. Specifically, higher PAH exposure will be associated with deficits in reasoning, attentional control, conflict resolution, inhibitory control, and emotional control, after accounting for postnatal PAH and other covariates.
Aim 2: We will assess the effects of prenatal PAH exposure on clinical outcomes at 15-17 years of age in the same adolescents. Hypothesis 2: Prenatal PAH exposure adversely affects clinical outcomes, as defined by a pattern of atypical function across the domains of cognition, behavior, and emotion. Specifically, PAH exposure will be associated with clinical symptoms as measured by (2a) the emergence of mood disturbances; (2b) the emergence of high risk behaviors; and (2c) the persistence of attention deficit/hyperactivity disorder (ADHD) symptoms (inattention, distractibility, and impulsivity), after accounting for postnatal PAH and other covariates.
Aim 3: We will examine the maturational trajectories of neuropsychological and clinical (cognitive, behavioral and emotional) development over time as a function of early PAH exposure. Hypothesis 3: Elevated prenatal PAH exposure is associated with distinctive developmental pathways from early childhood through adolescence, as compared to pathways for children with low prenatal PAH exposure. These developmental trajectories will differ by (3a) intercept/mean, (3b) slope, and (3c) points of inflection.
Aim 4: All three projects share a common cohort in which we will explore how prenatal PAH exposure dysregulates neurodevelopment (Project 1) and physical growth (Project 2) via its mediational effects on the brain (Project 3). Hypothesis 4: Differences in brain structure and perfusion (by MRI at age 9-12 years) will mediate the effects of prenatal PAH exposures on neurodevelopment (assessed in Project 1).
Progress Summary:
Aims 1 and 2
In the first 9 months of the project, we have focused on Aims 1 and 2 to prepare for neuropsychological and clinical testing, to integrate protocols, to establish scoring procedures, and to establish data transfer and management protocols. All three research projects in this grant are closely coordinated and share a common 4-hour assessment visit. We have been working during this period to integrate and pilot test the protocol, including the neuropsychological assessments (Project 1), the obesity assessments (Project 2), and the MRI assessments (Projects 2 and 3). Initial activities included the translation and back translation of all instruments into Spanish, and obtaining IRB approval for this work. This work now has been completed.
The order of test administration, including the flow/overlap of maternal and child assessments for all three projects, has been established. Final decisions about the timing of the self-administered and the tester-administered measures takes into consideration subject fatigue, the inter-digitation of interview and anthropometric measures, and a lunch break. Three pilot test subjects were required to determine the final ordering of the protocol, which includes transitions for the MRI components (Projects 2 and 3). Subjects experience neuropsychological testing and anthropometric testing in our CCCEH suite, and then are walked across the street to the MRI lab. The timing and sequence of testing has been adjusted to accommodate this flow. During this period, we have coordinated and pilot-tested the combined maternal and adolescent neuropsychological and obesity test protocols, including measures of hedonic eating, physical activity, food insecurity, weight cycling, weight loss surgery, and use of supplemental nutrition programs (Project 2). We have worked closely with the Data Core to establish methods for direct data entry, for data security, and for distributing data to study investigators. Methods development, training, and pilot testing will help ensure robust and unbiased results. We have been contacting the cohort members and informing them of the upcoming project recruitment phase and the responses have been universally positive.
Dr. Amy Margolis has worked closely with Ms. Wanda Garcia and Dr. Julie Herbstman to install the various computer-based paradigms for test administration and to coordinate data transfer directly to our DCC core for data management and entry.
In order to further probe responses indicating adolescent subject risk (harm to self or others), we have established a protocol for immediate scoring of high-risk instruments. During this study period, Drs. Rauh and Peterson worked closely to establish clinical cut points for each instrument, with decision rules for (1) immediate action or (2) mental health referral. These decision rules are now embedded in the instruments, so that the neuropsychological tester (Wanda Garcia) has clear guidance about how to proceed under the various conditions. High risk conditions include suicidal ideation and risk of harm to others that meet criteria for referral. The procedure involves immediate scoring of these test items, and, if any risk is determined, a phone call to the on-call clinician. Following this consultation, the subject may receive either (1) an accompanied walk to the psychiatric Emergency Department located across the street, or (2) non-emergency referral to a mental health resource.
In order to accommodate unanticipated delays and events (illnesses, extended length of assessment, family events) on the day of assessment, we have hired a clinical psychology doctoral student (Daniel Bell, Columbia University, Teacher’s College), with previous experience in clinical research studies, to attend all assessments and back up our test team. Daniel is being supervised by Drs. Virginia Rauh and Amy Margolis, as well as Dr. Jeanne Brooks-Gunn at Teachers College), and will be permitted to use some research data for his dissertation in collaboration with CCCEH researchers.
As described in detail in the progress reports for Projects 2 and 3, a major activity has been to establish the MRI imaging procedures for both the abdominal and the brain scan components of the grant. Maintaining the consistency of the scanner technology for the new age 16-18 brain scans with the technology we used for the age 9-11 brain scans (data collected under the auspices of two previous R01s) is a priority for the Center’s research. During this period, CCCEH investigators have been working to develop MRI pulse sequences with improved image quality and this work has involved researchers at the University of Southern California (USC), The Mailman School of Public Health, and the New York Obesity Research Center and consultations with a physicist at the New York Psychiatric Institute MRI Lab.
As a result of the challenges in developing abdominal scan methods for the 3T machines, the planned follow-up of the cohort and data collection has been delayed. We anticipate that we will begin collecting data from the study participants in June and we will accelerate our planned study subject recruitment and follow-up to make up for the delays we have experienced.
Aim 3
Data analysis of trajectories of child growth, adiposity and self-regulation through age 12 and physical activity at age 12 are underway and preliminary results were reported during the Children’s Centers webinar by Dr. Rundle (Rundle, “Exposures to Polycyclic Aromatic Hydrocarbons and Childhood Growth Trajectories and Body Composition: Linkages to Disrupted Self-Regulatory Processes”, 1/13/16).
Aim 4
With respect to the integration of data across all 3 projects, we have used this period to prepare the neuropsychological data (previously obtained at 9-12 years) for integration with neuroimaging data (as described in Project 3). Data sets were prepared and successfully transferred to Dr. Peterson, including syntax and coding for all derived variables, in April of 2016. Data analysis of the integrated Neuropsychological and MRI data has commenced (see Project 3 progress report).
Future Activities:
In the coming reporting period we will continue follow-up of the cohort members as they reach ages 16-18 years and expect to complete 135 follow-up visits. The next reporting period will focus on intensive data collection from the study subjects. Clinical visits during which the study participants will visit the Center’s clinical offices, complete the neuropsychological testing, and undergo anthropometric and fitness assessments and then have MRI scans at the CU Neurological Institute will be completed on weekdays and weekends. The recruitment and data collection will follow the approaches described in our grant application. We have been developing and testing rigorous data collection methods and the use of these approaches in the coming reporting period will ensure scientific rigor and robust results. The Data Core has established protocols for data acquisition, cleaning, storage and distribution to study investigators that will also ensure scientific rigor.
Our original proposal called for follow-up and data collection from 100 subjects in year one, two and three of the project and from 50 participants in year four. As a result of the challenges we experienced in developing a single MRI scan protocol that acquires both brain and abdominal images for Projects 2 and 3, the launch of participant recruitment and data collection was delayed. We anticipate beginning data collection in June of 2016 and thus expect to collect data from 30 participants in year 1 of the project. In year two and three we plan to complete recruitment at data collection for 135 participants to bring us back onto schedule by year four of the project.
Data analysis of trajectories of child growth, adiposity and self-regulation through age 12 and physical activity at age 12 are underway and preliminary results were reported during the Children’s Centers webinar. Drs. Rauh and Margolis will be working closely with Dr. Rundle on this analysis.
Dr. Rauh will continue to work with Dr. Peterson on all data analyses involving the integration of exposure, behavioral, neuropsychological and clinical data with MRI modalities. Statistical models will be specified and implemented in each modality, incorporating relevant covariates and addressing potential confounds as indicated. Findings will be interpreted and, based on those interpretations, manuscripts will be prepared and submitted for publication.
Relevant Websites:
Columbia Center for Children’s Environmental Health Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R836154 The Columbia Center for Children’s Environmental Health Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836154C001 The Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
R836154C002 The Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue
R836154C003 An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.