Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incur substantial suffering for patients and major challenges to our health care system. It is now estimated that ASD affects about 1 in 68 children, with a male:female ratio of 4:1. Both genetic and environmental factors contribute to ASD, but environmental factors have been understudied. Because environmental factors are potentially modifiable they should be a research priority. This effort has been hampered by the challenges of acquiring accurate and relevant exposure measures in large, unbiased, epidemiologic cohorts. Among the many environmental exposures to which humans are exposed, endocrine disrupting chemicals (EDs) have perhaps the best-known effects on neurodevelopment in pediatric populations. Several of these chemicals, particularly when exposure is prenatal, have been linked to autism-related phenotypes, and sex- differences in these associations have been documented. EDs have been shown to affect GABA and glutamate neurotransmission, which have prominent roles in ASD. Therefore, EDs are promising candidates as environmental triggers for ASD. To our knowledge, no prior study has been able to robustly link prenatal ED exposure to ASD. The goal of this application is to determine whether prenatal exposure to five classes of EDs impacts ASD risk. To achieve this, we will use stored samples from a serum biobank in southern Sweden and link these to population-based registries that include individual-level perinatal, diagnostic, medical, and demographic information (117,318 births in the years 1998-2007). We will randomly select and validate 600 ASD cases (oversampling females to include 200 females, 400 males) and 600 controls with similar sex and birth year distributions. By measuring concentrations of 38 EDs in five chemical classes in maternal serum samples we will address the following three integrated specific aims: First, determine the associations between ASD risk and prenatal serum concentration of our target EDs and their mixtures; Second, determine whether gender modifies sensitivity to prenatal ED exposure resulting in sex-dimorphic ED-ASD associations; Third, determine whether concentrations of EDs, singly and in combination, contribute to differences in ASD phenotype and their severity.

Public Health Relevance

Using existing population-based resources, our goal is to examine how exposure to endocrine disrupting chemicals in pregnancy contributes to risk of developing autism spectrum disorders. This approach will set a new bar and accelerate our understanding of the contribution of the environment to autism and related conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES026904-02
Application #
9349499
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lawler, Cindy P
Project Start
2016-09-30
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029