The proposed study will replicate and extend an innovative investigation of biologic markers for autism using archived prenatal and newborn specimens from mother-baby pairs. Funded by the NIMH (R01 MH72565) for an initial three-year period, this project, known as the Early Markers for Autism (EMA) Study, is the first large, population-based case-control study to utilize these very early biologic specimens to elucidate underlying causes of autism. The study includes three groups: children with autism spectrum disorders (ASD), children with mental retardation (MR) but not autism, and children selected at random from the general population (GP). The scientific and conceptual focus of the EMA Study is on immunologic and genetic susceptibility factors, environmental exposures, and the interplay of genes with environment, operating either directly on neurodevelopment, or indirectly via dysregulation of the immune system. Preliminary results from the first funding cycle indicate that the mid-pregnancy immune profile of mothers of children with ASD is dysregulated in comparison to mothers of control children. Levels of select cytokines (IFN-gamma, IL-4, IL-5, IL-6) are elevated, and maternal antibodies to fetal brain proteins are present more often in case than control mothers. In addition, polymorphisms in select immune function genes are more common in mothers (IFN-gamma) and children (IL-6) with autism. This renewal application seeks funding for an additional 5-year period to further these initial findings by conducting a much larger case-control study among a new sample of 1,200 mother-baby pairs (400 ASD, 400 MR, 400 GP controls), with an added family-based component that includes 60 siblings of ASD cases and 60 siblings of MR controls. Specimens will be analyzed for markers of immune system function (cytokines, chemokines, antibodies to fetal brain), environmental exposures (organochlorine pesticides, PCBs, and PBDEs), and candidate single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) regulating immune function, xenobiotic metabolism and detoxification, and maternal-fetal transport. This large sample size will ensure sufficient statistical power for the examination of relatively rare exposures, phenotypic subgroups of ASD, and ethnic subgroups. Findings from this study will likely define areas for further investigations of physiologic mechanism and will provide normative data on unaffected controls. In the long-term, a better understanding of the underlying biology may suggest appropriate strategies for early intervention and contribute to the eventual prevention of this often devastating and usually life-long disability.
The proposed study will continue an investigation of prenatal and newborn biologic markers for autism previously funded by NIH. The goal of the new study is to investigate further the role of prenatal and newborn immunologic factors, genetic susceptibility factors, and environmental exposures by evaluating stored prenatal (maternal) and newborn blood specimens for children with autism, children with other developmental disabilities, and population controls. We anticipate that the results of this study will contribute to identifying factors that increase the risk for autism and may lead to eventual prevention of autism and related disorders.
|Traglia, Michela; Croen, Lisa A; Jones, Karen L et al. (2018) Cross-genetic determination of maternal and neonatal immune mediators during pregnancy. Genome Med 10:67|
|Lyall, Kristen; Yau, Vincent M; Hansen, Robin et al. (2018) Prenatal Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect 126:017001|
|Jones, K L; Croen, L A; Yoshida, C K et al. (2017) Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol Psychiatry 22:273-279|
|Lyall, Kristen; Croen, Lisa A; Weiss, Lauren A et al. (2017) Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case-Control Study in California. Environ Health Perspect 125:087023|
|Lyall, Kristen; Croen, Lisa A; Sjödin, Andreas et al. (2017) Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect 125:474-480|
|Traglia, Michela; Croen, Lisa A; Lyall, Kristen et al. (2017) Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants. G3 (Bethesda) 7:1287-1299|
|Zerbo, O; Traglia, M; Yoshida, C et al. (2016) Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study. Transl Psychiatry 6:e783|
|Zerbo, Ousseny; Yoshida, Cathleen; Gunderson, Erica P et al. (2015) Interpregnancy Interval and Risk of Autism Spectrum Disorders. Pediatrics 136:651-7|
|Zerbo, Ousseny; Leong, Albin; Barcellos, Lisa et al. (2015) Immune mediated conditions in autism spectrum disorders. Brain Behav Immun 46:232-6|
|Yau, Vincent M; Lutsky, Marta; Yoshida, Cathleen K et al. (2015) Prenatal and neonatal thyroid stimulating hormone levels and autism spectrum disorders. J Autism Dev Disord 45:719-30|
Showing the most recent 10 out of 16 publications