Evidence from epidemiologic and animal model studies of autism (ASD) supports a role for pre- and postnatal immune and infectious factors in autism pathogenesis. However, associations with specific pathogens, patterns of immune response, fever and exposure to antibiotics, antipyretics, analgesics and micronutrients have not been rigorously addressed. This project will leverage the unique resources of the Norwegian Autism Birth Cohort (ABC) and the Center for Infection and Immunity (CII) for insights into the role of infection, immunity and inflammation in autism through pursuit of three complementary aims that address not only immune activation, fever and drug and micronutrient exposures during gestation per se, but also the timing of these phenomena.
In Aim 1 we will investigate the relationship of infectious, immune and inflammatory events to ASD risk using prospective questionnaire data about the following exposures in ASD and control mother- child pairs: a) infection;b) presence, timing and duration of fever, c) autoimmune and allergic conditions, d) antipyretics (acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]), analgesics and antibiotics, and e) micronutrients that modify immune function (vitamin D, zinc) or mitigate antibiotic anti-folate effects (folate).
In Aim 2 we will define the immune signatures associated with ASD using multiplexed immunoassays (Luminex) to compare levels of 61 immune/inflammatory molecules in plasma samples from ASD and control mothers (mid-gestation, birth) and children (umbilical cord blood).
In Aim 3 we will examine the role of specifi infectious agents in ASD by measuring maternal and child antibodies to influenza virus;ToRCH pathogens T. gondii, rubellavirus, cytomegalovirus and herpes simplex viruses 1 and 2;and Group B streptococcus and E. coli using luciferase immunoprecipitation systems (LIPS) and multiplexed immunoassays (Luminex). In concert these aims have the potential to identify factors and biomarkers for ASD risk that could facilitate early diagnosis and intervention. The Research Council of Norway has reviewed the proposal and guaranteed funding to a maximum of NOK 5 million ($834,000), to support the Norwegian segment of the project, contingent on NIH support.

Public Health Relevance

Epidemiologic and animal model studies suggest that immune activation in early life may contribute to autism pathogenesis;however, potential triggers and modifiers of immunity have not been rigorously examined. This project will leverage the unique resources of the Norwegian Autism Birth Cohort (ABC) and the Center for Infection and Immunity to pursue three complementary aims that address this challenge: Aim 1, analyze prospective data on pre- and postnatal infections, fever, comorbid immune disorders and drug and dietary exposures;Aim 2, examine serial maternal and infant (cord blood) plasma using sensitive, multiplexed serological assays to establish objective evidence of innate immune and inflammatory responses;and Aim 3, test for exposure to specific pathogens using a novel high throughput serological platform.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
High Priority, Short Term Project Award (R56)
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Developmental Brain Disorders Study Section (DBD)
Program Officer
Moy, Claudia S
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Columbia University (N.Y.)
Public Health & Prev Medicine
Schools of Public Health
New York
United States
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Hornig, M; Bresnahan, M A; Che, X et al. (2018) Prenatal fever and autism risk. Mol Psychiatry 23:759-766
Mahic, Milada; Mjaaland, Siri; Bøvelstad, Hege Marie et al. (2017) Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring. mSphere 2:
Mahic, Milada; Che, Xiaoyu; Susser, Ezra et al. (2017) Epidemiological and Serological Investigation into the Role of Gestational Maternal Influenza Virus Infection and Autism Spectrum Disorders. mSphere 2: