Researchers have disputed and discussed the biological underpinnings of autism for decades. It refers to a wide range of illnesses that are often diagnosed based on behavioral criteria rather than physical etiology. This symptom-based approach has prevented a more direct assessment of the autism spectrum, but this may be changing. Advances in numerous fields, including genome sequencing, neurophysiology, and the significance of the gut-brain axis, are coming together in novel ways, enhancing discoveries that were previously isolated to separate disciplines.
Researchers discovered that elevated levels of particular immune system chemicals at birth are connected with the likelihood of autism spectrum disease, laying the framework for a screening test.
Autism spectrum disorders (ASDs) are a diverse group of illnesses caused by a combination of genetic predisposition and environmental variables. Efforts to develop accurate biomarkers in genetics, neuroimaging, gene expression, and measures of the body’s metabolism are growing in an effort to better target the underlying causes of ASD for diagnosis and therapy.
A comprehensive study conducted by researchers at Columbia University Mailman School of Public Health and the Norwegian National Institute of Public Health discovered molecular markers of fetal inflammation that are linked to the chance of developing autistic spectrum disorder (ASD). These discoveries, which shed light on aberrant brain development, could potentially lead to the development of a test to screen for ASD at birth. The findings have been published in the journal Molecular Psychiatry.
We discovered immune signatures in mid-pregnancy blood samples from mothers and umbilical cord blood from children later diagnosed with autism that correlate with responses to infection and molecules important for the development of the brain and its blood supply.
Mady Hornig
The current study adds to the growing body of data that prenatal inflammation increases the likelihood of ASD. Previously, the researchers linked ASD risk to prenatal exposure to maternal fever, as well as influenza and herpesvirus type 2 infection – two of several putative triggers for maternal inflammation and ASD.
The presence of 60 molecular indicators of immunological response, such as cytokines and growth factors, was examined in the new study. Blood samples were collected from 957 children, about half of whom were eventually diagnosed with ASD, during pregnancy (maternal mid-gestational blood sample) and at birth (cord blood). The study connected ASD risk to clusters of inflammation-related chemicals, with distinct clusters observed in boys and girls. Interleukins such as IL1RA and IL4 were among the most prognostic molecules. TNFα, Serpin E1, VCAM1, and IL1β are four chemicals hypothesized to be important in prenatal brain development that have been associated to ASD risk in both sexes. Biomarkers taken at delivery were only marginally less predictive than those taken during pregnancy.
“Our findings point to a vulnerable phase during pregnancy when inflammation can interfere with central nervous system development,” explains first author Xiaoyu (Jason) Che, Ph.D., assistant professor of biostatistics at Columbia Mailman School of Public Health.
“We discovered immune signatures in mid-pregnancy blood samples from mothers and umbilical cord blood from children later diagnosed with autism that correlate with responses to infection and molecules important for the development of the brain and its blood supply,” says study co-first author Mady Hornig, MD, associate professor of epidemiology at Columbia Mailman School.
“This work demonstrates the particular power of prospective cohorts for revealing illness roots,” says corresponding author Ezra Susser, professor of epidemiology and psychiatry.
“This publication is the result of more than 20 years of data and sample collection and analysis with our colleagues at the Norwegian Institute of Public Health. Our future study will focus on identifying inflammation triggers and the linkages between those triggers and genetic susceptibility “W. Ian Lipkin, John Snow Professor of Epidemiology and neurology and pathology professor, made the statement.
About the Autism Birth Cohort (ABC) Study
The Autism Birth Cohort (ABC) study was carried out within a large Norwegian cohort of over 100,000 children who had been observed since before birth. ABC is a collaboration between researchers at the Norwegian National Institute of Public Health (NIPH) and the Columbia Mailman School, and it is directed by a Steering Committee of four people: Camilla Stoltenberg and Per Magnus in Norway, and Ian Lipkin and Ezra Susser at Columbia. “The ABC project is unusual in terms of the scale, depth, and breadth of both biological and social data on ASD,” Susser said.
The National Institutes of Health (grants NS047537 and NS086122), the Jane Botsford Johnson Foundation, the Korein Foundation, the Simons Foundation Autism Research Initiative, the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, and the Research Council of Norway funded the study (grants 189457, 190694, 196452).
The funders had no say in the study’s design, data collecting, and analysis, or the decision to publish the work. None of the authors disclosed any financial or other biomedical interests or potential conflicts of interest.
