Can we predict autism spectrum disorder years before symptoms appear?

Autism syndrome person and Autistic social developmental education disorder puzzle children symbol as a child special learning icon as jigsaw pieces coming together to form a young student head in a 3D illustration.
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New research study will analyse blood, collected from newborns, for over 1000 different molecules and chemicals which could reveal signs of autism spectrum disorder

Researchers at the University of California, San Diego School of Medicine have launched a Phase II research study to look for signs of another similarly devastating disorder, one that typically does not appear in seemingly healthy children until years later: autism spectrum disorder or ASD.

The presence of certain molecules and chemicals in the blood might predict autism risk years before symptoms appear, prompting early treatment and intervention.

How will the blood be analysed?

Within days of birth, a few drops of blood are collected from every newborn in California and across the United States, which are then stored on filter paper and screened for dozens of genetic and congenital disorders, such as phenylketonuria (PKU), an inherited metabolic disorder that can result in intellectual disability, seizures, heart and behavioural problems.

The UC San Diego Newborn Screening-Autism Risk Study is designed to determine whether the dried and stored blood drops of children later diagnosed with ASD contain within them the tell-tale presence and combinations of biological molecules and environmental chemicals that might predict the risk of a future ASD diagnosis.

Principal Investigator Robert Naviaux, MD, PhD, professor of medicine, paediatrics and pathology at UC San Diego School of Medicine explained the new study is important for two reasons: the dramatic rise in diagnosed cases of ASD and increasing evidence that early intervention in children at risk of ASD can significantly improve outcomes.

Naviaux said: “We know from the history of certain genetic diseases, such as PKU, that if children can be identified before the first symptoms have appeared, then the disease can be prevented, even though the children have the DNA mutations. I believe that over half of autism cases may be preventable if only we had a way to identify the children at risk before the first symptoms appear.”

ASD cases are on the rise

Cases of ASD have risen from 20 in 100,000 births in the 1970s to 1,700 in 100,000 in 2014, according to the U.S. Centers for Disease Control and Prevention – an 84% increase. Approximately one in 59 children is diagnosed with ASD. Statistics from the U.S. Department of Education and other government agencies indicate autism diagnoses are increasing at the rate of 10% to 17% per year.

Changes in diagnostic criteria and reporting practices account for 60% of the rise, at most, according to previously published research.

Naviaux said: “This means that even by the most conservative estimates, the prevalence of ASD has increased at least 34 times.”

The overarching question for Naviaux and others is why? Is it genetics? The environment?

Single gene mutations play a causal role in approximately 10% of ASD cases. The vast majority of ASD cases are idiopathic or of unknown cause, most likely the result of a combination of genes, environmental factors or something yet to be identified.

Naviaux explains: “Our genes have not changed significantly in the past 50 years. More than 1,000 genes can contribute to the risk and resistance a child has to ASD, but more than 95% of these genes are common variations also present in asymptomatic parents and children who don’t have ASD.

“A clue to how the genetics of ASD is misinterpreted is the fact that many of the genes that contribute to ASD are the same genes that contribute to other disorders like schizophrenia and bipolar depression. In most cases, DNA only sets what is possible, not what is destined.”

Focusing on the role of chemicals and compounds

The new Phase II study will focus on exposure and possible roles of chemicals and compounds (detected in blood) and how they might interact with genes. Researchers will use a blood test developed in Naviaux’s lab to analyse the presence of more than 600 metabolites –typically small molecules produced by metabolism, the life-sustaining chemical reactions in all organisms.

Metabolites from amino acids and antioxidants to vitamins and lipids serve diverse, crucial functions, including as fuel, signal carriers, structure providers, defenders and regulators among them.

Earlier research by Naviaux and others has found that persons with ASD appear to have a shared “metabolic signature.” That is, their biological chemistry is comparable, though their genetics are unique.

Measuring exposure to pollutants

Testing will also look at more than 400 environmental chemicals in each dried blood drop. Exposure to these chemicals, such as commonly used pesticides, flame retardants, air pollutants, lead, mercury and polychlorinated biphenyls or PCBs, has been linked to several neurodevelopmental disorders, including ASD.

Naviaux and colleagues believe that the majority of ASD symptoms are the result of a treatable metabolic syndrome triggered by persistence activation of the cell danger response (CDR), a natural and universal cellular reaction to injury or stress.

The researchers suggest that chronic CDR results in disrupted and incomplete healing at the metabolic and cellular levels. In ASD, the consequence may be dysfunctional neural circuits and internal systems, producing autism’s well-documented symptoms and behaviours.

Naviaux explains: “Metabolism is the real-time result of our genes interacting with the environment. Environmental chemical or biotoxin exposures –the ‘exposome’ — at critical developmental windows can produce delayed effects that become apparent only after months or years. By measuring metabolism and the exposome, it may be possible to identify children at risk for developing autism before the first behavioural symptoms appear.”

The study seeks 400 participants between the ages of three and 10 years old, meeting these requirements:

  • Born in California;
  • Have a confirmed diagnosis of ASD from a licensed clinician or be a healthy child not taking any prescription medications (200 participants from each group);
  • Born after a normal term pregnancy of 37 to 42 weeks;
  • Have not had a medical issue that required readmission to the hospital in the first month of life

The study requires parents of participating children to answer questionnaires covering pregnancy, labour and delivery, the child’s health history and that of the family.

Consented analyses will be conducted of dried blood drops recorded as part of California’s Newborn Screening program, which began in 1966 and now screens for 80 different genetic and congenital disorders. Blood spots have been saved and stored by the California Department of Public Health since 1982. No new blood tests or behavioural testing will be required for the Phase II study.

Naviaux said he hopes to screen and enrol the full complement of participants by June 2020. Analyses of the identified and retrieved blood spots is expected to be completed by June 2021.

He said: “We then hope to expand the testing program to states like New Jersey, New York, Pennsylvania and Washington by enlisting collaborators in each of those states who will be able to apply the new methods we have developed.

“Each new state has slightly different policies and regulations regarding the collection and storage of dried blood spots from universal newborn screening programs, so this medium-scale expansion study will teach us what will be needed to launch a national study.”

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