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Metabolomic study finds biomarkers predictive of autism in newborns
Last reviewed: 02.07.2025
A recent study published in the journal Communications Biology uses metabolomics in newborns to identify markers that may predict the development of autism spectrum disorder (ASD).
Biomarkers for ASD
Children with ASD have difficulties with social interactions, language, and restricted or repetitive interests or behavior patterns. Even with treatment, only 20% of them live independently as adults after being diagnosed with ASD in childhood.
Previous studies have identified metabolic and biochemical markers for ASD in children and adults that vary by age, gender, and symptom severity. Many of these markers are related to brain structure and function, the immune system, the autonomic nervous system, and the microbiome. However, no single genetic or environmental factor explains all cases of ASD in children.
Cellular danger response (CDR) model
The cellular danger response (CDR) model describes metabolic pathways linking environmental and genetic stressors to altered development and ASD. CDR extends from the point of stressor exposure outward, following various changes in metabolic, inflammatory, autonomic, endocrine, and neurological responses to these injuries or stresses.
ASD is more likely to follow CDR when stressors occur in fetal life or early childhood. These stressors affect four areas that are part of CDR: mitochondria, oxidative stress, innate immunity, and microbiomes. Extracellular adenosine triphosphate (eATP) is a fundamental regulator in all CDR pathways.
ATP as a signaling molecule
ATP is the energy currency for all living things on Earth. Approximately 90% of ATP is generated within the mitochondria and is used in all metabolic pathways. Outside the cell, eATP functions as a messenger molecule, binding to purine-responsive receptors on the cell to warn of danger and elicit a generalized CDR response.
ATP in metabolism in ASD
Dysregulated purine metabolism and purinergic signaling in response to ATP have been identified in experimental and human studies and confirmed by multiomics analyses. The role of eATP is key to multiple aspects of neurodevelopment altered in ASD, including mast cells and microglia, neural sensitization, and neuroplasticity.
Research results
Infants in the pre-ASD and typically developing (TD) groups did not differ in their exposure to environmental factors during pregnancy and infancy. About 50% of infants in the pre-ASD group showed developmental regression compared with 2% in the TD group. The mean age at ASD diagnosis was 3.3 years.
Metabolites were elevated above average in the ASD birth cohort and continued to increase by more than half at age five compared to the birth cohort. These metabolites included stress molecules and the purine 7-methylguanine, which coats newly formed mRNA.
The study findings confirm that ASD is associated with metabolic profiles that differ from those of typically developing children, varying with age, gender, and disease severity. These changes are reflected in the abnormal neurobiology of ASD.
Taken together, the data may indicate that failure to reverse the purine network causes failure to reverse the GABAergic network. Loss of inhibitory connections reduces natural damping, thereby allowing excessive excitability of calcium signaling in the RAS network.
Future research could use these findings to develop better screening tools for newborns and infants to identify those at risk for ASD. This could aid in early identification and intervention for affected children, ultimately improving treatment outcomes and reducing the prevalence of ASD.