Metabolomics study finds biomarkers predictive of autism in newborns

A recent study published in the journal Communications Biology uses metabolomics in newborns to identify markers that may predict development autism spectrum disorders (ASD).

Biomarkers for ASD

Children with ASD experience difficulties with social interactions, language, and limited or repetitive interests or behavioral 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 depending on age, gender and severity of symptoms. 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 spreads outward from the point of exposure to the stressor, following various changes in the 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 the 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 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 trigger 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 supported by multi-omics 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 from the pre-ASD and typically developing (TD) groups did not differ in their exposure to environmental factors during pregnancy and infancy. About 50% of children in the pre-ASD group showed developmental regression compared with 2% in the TD group. The average age at diagnosis of ASD was 3.3 years.

Metabolites were elevated above average in the ASD newborn cohort and continued to increase by more than half at five years compared to the newborn 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 by age, gender, and disease severity. These changes are reflected in the abnormal neurobiology of ASD.

Taken together, the data may indicate that failure of normal purine network reversal causes failure of GABAergic network reversal. Loss of inhibitory connections reduces natural damping, thereby allowing calcium signaling to become overexcitable 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 may aid in early identification and intervention for affected children, which will ultimately improve treatment outcomes and reduce the prevalence of ASD.