Scientists Find a Hidden Biological Link Across Different Forms of Autism

Researchers led by Gaia Novarino at the Institute of Science and Technology Austria (ISTA) have identified shared biological changes across different genetic forms of autism, despite the disorder's extensive genetic diversity. The findings, published in the journal Nature, take a step toward explaining the molecular and cellular processes that drive autism spectrum disorder (ASD), a neurodevelopmental condition in which changes begin during early brain development and signs often appear in early childhood.

Hundreds of genes have been linked to autism, and scientists have not fully understood whether these many genetic causes converge on the same biological changes in the brain. Lena Schwarz, an ISTA alumna, worked with the Novarino group along with researchers from the Medical University of Vienna, the University of Vienna and CeMM to investigate that question as part of her PhD research.

The team used single-nucleus multi-omics sequencing, a technique that examines DNA, RNA activity and the epigenome — chemical modifications that switch genes on or off — within individual brain cell nuclei. Schwarz analyzed more than 250 samples representing high-risk ASD genes, drawn from two brain regions in both male and female mice at different stages of development.

Although each genetic model affected different genes, many disrupted the same brain cell types and molecular pathways, especially during early brain development, while each model also retained its own distinct molecular signature. Most of the shared differences showed up as temporary delays in cell maturation and the formation of neural connections rather than permanent damage, and many of these changes had disappeared by about two weeks after birth. The researchers also found that female mice responded differently to the autism-linked mutations than male mice.

The wide range of genetic causes behind ASD makes it unlikely that a single treatment will work for everyone, the researchers said. But the shared, time-sensitive developmental pathways identified in the study could point to future stage-specific approaches to treatment.