Scientists identify four different autism subtypes

Researchers analyzing data from more than 5,000 children with autism have identified four clinically and biologically different subtypes of the condition, each with unique genetic characteristics and developmental trajectory.

The discovery can enable more personalized diagnosis and treatment of autism spectrum disorder.

The study, published on natural genetics, uses computational models for grouping individuals based on combinations of more than 230 features rather than finding genetic links to individual features. This human-centered approach reveals subtypes corresponding to different patterns of genetic variation and clinical outcomes.

Four different autism demonstrations

The research team led by Princeton University’s Olga Troyanskaya used data from Spark, a major autism research program, to identify four autism subtypes. Each subtype shows different developments, behaviors, and psychiatry:

• Social and Behavioral Challenges (37%): Core autistic characteristics with typical developmental milestones, but often occurring concurrent conditions (such as ADHD, anxiety and depression)
• Mixed with developmental delayed ASD (19%): Future development milestones, but usually without mental illness
• Medium Challenge (34%): mild autistic behavior with typical developmental and non-psychotic conditions
• Wide impact (10%): The most serious manifestations, development delay, communication difficulties and multiple psychiatric conditions

Genetic characteristics match clinical manifestations

Each subtype showed unique genetic characteristics aligned with its clinical characteristics. The highest proportion of damage was caused by de novo mutations (not inherited from parents) in the widely affected population, while mixed ASDs with developmental delayed groups were more likely to carry rare genetic variants.

These genetic differences indicate different biological mechanisms of surface similar symptoms. “What we see is not only a biological story of autism, but also a variety of very different narratives,” explains Natalie Sauerwald, an associate research scientist and co-leading writer at the Flatiron Institute.

Studies have shown that the time of genetic disruption of autism subtypes varies during brain development. Although it is believed that genetic effects have many genetic effects, the social and behavioral challenge subtypes (which were later diagnosed) indicate active genetic mutations in childhood, suggesting postnatal biological mechanisms.

The impact of precision medicine

“Understanding the genetics of autism is crucial to revealing the biological mechanisms that contribute to this condition, enabling early, more accurate diagnosis and guiding personalized care,” notes Troyanskaya, who guides Princeton’s precision health.

These findings address the long-term challenges of autism research. Previous genetic studies are often lacking because they view autism as a disease. “It’s like trying to solve a puzzle puzzle without realizing that we’re actually looking at multiple different puzzles,” Sauerwald observed.

Jennifer Foss-Feig, co-author of the Simons Foundation, explains the clinical potential: “Learning more genetic causes for autism may lead to more targeted developmental monitoring, precise treatment, and tailored support and adaptability at school or work.”

Biological pathways and therapeutic goals

This study identified different biological processes that influence each subtype. The social and behavioral challenge group showed disruptions in chromatin tissue and DNA repair, while ASD mixed with the developmental delay group mixed with the problems of neuronal signaling and membrane function.

Analysis of developmental gene expression patterns showed that each subtype affects different brain cell types at different developmental stages. This timing is consistent with clinical manifestations – the group with delayed development in the early stage showed genetic disruption of active genes during fetal development, while the group with subsequently presented active gene mutations after birth.

The study validated these findings in an independent cohort, demonstrating the robustness of four auxiliary classification systems.

Autism Change Research

This work represents a shift from seeking a universal explanation of autism to studying the paradigm shift in the different genetic and biological processes of each subtype. “The ability to define biologically meaningful autism subtypes is fundamental to the precise medical vision of neurodevelopmental status,” Sauerwald stressed.

For families, understanding the child’s autism subtype can make it clear about symptoms, treatment and long-term planning. This study also provides a framework for studying other complex conditions, where multiple biological mechanisms may contribute to similar clinical manifestations.

Although the study defines four subtypes, the researchers noted that this represents the starting point. “That doesn’t mean there are only four classes,” clarified co-leader writer Aviya Litman. “This means we now have a data-driven framework that shows that there are at least four and that they make sense in the clinic and in the genome.”

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