Four biologically distinct types of autism discovered in major new study

Autism spectrum disorder has long challenged both science and medicine. Each type presents differently – from speech delays to social difficulties to repetitive behaviors – making it hard to define and diagnose in a clear, unified way.

Parents, clinicians, and researchers have often worked with uncertainty, relying on broad categories that mask the condition’s complexity.

Researchers at Princeton University and the Simons Foundation have reshaped our understanding of autism. They identified four distinct clinical and biological subtypes using data from over 5,000 children in the SPARK autism cohort.

This shift toward a person-centered view may change how autism is diagnosed and treated in the future.

Autism types mapped with big data

Instead of linking individual traits to single genes, the team used a computational model that considered each child’s entire profile.

The researchers analyzed over 230 traits per child – spanning developmental milestones, social challenges, and repetitive behaviors.

This approach allowed them to group individuals into categories that reflect meaningful differences in both behavior and biology.

“Understanding the genetics of autism is essential for revealing the biological mechanisms that contribute to the condition, enabling earlier and more accurate diagnosis,” said Olga Troyanskaya, senior author of the study.

Four distinct autism types emerge

The study defined four categories of autism. The Social and Behavioral Challenges group includes children with classic autism traits but typical developmental progress.

The Mixed ASD with Developmental Delay group features children who reach milestones later but often lack anxiety or disruptive behaviors.

The Moderate Challenges group has milder autism traits, no delays, and few psychiatric conditions. The Broadly Affected group shows a wide range of severe symptoms including delays, repetitive behaviors, and mood disorders.

“These findings are powerful because the classes represent different clinical presentations and outcomes, and critically we were able to connect them to distinct underlying biology,” said Aviya Litman, Ph.D. student at Princeton and co-lead author.

Genetic clues behind autism types

Traditional genetic testing explains only a small portion of autism cases. This study went further by revealing distinct genetic profiles for each subtype.

The Broadly Affected group showed the highest rate of damaging mutations not inherited from parents.

In contrast, the Mixed ASD with Developmental Delay group had more rare inherited variants. Though the two groups share some traits, their genetic origins differ.

“While genetic testing is already part of the standard of care for people diagnosed with autism, thus far, this testing reveals variants that explain the autism of only about 20% of patients,” said Jennifer Foss-Feig of the Simons Foundation.

This study begins to bridge that gap by offering a clearer map of which variants relate to which traits.

“These findings point to specific hypotheses linking various pathways to different presentations of autism,” said Litman.

Developmental timing matters

The genetic influences behind each subtype do not act at the same time in development. In children with social and behavioral challenges, key gene mutations become active after birth. This matches the clinical picture of late diagnosis without early developmental delays.

In contrast, children in the Mixed ASD group carry mutations that affect the brain during fetal development. These genetic timelines correspond to the children’s milestones, diagnoses, and symptom severity.

“By integrating genetic and clinical data at scale, we can now begin to map the trajectory of autism,” said Chandra Theesfeld of Princeton.

New direction for autism research

This classification of autism types builds on years of collaborative research and was made possible through integration across genetics, psychology, and computation.

The work is part of Princeton Precision Health’s mission to connect biological insight with clinical care.

“It’s a whole new paradigm, to provide these groups as a starting point for investigating the genetics of autism,” said Theesfeld.

Instead of searching for one common cause of autism, researchers can now examine the distinct mechanisms behind each group.

Natalie Sauerwald, co-lead author, explained, “The ability to define biologically meaningful autism subtypes is foundational to realizing the vision of precision medicine for neurodevelopmental conditions.”

What this means for families

For families, this research may offer new clarity and direction. Knowing a child’s autism subtype could help with planning school support, medical care, and therapies.

“Understanding genetic causes for more individuals with autism could lead to more targeted developmental monitoring, precision treatment, and tailored support and accommodations at school or work,” said Foss-Feig.

Families may gain insight into what symptoms to expect and how to better plan for the future.

Autism model can work for other issues

While this study focused on autism, its methods may apply to other complex conditions.

By combining clinical traits with genetic data, researchers can now identify clear subtypes where once there was only disorder-level confusion.

“This opens the door to countless new scientific and clinical discoveries,” said Theesfeld.

The study is published in the journal Nature Genetics.

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