Imagine autism not as a single puzzle, but as a gallery of mosaics, each piece shaped by different traits, genes, and life experiences. Scientists have long known the condition is complex, but cracking the code has been a challenge.
Enter a team from Princeton University and the Simons Foundation, who dove into data from over 5,000 children and used computer models to group kids by shared traits, like how they interact, develop, and behave.
The big discovery? Four distinct types of autism, each with its own biological signature and clinical presentations.
Why does this matter? Because it opens the door to personalized care, support, and treatments that match each person's unique profile, rather than a one-size-fits-all approach.
Instead of looking at just one characteristic at a time – say, social skills or repetitive behaviors – researchers zoomed out to read the whole book of each child's experience. Using a "person-centered" lens, they explored over 230 traits per child, from how they correlate with factors like developmental milestones to medical history.
This wide-angle view revealed four distinct subtypes of autism: Social and Behavioral Challenges, Mixed ASD with Developmental Delay, Moderate Challenges, and Broadly Affected. Each subtype is characterized by a unique combination of developmental, medical, behavioral, and psychiatric traits.
Individuals in the Social and Behavioral Challenges group exhibit classic signs, including having difficulty with social interaction and repetitive behaviors. But they also hit major developmental milestones like walking and talking right on schedule.
Imagine a child who speaks fluently but struggles to connect in conversations or prefers routines so much that change feels overwhelming. Yet behind the scenes, there's emotional turbulence. ADHD, anxiety, depression, or OCD are often associated with this group. This is the largest subtype detected, making up 37% of the study.
The Mixed ASD with Developmental Delay group takes a slower path, walking and talking later. But unlike the first type, they're less likely to wrestle with anxiety or disruptive behaviors. The "mixed" part in the name? Their autism traits vary widely. One child might struggle with eye contact, while another finds comfort in repetition.
It's a patchwork of highly heterogeneous experiences. This group makes up 19% of the study.
Individuals with Moderate Challenges walk a quieter path through the spectrum. Their autism traits, like social quirks or repetitive behaviors, are present but dialed down. Think of a child who prefers routines or has unique ways of expressing themselves, but blends in more easily with their peers. They typically reach developmental milestones on time and rarely face additional psychiatric conditions. They make up 34% of the study.
The Broadly Affected group is the most emotionally charged subtype. These individuals face delays in walking and talking, struggle deeply with communication and social interaction, and experience intense repetitive behaviors. But that's not all, they often face emotional challenges like anxiety, depression, and mood swings, making daily life more complex. They represent just 10% of the study, but they face the greatest challenges.
With autism's strong genetic roots and a wide range of implicated genes, this new classification offers a more precise map of the spectrum and a promising path toward more personalized support.
"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 study co-author Jennifer Foss-Feig.
Most studies hunt for single genes, but this research zoomed out to find distinct genetic groupings. Instead of asking, “Which gene causes autism?” researchers asked, “What kind of autism does this child have, and what’s the genetic story behind it?”
Take the Broadly Affected and Mixed ASD with Developmental Delay groups. On the surface, they share traits, like developmental delays and intellectual challenges. But peek behind the curtain, and you'll find different genetic scripts driving their experiences.
The Broadly Affected group carries the highest number of damaging de novo mutations, genetic changes that pop up spontaneously. These mutations suggest a more complex and intense biological origin. In contrast, children in the Mixed ASD with Developmental Delay group are more likely to carry rare inherited variants, genetic quirks passed down quietly through generations.
One of the studies more interesting findings came when the researchers looked at when different genetic changes took effect in children. Most autism-related genetic changes were thought to happen before birth, but that wasn't always the case.
The Social and Behavioral Challenges group showed mutations in genes that activate later in childhood. These kids often hit early milestones like walking and talking on time, but face social and emotional hurdles as they grow. Their autism is usually diagnosed later.
"By integrating genetic and clinical data at scale, we can now begin to map the trajectory of autism from biological mechanisms to clinical presentation," explained co-author Chandra Theesfeld.
Now, with distinct subtypes identified, researchers can explore the unique engines driving each one, whether it's spontaneous mutations, inherited quirks, or genes that activate at different life stages. This shift could reshape both autism research and clinical care, helping clinicians anticipate different trajectories in diagnosis, development, and treatment.
While the current work defines four subtypes, "this doesn't mean there are only four classes," said Aviya Litman, co-lead author on the study. "It means we now have a data-driven framework that shows there are at least four, and that they are meaningful in both the clinic and the genome."
Beyond its contributions to understanding autism subtypes and their underlying biology, the study offers a robust framework for characterizing other complex, heterogeneous conditions and finding clinically relevant disease subtypes. This opens the door to countless new scientific and clinical discoveries.
The findings are presented in Nature Genetics.
Source: Princeton Engineering
