Major study on autism uncovers four distinct subtypes, ‘transforming’ diagnosis and treatment

Researchers have uncovered four distinct types of autism, each with its own genetic fingerprint, which could unlock the mystery of what causes the condition and how it can be treated.

A team at Princeton University and the Simons Foundation analyzed 5,000 children in SPARK, the most extensive autism research study in the country. They recorded their traits and separated the children into groups based on their behaviors.

They examined more than 230 behavioral and developmental traits—from social interactions to repetitive behaviors—and created four subtypes of autism: Social and Behavioral Challenges; Mixed Autism Spectrum Disorder (ASD) with Developmental Delay; Moderate Challenges; and Broadly Affected.

Then, they compared the subtypes with each child’s genetic profile, comparing patterns between the categories. Researchers looked for mutations that were inherited from parents, damaged mutations that were not inherited, and gene activity patterns. 

Scientists once believed autism’s genetic roots were prenatal, but the study found DNA glitches can determine subtypes before or after a child is born, and autism subtypes differ in the timing of genetic switches, which guide distinct stages of development.

Aviya Litman, a PhD student at Princeton University and co-lead author, said: ‘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.’ 

Researchers have determined that common gene variants account for only around 20 percent of ASD diagnoses, leaving the remaining 80 percent to a complex interplay of environmental factors, modifications to DNA that regulate gene expression, and gene-environment interactions that scientists still don’t fully understand.

Their findings unlock opportunities for parents to better understand their children and guide them through milestones with the proper treatment, such as occupational therapy. They could also usher in new targeted gene therapies for people severely disabled by autism. 

Researchers at Princeton and the Simons Foundation believe that identifying the subtypes of autism and how genetics play a role will help guide parents of neurodivergent children and pave the way for highly targeted treatments

To analyze data from the 5,000 children, researchers used a computational model to group children together based on a combination of over 230 different traits an individual could have, such as repetitive behaviors, sound sensitivity, gross motor delays, and aversion to certain textures.

This resulted in the creation of four subtypes, which the researchers linked to unique genetic profiles and developmental trajectories.

Natalie Sauerwald, associate research scientist at the Flatiron Institute and co-lead author, said: ‘What we’re seeing is not just one biological story of autism, but multiple distinct narratives.

‘This helps explain why past genetic studies often fell short — it was like trying to solve a jigsaw puzzle without realizing we were actually looking at multiple different puzzles mixed together.’

Children in the Social and Behavioral Challenges group (37 percent of the children in the study) display classic autism traits, including social difficulties and repetitive behaviors, yet still meet developmental milestones on time. 

Their high rate of co-occurring mental health conditions sets this subtype apart. ADHD, anxiety, depression, or OCD frequently appear alongside their ASD diagnosis.

The above chart shows the increases in autism diagnoses from 2011 to 2022 by age group, according to research published earlier this year in JAMA Network Open

These unseen challenges often dominate children’s needs. The fact that they’re still able to hit developmental milestones on schedule may explain why so many children with this subtype are not diagnosed until they begin to have more social demands in school age.

Those in the Mixed ASD with Developmental Delay group (19 percent) tend to lag behind their neurotypical peers in hitting key milestones, including first words and walking. Still, they do not show signs of anxiety, depression, or disruptive behavior that are more common in other subtypes.

The ‘mixed’ label reflects their variability in core autism traits—some have severe social challenges but mild repetitive behaviors, while others show the opposite pattern.

Only the Mixed ASD with Developmental Delay group was more likely to carry rare inherited genetic variants. 

Children with the Moderate Challenges subtype (34 percent) represent those with the mildest form of the disorder and exhibit more subdued core traits of autism while hitting milestones generally on time.

Importantly, these children lack the psychological difficulties that children in the first subtype exhibit, which suggests that they may need less long-term care, such as medication and therapy.

The Broadly Affected group is the most severely impacted by the disorder and represents 10 percent of the children in the study.

They face a myriad of challenges, including developmental delays, social and communication difficulties, repetitive behaviors, and co-occurring psychiatric conditions like anxiety, depression, and mood dysregulation.

They’re also more likely to carry damaging gene mutations that they did not inherit from their parents. Other types had different genetic underpinnings. 

‘These findings point to specific hypotheses linking various pathways to different presentations of autism,’ Dr Litman said, referring to differences in biology between children with different autism subtypes.

An estimated 2.3 million children and 7million adults in the US have ASD.

Diagnoses are becoming more common by the year. According to the CDC, around one in 150 children were diagnosed with ASD in 2000. By 2020, that figure ballooned to one in 36.

A 2024 analysis of electronic health records for more than 12.2 million Americans found that diagnoses increased by approximately 175 percent over 11 years.

Public health experts, pediatricians, and child psychologists posit that the spike in diagnoses is due to broader acceptance of autistic and neurodivergent people and better screening in children.

Health and Human Services Secretary Robert F Kennedy Jr has made identifying the cause of autism and reasons for its increased prevalence a hallmark initiative.

He cites chemicals, diet and environmental toxins as possible causes of the increase.

Senior study author Olga Troyanskaya, director of the Princeton Precision Health and Lewis-Sigler Institute for Integrative Genomics, said: ‘Understanding the genetics of autism is essential for revealing the biological mechanisms that contribute to the condition, enabling earlier and more accurate diagnosis, and guiding personalized care.’