What Do We Know About the Causes of Autism?

Medscape

05-05-2025

The latest surveillance data from the US Centers for Disease Control and Prevention (CDC) show a steep rise in the prevalence of autism spectrum disorder (ASD), extending a years-long trend of increasing diagnoses.
While greater awareness and improved diagnostic criteria have likely played a role, other potential contributing factors remain unclear and questions persist about what's truly driving this phenomenon.
These new surveillance data came on the heels of an April 10 announcement by US Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr, who set a September deadline to determine the cause of what he called an 'autism epidemic.'
'By September, we will know what has caused the autism epidemic and we'll be able to eliminate those exposures,' Kennedy said.
However, many scientists who have spent their careers studying ASD are deeply skeptical that a definitive answer could be found in just a few months — if at all.
What Do the Latest Data Show?
The CDC regularly compiles data on ASD prevalence through the Autism and Developmental Disabilities Monitoring (ADDM) Network. The findings are considered to be among the most reliable snapshots of autism rates in children. The CDC's most recent data from the 2022 ADDM surveillance cycle are based on 393,353 8-year-olds across 16 US sites.
The CDC report shows that ASD affects 1 in 31 children (32.2 per 1000), up from 1 in 36 in 2020 and 1 in 150 in 2000. ASD continues to be more common in boys than girls (ratio 3.4:1).
ASD prevalence was higher among Asian/Pacific Islander, Black, and Hispanic children than White children, continuing a pattern first observed in 2020.
Children born in 2018 were more likely to be diagnosed by age 48 months compared with those born in 2014, suggesting increased early identification consistent with historical patterns.
Why Is ASD Prevalence Rising?
The CDC's latest findings have prompted renewed scrutiny over why ASD prevalence continues to rise.
CDC investigators noted several factors that may be driving the increase, including broader diagnostic criteria, greater awareness among parents and pediatricians, and improved access to specialized services.
Together, these shifts mean children who may have been overlooked in previous decades are now being identified.
Kennedy has long expressed concern about environmental toxins and their potential role in ASD. At an April 16 press conference, he claimed that such toxins disrupt neurodevelopment and are behind the rising caseload. He described autism as 'a preventable disease' and pledged to identify the environmental culprit by September.
'We're going to follow the science no matter what it says,' Kennedy said. 'And we will have some of the answers by September.'
In a statement, the International Society for Autism Research said referring to the condition as a 'preventable disease' is 'out of touch with contemporary, evidence-based understanding of autism.'
'Based on current autism research, we know that there are many causes of autism, and virtually all of these occur prenatally,' the statement continued. 'In other words, you are born with autism.'
What's Driving ASD: Genes, Environment, or Both?
A robust body of evidence points to a substantial genetic component in ASD etiology. Studies of twins dating back to the 1970s have consistently shown that the vast majority of ASD is due to genetics, said Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai in New York City.
'With advances in genetic technology and analytic methods, hundreds of specific genetic changes have now been identified and are commonly accepted to cause autism. Yet the same twin studies show that if one identical twin has ASD, the other may not about 10% of the time, leaving room for some environmental influence,' Kolevzon told Medscape Medical News .
'Environmental effects may be acting through epigenetic mechanisms where certain factors, as of yet unidentified, influence the expression of genes. However, despite being an active area of study, no widespread environmental effects have been reliably established to date,' he added.
When it comes to environmental contributors, a substantial amount of research has focused on exposures during the prenatal period — a critical window for neurodevelopment.
For example, a 2019 JAMA Pediatrics population-based cohort study of 132,256 births showed that maternal exposure to nitric oxide during pregnancy was associated with increased risk for ASD in offspring.
Investigators leading a 2022 study of 294,937 mother-child pairs found that exposure to particulate matter 2.5 in the first two gestational trimesters were associated with increased ASD risk in children. In addition, a 2022 study from France showed prenatal exposure to organophosphate pesticides was linked to an increase in autistic traits among 11-year-old children.
Maternal metabolic conditions may also play a role. In April 2025, a meta-analysis of 202 studies including more than 56 million mother-child pairs showed that children born to mothers with gestational diabetes were 25% more likely to be diagnosed with autism. Researchers have also linked ASD risk to preterm birth and advanced parental age.
It's thought that these exposures likely act as modifiers — influencing gene expression, immune activation, or neuronal development — rather than standalone causes.
Gut-Brain Link?
An emerging area of autism research involves the gut microbiome and whether gut dysbiosis contributes to ASD risk.
'There have been several studies showing that there is gut dysbiosis in autism, and that it correlates with autism symptoms,' Lisa Aziz-Zadeh, PhD, professor, Department of Psychology, University of Southern California, Los Angeles, told Medscape Medical News .
'However, we know that any behavioral differences must be via gut microbiome/metabolite interactions with the human nervous system,' she said.
In an April 2025 study published in Nature Communications , Aziz-Zadeh's team was the first to identify links between gut microbial tryptophan metabolites, ASD symptoms, and brain activity in individuals with autism, particularly in brain regions associated with interoceptive processing. This points to a 'mechanistic model by which gut metabolites may impact autism,' she said.
'It's possible that addressing gut imbalances (via diet, probiotics, prebiotics, fecal transplants) may be helpful. However, we still don't know if there is a critical age where this may need to happen (prenatal, early life). There is still a lot of work to be done to answer this question,' she said.
In another recent study, microbiota transfer therapy led to significant improvements in gastrointestinal (GI) symptoms, autism-related symptoms, and gut microbiota in children with ASD.
The effects of the initial treatment on both gut microbiota and GI symptoms were maintained at the 2-year follow-up, with continued improvement in autism-like behaviors, the researchers reported.
A Realistic Deadline?
When Kennedy declared a September deadline for identifying the cause of autism, reaction was swift. Advocacy organizations, professional societies, and many research scientists expressed skepticism regarding the feasibility of such a deadline, noting that complexity argues against finding a single cause.
'The odds of identifying a single factor that causes autism, whether genetic or environmental, is zero,' said Kolevzon.
The 5-month timeline Kennedy set 'gives people a false sense of hope' and risks politicizing science, the Autism Society of America said in a statement. 'The Autism Society of America finds the administration's claim that 'we will know what has caused the Autism epidemic and we'll be able to eliminate those exposures' — to be harmful, misleading, and unrealistic.'
Aziz-Zadeh said that 60%-90% of the causes of autism are likely due to genetic factors. 'However, since that number isn't 100%, there are also contributing environmental factors — what those might be, we still don't know — and likely there isn't a single one,' he said.
In a letter signed by more than 130 scientists, the newly formed Coalition of Autism Scientists rejected Kennedy's 'false narrative' about the incidence and causes of ASD.
'We are unified in our commitment to conduct the highest quality research and build mutual respect and trust with the public. This trust is seriously threatened by the Secretary's interpretation of the rising prevalence rates and his plans to carry out a study that will deliver findings within a few months on an environmental toxin that causes autism,' the statement said.
An ASD Registry?
Equally concerning to many in the autism community was a recent announcement from the National Institutes of Health (NIH) about plans to establish a 'new disease registry' focused on ASD that would collect federal and private health data for upcoming autism studies. NIH Director Jay Bhattacharya, MD, PhD, made the announcement during a presentation to the Council of Councils on April 21.
However, HHS walked back that plan 3 days later, following an outcry from the autism community. HHS spokeswoman Vianca N. Rodriguez Feliciano told Medscape Medical News that the agency is not creating an autism registry but is developing a 'real-world data platform' linking existing datasets 'that maintains the highest standards of security and patient privacy while supporting research into autism and other areas such as chronic diseases.'
NIH is also investing $50 million to launch a comprehensive research effort aimed at understanding the causes of ASD and improving treatments by leveraging large-scale data resources and fostering cross-sector collaboration, Feliciano added.
Feliciano did not respond to follow-up questions from Medscape Medical News to clarify whether the data platform would include patient identifying information or such data sources as pharmacies, private insurers, and personal wearable sensors, as noted by Bhattacharya during his presentation.
Autism Speaks, an advocacy group, said that research should not focus solely on the causes of autism. 'We also need to invest in studies that lead to real improvements in people's lives — like better healthcare, education, job opportunities, and support at every stage of life for autistic people and their families,' the group said in a statement.