research on what causes autism

What Causes Autism? Study of 100,000 Kids Reveals New Clues

From genetics to fevers, Columbia psychiatrist and epidemiologist Mady Hornig discusses the possible roots of this mysterious condition.

Autism is, for the most part, an inherited disorder: scientists estimate that up to 80 percent of a child’s risk of developing it is determined by DNA. But environmental and behavioral risk factors may also play a role, and since rates of autism in the US are at an all-time high, new and expecting parents are eager to learn more about the roots of this complex condition. 

For the past two decades, a team of researchers including  Michaeline Bresnahan ’99PH,  Mady Hornig , W. Ian Lipkin , and Ezra Susser ’74CC, ’82VPS, ’93PH, all epidemiologists at Columbia’s Mailman School of Public Health, has been searching for nongenetic clues to explain why some kids develop autism and others do not. The researchers, in collaboration with the Norwegian Institute of Public Health and other Columbia scientists, have scrutinized the medical histories of more than one hundred thousand children, as well as those of their parents. Armed with unprecedented amounts of data, the researchers are investigating dozens of hypothesized risk factors for autism — everything from parental age to maternal infections to vitamin deficiencies. Columbia Magazine recently spoke to Hornig, who is herself the mother of an adult son with autism, about the team’s research.

What are the major risk factors for autism?

Well, a father’s age, which was one of the first risk factors identified a couple of decades ago, is certainly consequential. My colleague Ezra Susser published a major study on this subject in 2006. Using data collected in Israel, he showed that men who become fathers when they’re over the age of forty are six times more likely to have a child with autism than men who father kids before turning thirty. In 2016, I coauthored a larger study , which analyzed our Norwegian data together with information from Israel and three other countries, that confirmed the impact of paternal age while adding some new twists. We discovered that women at the beginning or end of their childbearing years — those in their teens or in their forties, roughly — are also more likely to have children with autism. And the biggest risk here is when older men have children with much younger women. There may be something about the big mismatch in age that can disrupt a child’s neurodevelopment. 

Is this a reason for certain couples to avoid having children?

No, not necessarily. The thing to keep in mind is that autism is an extraordinarily complex condition that’s probably influenced by hundreds of genetic, environmental, behavioral, and dietary factors, several of which may have to co-occur and reinforce one another for the condition to arise. So even though parental age is one of the most powerful variables, it probably accounts for 5 percent or less of any child’s total risk. 

Do any other factors rise to this level of importance?

One of our more recent discoveries is quite significant: we found that if a pregnant woman experiences a high fever in her second trimester, her child’s chances of developing autism increase by 40 percent. We’re not sure why this is, but molecular evidence suggests that inflammation in the mother’s body may be associated with a delay in the formation of blood vessels in the fetal brain during a critical point in the development of the central nervous system. 

Does it matter what causes the fever?

We suspect that any number of viral or bacterial infections can probably have this effect, but we’d need to conduct even larger studies to know for sure. Influenza appears to be implicated: the mothers of many of the children diagnosed with autism in our cohort suffered a serious bout of influenza in the second trimester. But the type of infection seems to be less important than its severity, since it’s the fever itself — indicative of a systemic, full-body inflammatory reaction — that we found to be strongly associated with autism. That said, I wouldn’t want to be alarmist. A lot of women experience fevers while they’re pregnant and go on to have perfectly healthy kids. Again, the risk this poses for any particular child is quite small. 

So what’s the takeaway for pregnant women or women who plan to get pregnant?

Get a flu shot. Get vaccinated against COVID-19. Wear a mask and practice social distancing. Keep your immune system strong by exercising and eating healthy food. And if you do get sick and have a high temperature, talk to your doctor about possibly taking an anti-inflammatory medication like ibuprofen. (Acetaminophen does not counter inflammation in the same way). Physicians have traditionally cautioned against taking ibuprofen while you’re pregnant because it carries a risk of miscarriage, especially in the first trimester, or possibly deformation of the baby’s heart if given close to the time of delivery, but administration of anti-inflammatory medications for fever during the second trimester might be discussed with one’s physician. At that stage, you really want to reduce a fever as quickly as possible. 

Are any dietary factors important?

We analyzed the diets of all of the women and children who participated in our project to see if any vitamin or mineral deficiencies contribute to autism. What jumped out of the data was that women who take supplements of folic acid, or vitamin B9, early in their pregnancy are almost 40 percent less likely to have a child with autism. That wasn’t a shock because folic acid, which is found naturally in leafy vegetables, beans, and eggs, has long been known to be essential for fetal brain development. But our research revealed that folic acid supplements only protect a fetus against autism if a mother begins taking them shortly before conception and throughout the first two months of pregnancy, which is earlier than many women start on prenatal vitamins. That’s why I suggest that women who are planning a pregnancy talk to their doctors about taking prenatal supplements before they conceive. 

We’ve also found preliminary evidence that heritable differences in how the body regulates levels of vitamin D in the body may be associated with autism in certain subsets of people with the condition, but we need to do additional research to confirm that.

Other researchers have claimed that altering an autistic child’s diet, such as by removing gluten, dairy, or other potential allergens, can sometimes ameliorate symptoms. Have you found any evidence that a child’s diet might contribute to the condition’s onset?

No, though it’s possible that dietary factors play such a role and that we’d just need larger studies with more statistical power to spot them. But we’ve tended to focus our investigations on pregnant women’s health in the Norway cohort because we believe that the roots of autism are likely established in the earliest stages of brain development, in the womb, and that improving our understanding of these processes holds promise for uncovering tractable pathways for prevention.

What are you looking at next?

Our findings about the role of fever in causing autism raise all sorts of questions. For example, we’d like to know if psychosocial stressors in the mother during pregnancy may pose a risk by triggering low-grade inflammation in the body that translates into neurodevelopmental risk for the child. The use of antidepressants by expectant mothers has previously been hypothesized as a risk factor for autism, but other data suggest that antidepressants themselves are unlikely to be the culprit; we’ve considered instead that underlying or untreated depression or anxiety may be the real danger. 

Do you expect that we’ll see a spike in autism cases as a result of the COVID-19 pandemic?

Yes, sadly, I think that’s possible. And not just because many pregnant women have been getting COVID-19, but also because many people, pregnant women included, have been dealing with serious mental stress during the pandemic. It will be a few years before we know if autism rates rise in response, because the condition is usually diagnosed around age three or later. It is also quite likely that rates may rise more generally for a range of neurodevelopmental conditions, including ADHD.

Autism’s prevalence in the US has nearly tripled since 2000. Why?

Part of the explanation is certainly that doctors are more aware of the condition and are diagnosing it more frequently. But my colleagues and I suspect that other factors, like people having children later in life or environmental changes that are making our bodies more vulnerable to infections and immunological problems, are contributing to the uptick in cases.

You’ve spoken publicly about your own experiences raising a son with autism. Is there anything that you wish you’d known back when you were pregnant?

You know, it’s interesting, because I just discovered, through my own participation as a subject in an unrelated medical study, that I have a genetic mutation that’s known to interfere in the body’s absorption of folic acid. So this tells me that it’s possible I wasn’t getting enough folic acid when I was pregnant back in the late 1980s, even though I was taking the recommended four hundred micrograms per day. Now, did a lack of folic acid cause my son’s autism? That’s way too simplistic, because there were probably lots of genetic and environmental factors involved. Did it contribute? Maybe. I certainly wish that I’d known I was susceptible to folate deficiency when I was pregnant, because then I could have talked to my obstetrician about it and explored solutions. 

What is the genetic variant you have? And are pregnant women routinely tested for it today?

The gene variant, which is carried by about 15 percent of all Americans, is located in the gene MTHFR . Pregnant women aren’t routinely tested for it, and a physician might initially balk at ordering it, unless he or she is knowledgeable of cutting-edge autism research and knows how to interpret its results. But if a woman can find a doctor who thinks the test is beneficial and she has good insurance, she might get it covered.

Are there any genomic tests that can tell an adult if he or she is likely to have a child with autism?

No, because the genetics of autism are still poorly understood. Although scientists have identified more than a hundred genes linked to the condition, we can’t say precisely what many of these genes do, nor the degree to which they increase an individual’s risk. There are some geneticists who will analyze and interpret men’s and women’s DNA in an attempt to estimate this risk. However, such analyses don’t offer definitive predictions, since we still haven’t identified all of the mutations involved in autism. Further, the influence of certain gene variants on autism may also depend on whether an individual is additionally exposed to specific environmental risks that may affect the function of that gene variant during key periods of early neural development — much as the rare inherited disorder phenylketonuria (PKU), caused by genetic mutations, can be treated by reducing or eliminating the amino acid phenylalanine from a child’s diet. A good source of information on this topic is the SPARK website of the Simons Foundation, a New York–based nonprofit that supports autism research.

Eventually, we’d like to get to the point where we’re able to recommend a whole range of preventive steps parents might take to mitigate the damaging effects of specific mutations they carry. But we still have a lot more work to do, both in terms of identifying the causes of autism and in understanding how various risk factors interact. Right now, we’re still building the scientific foundation for that kind of customized clinical care. 

For more information on this research, see the following articles from Columbia's Mailman School of Public Health:

Study Identifies Biomarkers Linked to Autism Risk

Could Flu During Pregnancy Raise Risk for Autism?

Autism Risk Linked to Fever During Pregnancy

Autism Risk Linked to Herpes Infection During Pregnancy

This article appears in the Spring/Summer 2022 print edition of Columbia Magazine with the title "In search of autism's roots." 

More From Health & Medicine

Sign up for our newsletter.

General Data Protection Regulation

Columbia University Privacy Notice

• Copy/Paste Link Link Copied

What causes autism?

Scientists don't know exactly what causes autism spectrum disorder (ASD).

Autism was first described in the 1940s, but very little was known about it until the last few decades. Even today, there is a great deal that we don't know about autism.

Because the disorder is so complex and no two people with autism are exactly alike, there are probably many causes for autism. It is also likely that there is not a single cause for autism, but rather that it results from a combination of causes.

Scientists are studying some of the following as possible causes of or contributors to ASD.

Genes and ASD

Genes:  Bits of DNA that carry instructions for "building" your body. Chromosomes: Packages of DNA and genes in the cells of the body.

A great deal of evidence supports the idea that genes are one of the main causes of or a major contributor to ASD. More than 100 genes on different chromosomes may be involved in causing ASD, to different degrees. 3 , 4

Many people with autism have slight changes, called mutations , in many of these genes. However, the link between genetic mutations and autism is complex:

• Most people with autism have different mutations and combinations of mutations. Not everyone with autism has changes in every gene that scientists have linked to ASD.
• Many people without autism or autism symptoms also have some of these genetic mutations that scientists have linked to autism.

This evidence means that different genetic mutations probably play different roles in ASD. For example, certain mutations or combinations of mutations might:

• Cause specific symptoms of ASD
• Control how mild or severe those symptoms are
• Increase susceptibility to autism. This means someone with one of these gene mutations is at greater risk for autism than someone without the mutation.

Interactions between Genes and the Environment

If someone is susceptible to ASD because of genetic mutations, then certain situations might cause autism in that person.

For instance, an infection or contact with chemicals in the environment could cause autism in someone who is susceptible because of genetic mutations. 1  However, someone who is genetically susceptible might not get an ASD even if he or she has the same experiences. 2

Other Biological Causes

Researchers are also looking into biological factors other than genes that might be involved in ASD. Some of these include:

• Problems with brain connections
• Problems with growth or overgrowth in certain areas of the brain
• Problems with metabolism (the body's energy production system)
• Problems in the body's immune system, which protects against infections
• Landrigan, P. J. (2010). What causes autism? Exploring the environmental contribution. Current Opinion in Pediatrics, 22 (2):219–225.
• Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., et al. (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry, 68 (11), 1095–1102.
• Eunice Kennedy Shriver National Institute of Child Health and Human Development. (2014). Common gene variants account for most genetic risk for autism. Retrieved March 2, 2018, from https://www.nichd.nih.gov/news/releases/072114-gene-variants-autism
• Pinto, D., Pagnamenta, A.T., Klei, L., Anney, R., Merico, D., Regan, R., et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 466, 368-372. Retrieved February 23, 2018, from https://www.nature.com/articles/nature09146

• Patient Care & Health Information
• Diseases & Conditions
• Autism spectrum disorder

Autism spectrum disorder is a condition related to brain development that impacts how a person perceives and socializes with others, causing problems in social interaction and communication. The disorder also includes limited and repetitive patterns of behavior. The term "spectrum" in autism spectrum disorder refers to the wide range of symptoms and severity.

Autism spectrum disorder includes conditions that were previously considered separate — autism, Asperger's syndrome, childhood disintegrative disorder and an unspecified form of pervasive developmental disorder. Some people still use the term "Asperger's syndrome," which is generally thought to be at the mild end of autism spectrum disorder.

Autism spectrum disorder begins in early childhood and eventually causes problems functioning in society — socially, in school and at work, for example. Often children show symptoms of autism within the first year. A small number of children appear to develop normally in the first year, and then go through a period of regression between 18 and 24 months of age when they develop autism symptoms.

While there is no cure for autism spectrum disorder, intensive, early treatment can make a big difference in the lives of many children.

Products & Services

• Children’s Book: My Life Beyond Autism

Some children show signs of autism spectrum disorder in early infancy, such as reduced eye contact, lack of response to their name or indifference to caregivers. Other children may develop normally for the first few months or years of life, but then suddenly become withdrawn or aggressive or lose language skills they've already acquired. Signs usually are seen by age 2 years.

Each child with autism spectrum disorder is likely to have a unique pattern of behavior and level of severity — from low functioning to high functioning.

Some children with autism spectrum disorder have difficulty learning, and some have signs of lower than normal intelligence. Other children with the disorder have normal to high intelligence — they learn quickly, yet have trouble communicating and applying what they know in everyday life and adjusting to social situations.

Because of the unique mixture of symptoms in each child, severity can sometimes be difficult to determine. It's generally based on the level of impairments and how they impact the ability to function.

Below are some common signs shown by people who have autism spectrum disorder.

Social communication and interaction

A child or adult with autism spectrum disorder may have problems with social interaction and communication skills, including any of these signs:

• Fails to respond to his or her name or appears not to hear you at times
• Resists cuddling and holding, and seems to prefer playing alone, retreating into his or her own world
• Has poor eye contact and lacks facial expression
• Doesn't speak or has delayed speech, or loses previous ability to say words or sentences
• Can't start a conversation or keep one going, or only starts one to make requests or label items
• Speaks with an abnormal tone or rhythm and may use a singsong voice or robot-like speech
• Repeats words or phrases verbatim, but doesn't understand how to use them
• Doesn't appear to understand simple questions or directions
• Doesn't express emotions or feelings and appears unaware of others' feelings
• Doesn't point at or bring objects to share interest
• Inappropriately approaches a social interaction by being passive, aggressive or disruptive
• Has difficulty recognizing nonverbal cues, such as interpreting other people's facial expressions, body postures or tone of voice

Patterns of behavior

A child or adult with autism spectrum disorder may have limited, repetitive patterns of behavior, interests or activities, including any of these signs:

• Performs repetitive movements, such as rocking, spinning or hand flapping
• Performs activities that could cause self-harm, such as biting or head-banging
• Develops specific routines or rituals and becomes disturbed at the slightest change
• Has problems with coordination or has odd movement patterns, such as clumsiness or walking on toes, and has odd, stiff or exaggerated body language
• Is fascinated by details of an object, such as the spinning wheels of a toy car, but doesn't understand the overall purpose or function of the object
• Is unusually sensitive to light, sound or touch, yet may be indifferent to pain or temperature
• Doesn't engage in imitative or make-believe play
• Fixates on an object or activity with abnormal intensity or focus
• Has specific food preferences, such as eating only a few foods, or refusing foods with a certain texture

As they mature, some children with autism spectrum disorder become more engaged with others and show fewer disturbances in behavior. Some, usually those with the least severe problems, eventually may lead normal or near-normal lives. Others, however, continue to have difficulty with language or social skills, and the teen years can bring worse behavioral and emotional problems.

When to see a doctor

Babies develop at their own pace, and many don't follow exact timelines found in some parenting books. But children with autism spectrum disorder usually show some signs of delayed development before age 2 years.

If you're concerned about your child's development or you suspect that your child may have autism spectrum disorder, discuss your concerns with your doctor. The symptoms associated with the disorder can also be linked with other developmental disorders.

Signs of autism spectrum disorder often appear early in development when there are obvious delays in language skills and social interactions. Your doctor may recommend developmental tests to identify if your child has delays in cognitive, language and social skills, if your child:

• Doesn't respond with a smile or happy expression by 6 months
• Doesn't mimic sounds or facial expressions by 9 months
• Doesn't babble or coo by 12 months
• Doesn't gesture — such as point or wave — by 14 months
• Doesn't say single words by 16 months
• Doesn't play "make-believe" or pretend by 18 months
• Doesn't say two-word phrases by 24 months
• Loses language skills or social skills at any age

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

From Mayo Clinic to your inbox

Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. Click here for an email preview.

Error Email field is required

Error Include a valid email address

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

Thank you for subscribing!

You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox.

Sorry something went wrong with your subscription

Please, try again in a couple of minutes

Autism spectrum disorder has no single known cause. Given the complexity of the disorder, and the fact that symptoms and severity vary, there are probably many causes. Both genetics and environment may play a role.

• Genetics. Several different genes appear to be involved in autism spectrum disorder. For some children, autism spectrum disorder can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For other children, genetic changes (mutations) may increase the risk of autism spectrum disorder. Still other genes may affect brain development or the way that brain cells communicate, or they may determine the severity of symptoms. Some genetic mutations seem to be inherited, while others occur spontaneously.
• Environmental factors. Researchers are currently exploring whether factors such as viral infections, medications or complications during pregnancy, or air pollutants play a role in triggering autism spectrum disorder.

No link between vaccines and autism spectrum disorder

One of the greatest controversies in autism spectrum disorder centers on whether a link exists between the disorder and childhood vaccines. Despite extensive research, no reliable study has shown a link between autism spectrum disorder and any vaccines. In fact, the original study that ignited the debate years ago has been retracted due to poor design and questionable research methods.

Avoiding childhood vaccinations can place your child and others in danger of catching and spreading serious diseases, including whooping cough (pertussis), measles or mumps.

Risk factors

The number of children diagnosed with autism spectrum disorder is rising. It's not clear whether this is due to better detection and reporting or a real increase in the number of cases, or both.

Autism spectrum disorder affects children of all races and nationalities, but certain factors increase a child's risk. These may include:

• Your child's sex. Boys are about four times more likely to develop autism spectrum disorder than girls are.
• Family history. Families who have one child with autism spectrum disorder have an increased risk of having another child with the disorder. It's also not uncommon for parents or relatives of a child with autism spectrum disorder to have minor problems with social or communication skills themselves or to engage in certain behaviors typical of the disorder.
• Other disorders. Children with certain medical conditions have a higher than normal risk of autism spectrum disorder or autism-like symptoms. Examples include fragile X syndrome, an inherited disorder that causes intellectual problems; tuberous sclerosis, a condition in which benign tumors develop in the brain; and Rett syndrome, a genetic condition occurring almost exclusively in girls, which causes slowing of head growth, intellectual disability and loss of purposeful hand use.
• Extremely preterm babies. Babies born before 26 weeks of gestation may have a greater risk of autism spectrum disorder.
• Parents' ages. There may be a connection between children born to older parents and autism spectrum disorder, but more research is necessary to establish this link.

Complications

Problems with social interactions, communication and behavior can lead to:

• Problems in school and with successful learning
• Employment problems
• Inability to live independently
• Social isolation
• Stress within the family
• Victimization and being bullied

More Information

• Autism spectrum disorder and digestive symptoms

There's no way to prevent autism spectrum disorder, but there are treatment options. Early diagnosis and intervention is most helpful and can improve behavior, skills and language development. However, intervention is helpful at any age. Though children usually don't outgrow autism spectrum disorder symptoms, they may learn to function well.

• Autism spectrum disorder (ASD). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/facts.html. Accessed April 4, 2017.
• Uno Y, et al. Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder. Vaccine. 2015;33:2511.
• Taylor LE, et al. Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies. Vaccine. 2014;32:3623.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Overview of management. https://www.uptodate.com/home. Accessed April 4, 2017.
• Autism spectrum disorder. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. Arlington, Va.: American Psychiatric Association; 2013. http://dsm.psychiatryonline.org. Accessed April 4, 2017.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Complementary and alternative therapies. https://www.uptodate.com/home. Accessed April 4, 2017.
• Augustyn M. Autism spectrum disorder: Terminology, epidemiology, and pathogenesis. https://www.uptodate.com/home. Accessed April 4, 2017.
• Bridgemohan C. Autism spectrum disorder: Surveillance and screening in primary care. https://www.uptodate.com/home. Accessed April 4, 2017.
• Levy SE, et al. Complementary and alternative medicine treatments for children with autism spectrum disorder. Child and Adolescent Psychiatric Clinics of North America. 2015;24:117.
• Brondino N, et al. Complementary and alternative therapies for autism spectrum disorder. Evidence-Based Complementary and Alternative Medicine. http://dx.doi.org/10.1155/2015/258589. Accessed April 4, 2017.
• Volkmar F, et al. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2014;53:237.
• Autism spectrum disorder (ASD). Eunice Kennedy Shriver National Institute of Child Health and Human Development. https://www.nichd.nih.gov/health/topics/autism/Pages/default.aspx. Accessed April 4, 2017.
• American Academy of Pediatrics policy statement: Sensory integration therapies for children with developmental and behavioral disorders. Pediatrics. 2012;129:1186.
• James S, et al. Chelation for autism spectrum disorder (ASD). Cochrane Database of Systematic Reviews. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010766.pub2/abstract;jsessionid=9467860F2028507DFC5B69615F622F78.f04t02. Accessed April 4, 2017.
• Van Schalkwyk GI, et al. Autism spectrum disorders: Challenges and opportunities for transition to adulthood. Child and Adolescent Psychiatric Clinics of North America. 2017;26:329.
• Autism. Natural Medicines. https://naturalmedicines.therapeuticresearch.com. Accessed April 4, 2017.
• Autism: Beware of potentially dangerous therapies and products. U.S. Food and Drug Administration. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm394757.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed May 19, 2017.
• Drutz JE. Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor. https://www.uptodate.com/home. Accessed May 19, 2017.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Behavioral and educational interventions. https://www.uptodate.com/home. Accessed May 19, 2017.
• Huebner AR (expert opinion). Mayo Clinic, Rochester, Minn. June 7, 2017.

Associated Procedures

• Cognitive behavioral therapy

News from Mayo Clinic

• 10 significant studies from Mayo Clinic's Center for Individualized Medicine in 2023 Dec. 30, 2023, 12:00 p.m. CDT
• Mayo Clinic 'mini-brain' study reveals possible key link to autism spectrum disorder Aug. 10, 2023, 04:00 p.m. CDT
• Symptoms & causes
• Diagnosis & treatment
• Doctors & departments

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book

Make twice the impact

Your gift can go twice as far to advance cancer research and care!

Transforming the understanding and treatment of mental illnesses.

Información en español

Celebrating 75 Years! Learn More >>

• Health Topics
• Brochures and Fact Sheets
• Help for Mental Illnesses
• Clinical Trials

Autism Spectrum Disorder

What is asd.

Autism spectrum disorder (ASD) is a neurological and developmental disorder that affects how people interact with others, communicate, learn, and behave. Although autism can be diagnosed at any age, it is described as a “developmental disorder” because symptoms generally appear in the first 2 years of life.

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) , a guide created by the American Psychiatric Association that health care providers use to diagnose mental disorders, people with ASD often have:

• Difficulty with communication and interaction with other people
• Restricted interests and repetitive behaviors
• Symptoms that affect their ability to function in school, work, and other areas of life

Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience.

People of all genders, races, ethnicities, and economic backgrounds can be diagnosed with ASD. Although ASD can be a lifelong disorder, treatments and services can improve a person’s symptoms and daily functioning. The American Academy of Pediatrics recommends that all children receive screening for autism. Caregivers should talk to their child’s health care provider about ASD screening or evaluation.

What are the signs and symptoms of ASD?

The list below gives some examples of common types of behaviors in people diagnosed with ASD. Not all people with ASD will have all behaviors, but most will have several of the behaviors listed below.

Social communication / interaction behaviors may include:

• Making little or inconsistent eye contact
• Appearing not to look at or listen to people who are talking
• Infrequently sharing interest, emotion, or enjoyment of objects or activities (including infrequent pointing at or showing things to others)
• Not responding or being slow to respond to one’s name or to other verbal bids for attention
• Having difficulties with the back and forth of conversation
• Often talking at length about a favorite subject without noticing that others are not interested or without giving others a chance to respond
• Displaying facial expressions, movements, and gestures that do not match what is being said
• Having an unusual tone of voice that may sound sing-song or flat and robot-like
• Having trouble understanding another person’s point of view or being unable to predict or understand other people’s actions
• Difficulties adjusting behaviors to social situations
• Difficulties sharing in imaginative play or in making friends

Restrictive / repetitive behaviors may include:

• Repeating certain behaviors or having unusual behaviors, such as repeating words or phrases (a behavior called echolalia)
• Having a lasting intense interest in specific topics, such as numbers, details, or facts
• Showing overly focused interests, such as with moving objects or parts of objects
• Becoming upset by slight changes in a routine and having difficulty with transitions
• Being more sensitive or less sensitive than other people to sensory input, such as light, sound, clothing, or temperature

People with ASD may also experience sleep problems and irritability.

People on the autism spectrum also may have many strengths, including:

• Being able to learn things in detail and remember information for long periods of time
• Being strong visual and auditory learners
• Excelling in math, science, music, or art

What are the causes and risk factors for ASD?

Researchers don’t know the primary causes of ASD, but studies suggest that a person’s genes can act together with aspects of their environment to affect development in ways that lead to ASD. Some factors that are associated with an increased likelihood of developing ASD include:

• Having a sibling with ASD
• Having older parents
• Having certain genetic conditions (such as Down syndrome or Fragile X syndrome)
• Having a very low birth weight

How is ASD diagnosed?

Health care providers diagnose ASD by evaluating a person’s behavior and development. ASD can usually be reliably diagnosed by age 2. It is important to seek an evaluation as soon as possible. The earlier ASD is diagnosed, the sooner treatments and services can begin.

Diagnosis in young children

Diagnosis in young children is often a two-stage process.

Stage 1: General developmental screening during well-child checkups

Every child should receive well-child check-ups with a pediatrician or an early childhood health care provider. The American Academy of Pediatrics recommends that all children receive screening for developmental delays at their 9-, 18-, and 24- or 30-month well-child visits, with specific autism screenings at their 18- and 24-month well-child visits. A child may receive additional screening if they have a higher likelihood of ASD or developmental problems. Children with a higher likelihood of ASD include those who have a family member with ASD, show some behaviors that are typical of ASD, have older parents, have certain genetic conditions, or who had a very low birth weight.

Considering caregivers’ experiences and concerns is an important part of the screening process for young children. The health care provider may ask questions about the child’s behaviors and evaluate those answers in combination with information from ASD screening tools and clinical observations of the child. Read more about screening instruments   on the Centers for Disease Control and Prevention (CDC) website.

If a child shows developmental differences in behavior or functioning during this screening process, the health care provider may refer the child for additional evaluation.

Stage 2: Additional diagnostic evaluation

It is important to accurately detect and diagnose children with ASD as early as possible, as this will shed light on their unique strengths and challenges. Early detection also can help caregivers determine which services, educational programs, and behavioral therapies are most likely to be helpful for their child.

A team of health care providers who have experience diagnosing ASD will conduct the diagnostic evaluation. This team may include child neurologists, developmental pediatricians, speech-language pathologists, child psychologists and psychiatrists, educational specialists, and occupational therapists.

The diagnostic evaluation is likely to include:

• Medical and neurological examinations
• Assessment of the child’s cognitive abilities
• Assessment of the child’s language abilities
• Observation of the child’s behavior
• An in-depth conversation with the child’s caregivers about the child’s behavior and development
• Assessment of age-appropriate skills needed to complete daily activities independently, such as eating, dressing, and toileting

Because ASD is a complex disorder that sometimes occurs with other illnesses or learning disorders, the comprehensive evaluation may include:

• Blood tests
• Hearing test

The evaluation may lead to a formal diagnosis and recommendations for treatment.

Diagnosis in older children and adolescents

Caregivers and teachers are often the first to recognize ASD symptoms in older children and adolescents who attend school. The school’s special education team may perform an initial evaluation and then recommend that a child undergo additional evaluation with their primary health care provider or a health care provider who specialize in ASD.

A child’s caregivers may talk with these health care providers about their child’s social difficulties, including problems with subtle communication. For example, some children may have problems understanding tone of voice, facial expressions, or body language. Older children and adolescents may have trouble understanding figures of speech, humor, or sarcasm. They also may have trouble forming friendships with peers.

Diagnosis in adults

Diagnosing ASD in adults is often more difficult than diagnosing ASD in children. In adults, some ASD symptoms can overlap with symptoms of other mental health disorders, such as anxiety disorder or attention-deficit/hyperactivity disorder (ADHD).

Adults who notice signs of ASD should talk with a health care provider and ask for a referral for an ASD evaluation. Although evaluation for ASD in adults is still being refined, adults may be referred to a neuropsychologist, psychologist, or psychiatrist who has experience with ASD. The expert will ask about:

• Social interaction and communication challenges
• Sensory issues
• Repetitive behaviors
• Restricted interests

The evaluation also may include a conversation with caregivers or other family members to learn about the person’s early developmental history, which can help ensure an accurate diagnosis.

Receiving a correct diagnosis of ASD as an adult can help a person understand past challenges, identify personal strengths, and find the right kind of help. Studies are underway to determine the types of services and supports that are most helpful for improving the functioning and community integration of autistic transition-age youth and adults.

What treatment options are available for ASD?

Treatment for ASD should begin as soon as possible after diagnosis. Early treatment for ASD is important as proper care and services can reduce individuals’ difficulties while helping them build on their strengths and learn new skills.

People with ASD may face a wide range of issues, which means that there is no single best treatment for ASD. Working closely with a health care provider is an important part of finding the right combination of treatment and services.

A health care provider may prescribe medication to treat specific symptoms. With medication, a person with ASD may have fewer problems with:

• Irritability
• Repetitive behavior
• Hyperactivity
• Attention problems
• Anxiety and depression

Read more about the latest medication warnings, patient medication guides, and information on newly approved medications at the Food and Drug Administration (FDA) website  .

Behavioral, psychological, and educational interventions

People with ASD may be referred to a health care provider who specializes in providing behavioral, psychological, educational, or skill-building interventions. These programs are often highly structured and intensive, and they may involve caregivers, siblings, and other family members. These programs may help people with ASD:

• Learn social, communication, and language skills
• Reduce behaviors that interfere with daily functioning
• Increase or build upon strengths
• Learn life skills for living independently

Other resources

Many services, programs, and other resources are available to help people with ASD. Here are some tips for finding these additional services:

• Contact your health care provider, local health department, school, or autism advocacy group to learn about special programs or local resources.
• Find an autism support group. Sharing information and experiences can help people with ASD and their caregivers learn about treatment options and ASD-related programs.
• Record conversations and meetings with health care providers and teachers. This information may help when it’s time to decide which programs and services are appropriate.
• Keep copies of health care reports and evaluations. This information may help people with ASD qualify for special programs.

How can I find a clinical trial for ASD?

Clinical trials are research studies that look at new ways to prevent, detect, or treat diseases and conditions. The goal of clinical trials is to determine if a new test or treatment works and is safe. Although individuals may benefit from being part of a clinical trial, participants should be aware that the primary purpose of a clinical trial is to gain new scientific knowledge so that others may be better helped in the future.

Researchers at NIMH and around the country conduct many studies with patients and healthy volunteers. We have new and better treatment options today because of what clinical trials uncovered years ago. Be part of tomorrow’s medical breakthroughs. Talk to your health care provider about clinical trials, their benefits and risks, and whether one is right for you.

To learn more or find a study, visit:

• NIMH’s Clinical Trials webpage : Information about participating in clinical trials
• Clinicaltrials.gov: Current Studies on ASD  : List of clinical trials funded by the National Institutes of Health (NIH) being conducted across the country

Where can I learn more about ASD?

Free brochures and shareable resources.

• Autism Spectrum Disorder : This brochure provides information about the symptoms, diagnosis, and treatment of ASD. Also available  en español .
• Digital Shareables on Autism Spectrum Disorder : Help support ASD awareness and education in your community. Use these digital resources, including graphics and messages, to spread the word about ASD.

Federal resources

• Eunice Kennedy Shriver National Institute of Child Health and Human Development  
• National Institute of Neurological Disorders and Stroke  
• National Institute on Deafness and Other Communication Disorders  
• Centers for Disease Control and Prevention   (CDC)
• Interagency Autism Coordinating Committee  
• MedlinePlus   (also available en español  )

Research and statistics

• Science News About Autism Spectrum Disorder : This NIMH webpage provides press releases and announcements about ASD.
• Research Program on Autism Spectrum Disorders : This NIMH program supports research focused on the characterization, pathophysiology, treatment, and outcomes of ASD and related disorders.
• Statistics: Autism Spectrum Disorder : This NIMH webpage provides information on the prevalence of ASD in the U.S.
• Data & Statistics on Autism Spectrum Disorder   : This CDC webpage provides data, statistics, and tools about prevalence and demographic characteristics of ASD.
• Autism and Developmental Disabilities Monitoring (ADDM) Network   : This CDC-funded program collects data to better understand the population of children with ASD.
• Biomarkers Consortium - The Autism Biomarkers Consortium for Clinical Trials (ABC-CT)   : This Foundation for the National Institutes of Health project seeks to establish biomarkers to improve treatments for children with ASD.

Last Reviewed:  February 2024

Unless otherwise specified, the information on our website and in our publications is in the public domain and may be reused or copied without permission. However, you may not reuse or copy images. Please cite the National Institute of Mental Health as the source. Read our copyright policy to learn more about our guidelines for reusing NIMH content.

What Causes Autism?

Reviewed by Psychology Today Staff

The unsatisfying answer to this question is that scientists still don’t fully grasp what leads to autism. Rather than a single gene or lifestyle trend, autism is the result of complex interactions between many different factors.

Genetics contribute more to the condition than do environmental factors. Autism is highly heritable, and people who have a sibling with autism are more likely to have autism themselves. People are more likely to have autism if they have related genetic disorders, such as fragile X syndrome, Rett syndrome, and tuberous sclerosis.

Autism is also more likely due to a number of environmental factors, such as maternal infection, diabetes, high blood pressure, and older paternal age at conception. Pinning down the connection to other elements of the environment, such as air pollution, has proven more difficult.

The number of children diagnosed with the disorder has risen dramatically since the 1960s. Experts believe that much of the change can be attributed to changes in diagnostic criteria and greater awareness among clinicians and the general public.

On This Page

• Is autism genetic?
• What are genetic risk factors for autism?
• Do environmental factors cause autism?
• Do vaccines cause autism?
• What prenatal factors increase the risk of autism?
• What is causing rates of autism to increase?
• Are boys more likely than girls to have autism?
• Why are boys more likely to have autism?

Yes, genes play an important role in autism. The heritability of autism is estimated to be around 80 percent. This means that if one identical twin has autism, the other twin would have an 80 percent chance of developing autism. In the case of fraternal twins, who share half rather than all of their DNA, the second twin has a 40 percent chance of developing autism. People whose siblings have the condition are also more likely to develop it. People with genetic disorders such as fragile X syndrome, Rett syndrome, or tuberculosis sclerosis are also more likely to have autism, according to the CDC.

Dozens of genes are now known to correlate strongly with autism, and hundreds more have smaller connections. Genetic differences can be inherited through a parent’s DNA or they could spontaneously occur in the sperm, egg, or embryo. A person who is said to have risk factors often has a first degree relative with an autism spectrum disorder, but it is impossible to quantify the risk at this time.

It is important to understand that having genetic risk factors for autism does not mean that a person will necessarily go on to develop the condition.

Several environmental factors increase the risk of autism, and they center around experiences in the pregnancy or infancy that may influence brain development. Premature birth and low birth weight raise the risk of autism, as do diabetes, high blood pressure, and infection during pregnancy. Having an older father is also a risk factor, likely because the chance of spontaneous genetic mutations increases with age.

There is some evidence of a correlation between exposure to air pollution during pregnancy or early childhood and the onset of autism. However, researchers are still working to understand this relationship. Pinning down the connection between autism and any single environmental factor is difficult because it’s nearly impossible to isolate—there are so many variables at play.

No. There is no connection between vaccines and autism. Vaccines are powerful tools that doctors and parents rely on to protect children from dangerous illnesses.

The specious claim emerged from a paper published in the journal The Lancet in 2013 by disgraced physician Andrew Wakefield, who claimed that a preservative in vaccines called Thimerosal caused autism. The paper was deeply flawed and later retracted by the journal that published it. Rigorous research has continued to find no connection between the two.

Taking the medications thalidomide or valproic acid during pregnancy can raise the risk of autism, according to the CDC. There is some research that antidepressant use during pregnancy increases the risk of autism, but that research is not yet definitive.

Other elements linked to a higher likelihood of developing autism include having an infection, autoimmune disease, diabetes, or high blood pressure during pregnancy. This may be due to the manner in which inflammation and the immune response influence the developing fetus. There also seem to be correlations between autism risk and pregnancies that are less than a year apart.

Some evidence indicates taking prenatal vitamins containing folic acid, vitamin B-9, and vitamin D may offer some protection and reduce the likelihood of autism.

The prevalence of autism has continued to rise over the past few decades. Today, 1 in 54 children are estimated to have autism, according to the CDC. Research suggests that this surge is not due to changes in the genetic and environmental factors that contribute to the condition. The rising prevalence is instead likely due to changes in the diagnostic criteria and greater awareness of autism and its symptoms.

Clinicians diagnose mental health conditions based on criteria delineated in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The pre-2013 version, the DSM-IV, contained three categories: autistic disorder, Asperger’s disorder, and pervasive developmental disorder not otherwise specified. The current iteration, the DSM-5, replaces those categories with one overarching diagnosis: autism spectrum disorder. The current definition of autism is no longer reserved for the most extreme cases; it embraces subtler ones as well.

Autism occurs 4 times more often in boys than in girls. This asymmetry may be due to a combination of biological and diagnostic forces.

From a biological perspective, women with autism have more family members with the condition than men and have more genetic mutations. These findings and others form the basis for the “female protective effect,” a theory that women possess some form of biological protection against autism.

The “extreme male brain,” was proposed by British scientist Simon-Baron Cohen. People with autism have an extreme form of the male brain, the theory goes, as men tend to be drawn to systems and efficiency while women excel at empathy and reading emotions. Others have pushed back that underlying biological differences between the sexes could not be large enough to account for the condition and the idea hasn’t been replicated by other scholars.

From a diagnostic perspective, clinicians may be more aware of the condition in boys and therefore identify it more readily. Additionally, the instruments to screen and diagnose the conditions were created and validated on males.

Although autism occurs more frequently in boys, many girls and women have the condition. The symptoms may present differently, and they may learn to camouflage the condition. Women may be overlooked or misdiagnosed as a result, but finally receiving a diagnosis has the potential to be life-changing.

Does your child have autism? Need inspiration? Learn the triumphant story of the ASD Band.

There may be important nuances in disordered eating among neurodivergent people, including when disordered eating is considered a clinical concern.

It is important that caregivers and educators not make inferences about the social motivation of children with autism from how they perceive their nonverbal cues.

Mindstorms like meltdowns and shutdowns are common experiences, especially for neurodivergent people. Here are five strategies for getting through one or providing support.

A Personal Perspective: Here's a card-based metaphor to explore autism, bottom-up processing, and intense world theory.

Employee experience, or EX, matters more than ever. By embracing how we all think differently, EX can be transformed for everybody.

The existence of savants pushes us to ask whether it is possible for neurotypical individuals to tap into extraordinary abilities.

"Cyberball" experiments can help children and parents better understand and utilize cognitive-behavior therapy focused on promoting emotional self-regulation.

A Personal Perspective: Autism Acceptance Month is an opportunity to celebrate our differences and recognize the contribution that neurodivergent individuals make to the world.

Celebrating neurodiversity is not just for schools and therapists. It's about all of us coming together as a community to appreciate all ways of experiencing the world and showing kindness.

• Find a Therapist
• Find a Treatment Center
• Find a Psychiatrist
• Find a Support Group
• Find Teletherapy
• United States
• Brooklyn, NY
• Chicago, IL
• Houston, TX
• Los Angeles, CA
• New York, NY
• Portland, OR
• San Diego, CA
• San Francisco, CA
• Seattle, WA
• Washington, DC
• Asperger's
• Bipolar Disorder
• Chronic Pain
• Eating Disorders
• Passive Aggression
• Personality
• Goal Setting
• Positive Psychology
• Stopping Smoking
• Low Sexual Desire
• Relationships
• Child Development
• Therapy Center NEW
• Diagnosis Dictionary
• Types of Therapy

Understanding what emotional intelligence looks like and the steps needed to improve it could light a path to a more emotionally adept world.

• Coronavirus Disease 2019
• Affective Forecasting
• Neuroscience

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Systematic Review
• Open access
• Published: 15 June 2022

Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses

• Shuang Qiu 1 ,
• Yingjia Qiu 2 ,
• Yan Li 3 &
• Xianling Cong   ORCID: orcid.org/0000-0002-5790-4188 1  

Translational Psychiatry volume  12 , Article number:  249 ( 2022 ) Cite this article

16k Accesses

22 Citations

9 Altmetric

Metrics details

• Autism spectrum disorders

Autism spectrum disorder (ASD) is a class of neurodevelopmental conditions with a large epidemiological and societal impact worldwide. To date, numerous studies have investigated the associations between genetic variants and ASD risk. To provide a robust synthesis of published evidence of candidate gene studies for ASD, we performed an umbrella review (UR) of meta-analyses of genetic studies for ASD (PROSPERO registration number: CRD42021221868). We systematically searched eight English and Chinese databases from inception to March 31, 2022. Reviewing of eligibility, data extraction, and quality assessment were performed by two authors. In total, 28 of 5062 retrieved articles were analyzed, which investigated a combined 41 single nucleotide polymorphisms (SNPs) of nine candidate genes. Overall, 12 significant SNPs of CNTNAP2 , MTHFR , OXTR , SLC25A12 , and VDR were identified, of which associations with suggestive evidence included the C677T polymorphism of MTHFR (under allelic, dominant, and heterozygote models) and the rs731236 polymorphism of VDR (under allelic and homozygote models). Associations with weak evidence included the rs2710102 polymorphism of CNTNAP2 (under allelic, homozygote, and recessive models), the rs7794745 polymorphism of CNTNAP2 (under dominant and heterozygote models), the C677T polymorphism of MTHFR (under homozygote model), and the rs731236 polymorphism of VDR (under dominant and recessive models). Our UR summarizes research evidence on the genetics of ASD and provides a broad and detailed overview of risk genes for ASD. The rs2710102 and rs7794745 polymorphisms of CNTNAP2 , C677T polymorphism of MTHFR , and rs731236 polymorphism of VDR may confer ASD risks. This study will provide clinicians and healthcare decision-makers with evidence-based information about the most salient candidate genes relevant to ASD and recommendations for future treatment, prevention, and research.

Similar content being viewed by others

Exome-wide analysis implicates rare protein-altering variants in human handedness

Dick Schijven, Sourena Soheili-Nezhad, … Clyde Francks

Genome-wide association studies

Emil Uffelmann, Qin Qin Huang, … Danielle Posthuma

The serotonin theory of depression: a systematic umbrella review of the evidence

Joanna Moncrieff, Ruth E. Cooper, … Mark A. Horowitz

Introduction

Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions characterized by early-onset dysfunctions in communication, impairments in social interaction, and repetitive and stereotyped behaviors and interests [ 1 ]. Patients develop ASD-related symptoms when they are 12−18 months of age, and diagnosis is generally made at the age of 2 years [ 2 ]. In 2010, 52 million people had been diagnosed with ASD worldwide, which was equivalent to a population prevalence of 7.6 per 1000 or 1 in 132 persons [ 3 ]. ASD is the leading cause of disability in children under 5 years, and people with ASD may require high levels of support, which is costly and thus leads to substantial economic, emotional, and physical burdens on affected families [ 3 ].

Due to the lack of clinical and epidemiological evidence for an ASD cure, researchers have focused on better understanding ASD and advancing risk prediction and prevention [ 3 ]. The causes of ASD are complex and multifactorial, with several associated genes and environmental risk factors [ 4 ]. A previous umbrella review (UR) of environmental risk factors for ASD showed that several maternal factors, including advanced age (≥35 years), chronic hypertension, preeclampsia, gestational hypertension, and being overweight before or during pregnancy, were significantly associated with ASD risk, without any signs of bias [ 5 , 6 ]. Accumulating twin- and family based studies further indicate that genetic factors play critical roles in ASD, such that the concordance rate among monozygotic twins is higher (60–90%) than that among dizygotic twins (0–30%) [ 7 , 8 ]. The heritability of ASD has been estimated to be 50%, indicating that genetic factors are the main contributors to the etiology of ASD [ 8 ].

To date, numerous studies investigating the association between genetic variants and ASD risk have been published [ 9 , 10 , 11 ]. Most of these studies focused on identifying single nucleotide polymorphisms (SNPs) of candidate genes associated with ASD risk. However, these SNP studies had small sample sizes and, therefore, low statistical power to demonstrate statistically significant effects of low-risk susceptibility genes, leading to inconsistent conclusions. Although meta-analyses have been conducted to resolve this problem, single SNPs or genes have usually been investigated.

An UR collects and evaluates multiple systematic reviews and meta-analyses conducted on a specific research topic, provides a robust synthesis of published evidence, and considers the importance of effects found over time [ 12 ]. In addition, the results of UR studies may increase the predictive power with more precise estimates [ 13 ]. Thus, we aimed to perform an UR study of all the systematic reviews and meta-analyses that have been published, assessing candidate genes associated with ASD risk. This study will provide clinicians and healthcare decision-makers with evidence-based information about candidate genes of ASD and recommendations for future prevention and research in less time than would otherwise be required to locate and examine all relevant research individually.

Literature search strategy and eligibility criteria

We systematically searched the PubMed, EMBASE, PsycINFO, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Sinomed, and Wanfang databases from inception to March 31, 2022. The databases were searched using the following strategy: (autis* [All Fields] OR autism* [All Fields] OR autistic* [All Fields] OR ASD [All Fields] OR autism spectrum disorder* [All Fields] OR PDD-NOS [All Fields] OR PDDNOS [All Fields] OR unspecified PDD [All Fields] OR PDD [All Fields] OR pervasive developmental disorder* [All Fields] OR pervasive developmental disorder not otherwise specified [All Fields] OR Asperger* [All Fields] OR Asperger* syndrome [All Fields]) AND (gene* [All Fields] OR genom* [All Fields]) AND (systematic review [All Fields] OR meta-analysis [All Fields]). Authors S. Qiu and Y. Qiu independently conducted literature searches for potential articles included in this review. The references of the relevant articles were manually searched to identify and incorporate eligible studies.

We included meta-analyses of family based and case-control studies that examined associations between ASD and potential risk genes. We only included meta-analyses that reported either effect estimates of individual study or the data necessary to calculate these estimates. We excluded meta-analyses if (1) risk genes were used for screening, diagnostic, or prognostic purposes; (2) a study examined ASD as a risk factor for other medical conditions; (3) a study included fewer than three original studies investigating the association between risk genes and ASD; and (4) a study with missing information after the corresponding author, whom we contacted through email, failed to provide the required information. All articles retrieved were first organized in the reference manager software (Endnote 9, Clarivate Analytics, New York, NY, USA), and duplicates were deleted. S. Qiu and Y. Qiu chose eligible articles by screening the titles, abstracts, and full article texts independently. Disagreements were resolved through a discussion with a third investigator (Y. Li) until a consensus was reached.

Data extraction and quality assessment

From each eligible meta-analysis, we extracted the first author, publication year, genetic risk factors examined, number of studies, number of ASD cases and participants, study-specific relative risk estimates (odds ratio [ OR ]) with the corresponding 95% confidence interval ( CI ), sample size of cases and controls, genotype and allele counts, and individual study designs (case-control, family based or mixed [case-control and family based]). We used the ‘assessment of multiple systematic reviews’ tool, consisting of 11 items, to assess the methodological quality of the meta-analyses [ 14 ]. Data extraction and quality assessment were independently conducted by S. Qiu and Y. Qiu. Disagreements were resolved via a discussion with a third investigator (Y. Li) until a consensus was reached.

Data analysis

In agreement with previous URs, we performed a statistical analysis using a series of tests that were previously developed and reproduced [ 13 , 15 , 16 ]. If more than one meta-analysis on the same research question was eligible, the most recent meta-analysis was retained for the main analysis. For each eligible meta-analysis, we calculated the summary-effect size with 95% CI [ 17 ]. We also calculated the 95% prediction interval ( PI ) to explain the between-study heterogeneity and to assess the uncertainty of a new study [ 18 , 19 ]. Heterogeneity between studies was assessed using the Chi-squared test based Q-statistic and quantified using the I 2 -statistic [ 20 , 21 ]. If there was no substantial statistical heterogeneity ( P  > 0.10, I 2  ≤ 50%), data were pooled using a fixed-effect model; otherwise, heterogeneity was evaluated using a random-effect model [ 22 ]. The Hardy–Weinberg equilibrium (HWE) of meta-analyses in the control group was analyzed using Chi-squared tests. Additionally, small-study effects were evaluated using Egger’s regression asymmetry test. P -values < 0.10 were considered to indicate the presence of small-study effects [ 23 , 24 ]. The Chi-squared test was used to assess the presence of excess significance, which evaluated whether the observed number of studies with significant results ( P  < 0.05) was greater than the expected number [ 22 , 25 ]. All statistical analyses were performed using RStudio 3.6.2. Statistical significance was set at P  < 0.05, except where otherwise specified.

Determining the credibility of evidence

In line with previous URs, we categorized the strength of the evidence of risk genes for ASD into five levels: convincing (class I), highly suggestive (class II), suggestive (class III), weak (class IV), and not significant [ 5 , 26 , 27 , 28 ]. Criteria for the level of evidence included the number of ASD cases, P -values by random effects model, small-study effects, excess significance bias, heterogeneity ( I² ), and 95% CI .

This review was prospectively registered with PROSPERO (registration number: CRD42021221868).

Description of eligible meta-analyses

A total of 5062 articles were identified through an initial search. After removing duplicates, the titles and abstracts of 3182 articles were screened for eligibility. Of the remaining 66 articles that were reviewed in full, 28 eligible articles were selected for data extraction (Fig. 1 ).

Flow chart of literature identification and selection.

The characteristics of the selected studies are presented in Table 1 . Of the 28 included reviews, eight were on methylenetetrahydrofolate reductase ( MTHFR ) [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]; four each on solute carrier family 6 member 4 ( SLC6A4 ) [ 37 , 38 , 39 , 40 ] and contactin associated protein 2 ( CNTNAP2 ) [ 41 , 42 , 43 , 44 ]; three each on oxytocin receptor ( OXTR ) [ 45 , 46 , 47 ] and reelin ( RELN ) [ 48 , 49 , 50 ]; two each on gamma-aminobutyric acid type A receptor subunit beta3 ( GABRB3 ) [ 51 , 52 ], solute carrier family 25 member 12 ( SLC25A12 ) [ 53 , 54 ], and vitamin D receptor ( VDR ) [ 55 , 56 ]; and one on catechol-o-methyltransferase ( COMT ) [ 39 ] (one meta-analysis was on both COMT and SLC6A4 ). These studies were published from 2008 to 2021 and considered the associations between 41 SNPs in nine candidate genes and ASD risk. For quality assessment, 22 articles that scored 5−8 were rated as ‘moderate quality’, and six that scored < 5 were rated as ‘low quality’. Seventeen studies (60.7%) performed the HWE check (Table 1 ). With respect to the study design, 14 (64.3%) studies synthesized case-control studies, two (7.1%) included family based studies, and eight (28.6%) used both case-control and family based studies (Table 1 ).

Summary-effect sizes and significant findings

The results of the associations between the 41 SNPs and ASD risks reported in the meta-analyses are presented in Table 2 under five different genetic models: allelic model (mutant allele vs. wild-type allele), dominant model (mutant homozygote + heterozygote vs. wild-type homozygote), heterozygote model (heterozygote vs. wild-type homozygote), homozygote model (mutant homozygote vs. wild-type homozygote), and recessive model (mutant homozygote vs. wild-type homozygote + heterozygote).

Only one meta-analysis on the rs2710102 polymorphism of CNTNAP2 showed that the polymorphism was associated with ASD susceptibility in allelic, homozygote, and recessive models [ 44 ]. This meta-analysis also found that the rs7794745 polymorphism of CNTNAP2 was associated with an increased risk of ASD in dominant and heterozygote models [ 44 ].

All four meta-analyses reported no significant association between the A1298C polymorphism of MTHFR and ASD risk. All eight meta-analyses on the C677T polymorphism of MTHFR showed that the polymorphism was associated with ASD susceptibility in allelic and heterozygote models [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Seven meta-analyses found that the C677T polymorphism was associated with an increased risk of ASD in dominant [ 29 , 31 , 32 , 33 , 34 , 35 , 36 ] and homozygote [ 29 , 30 , 31 , 33 , 34 , 35 , 36 ] models. Five meta-analyses found that the C677T polymorphism was associated with an increased risk of ASD in the recessive model [ 29 , 30 , 31 , 33 , 34 ].

For OXTR , 19 SNPs were summarized. LoParo et al. [ 45 ] found that the mutant allele of rs2268491, wild-type allele of rs237887, and mutant allele of rs7632287 were risk-inducing SNPs of ASD. In addition, Kranz et al. [ 46 ] found that the mutant allele of rs237889 was associated with ASD risk.

Regarding SLC25A12 , both Aoki et al. [ 53 ] and Liu et al. [ 54 ] found that the mutant alleles of rs2056202 and rs2292813 significantly increased ASD risk in family-based and mixed studies. We excluded the results of the associations between rs2292813 and ASD risk based on the case-control design reported by Liu et al. [ 54 ], as the authors included only two case–control studies.

Sun et al. [ 55 ] found that the rs2228570 polymorphism of VDR was associated with an increased ASD risk in homozygote and recessive models, while Yang et al. [ 56 ] did not find significant associations in any genetic model. Both authors [ 55 , 56 ] found that the rs731236 polymorphism of VDR was significantly associated with ASD risk in allelic, homozygote, and recessive models. Sun et al. [ 55 ] found that the rs731236 polymorphism was significantly associated with ASD risk in the dominant model. Both Sun et al. [ 55 ] and Yang et al. [ 56 ] found that the mutant allele of rs7975232 of VDR was significantly associated with a decreased ASD risk (Table 2 ). There were no significant SNPs in COMT , GABRB3 , RELN , and SLC6A4 .

When more than one meta-analysis on the same research question was eligible, the most recent one was retained for the main analysis. After comparing the publication year and sample size of each meta-analysis, 11 meta-analyses were retained for further analysis, of which two each study were on RELN and MTHFR , and one each was on CNTNAP2 , COMT , GABRB3 , OXTR , SLC25A12 , SLC6A4 , and VDR . We extracted the allele and genotype frequencies of each SNP in case and control groups from the original research for further analysis. However, the allele and genotype frequencies of some SNPs in the compared groups could not be extracted from the original research that did not contain the information, and we could not obtain this information from the corresponding authors of the studies. Finally, we analyzed the data of 20 SNPs with allele frequencies in 10 meta-analyses from 117 original studies and 16 SNPs with genotype frequencies in eight meta-analyses from 101 original studies. Associations were measured using five different genetic models (Tables 3 , 4 ).

We found that the rs2710102 polymorphism of CNTNAP2 was associated with a decreased ASD risk in the allelic ( OR  = 0.849, 95% CI  = 0.734–0.981, P  = 0.0263), homozygote ( OR  = 0.668, 95% CI  = 0.470–0.950, P  = 0.0248), and recessive ( OR  = 0.715, 95% CI  = 0.563–0.909, P  = 0.0062) models. In addition, we found that the mutant allele of rs7794745 ( CNTNAP2 ) increased ASD risk based on the dominant ( OR  = 1.300, 95% CI  = 1.109–1.523, P  = 0.0012) and heterozygote ( OR  = 1.275, 95% CI  = 1.081–1.504, P  = 0.0039) models. The C677T polymorphism of MTHFR was associated with an increased ASD risk in the allelic ( OR  = 1.799, 95% CI  = 1.303–2.483, P  = 0.0004), dominant ( OR  = 1.959, 95% CI  = 1.402–2.738, P  < 0.0001), heterozygote ( OR  = 1.767, 95% CI  = 1.343–2.330, P  < 0.0001), and homozygote ( OR  = 1.795, 95% CI  = 1.158–2.782, P  = 0.0089) models. The rs607755 polymorphism of RELN was associated with an increased ASD risk in the allelic ( OR  = 1.316, 95% CI  = 1.029–1.683, P  = 0.0284), dominant ( OR  = 1.520, 95% CI  = 1.061–2.178, P  = 0.0226), heterozygote ( OR  = 1.483, 95% CI  = 1.016–2.165, P  = 0.0411), and homozygote ( OR  = 1.816, 95% CI  = 1.051–3.136, P  = 0.0324) models. The rs731236 polymorphism of VDR was associated with an increased ASD risk in the allelic ( OR  = 1.297, 95% CI  = 1.125–1.494, P  = 0.0003), dominant ( OR  = 1.304, 95% CI  = 1.082–1.571, P  = 0.0053), homozygote ( OR  = 1.741, 95% CI  = 1.258–2.409, P  = 0.0008), and recessive ( OR  = 1.613, 95% CI  = 1.187–2.190, P  = 0.0022) models. In addition, we found that the mutant allele of rs7975232 ( VDR ) decreased ASD risk ( OR  = 0.823, 95% CI  = 0.681–0.993, P  = 0.0425) based on the allelic model. There was no significant association between the other SNPs and ASD risk (all P  > 0.05; Table 4 ).

As for the results of PI , the null value was excluded in only four SNPs of rs2710102 ( CNTNAP2 ) under the allelic, homozygote, and recessive models; rs7794745 ( CNTNAP2 ) under the heterozygote model; rs607755 ( RELN ) and rs731236 ( VDR ) under the allelic and homozygote models (Table 4 ). When evaluating small-study effects using Egger’s regression asymmetry test, evidence for statistically significant small-study effects in the meta-analyses was identified in some SNPs. Supporting evidence included a meta-analysis on A1298C ( MTHFR ) under the allelic, dominant, and heterozygote models; a meta-analysis on C677T ( MTHFR ) under the five genetic models; a meta-analysis on rs20317 ( GABRB3 ) under the dominant and heterozygote models; one each on rs736707 ( RELN ) and rs1544410 ( VDR ) under the recessive and allelic models, respectively; and three meta-analyses on rs607755 ( RELN ), 5-HTTLPR ( SLC6A4 ), and rs7975232 ( VDR ) under the heterozygote model ( P  < 0.10).

Hints of excess-statistical-significance bias were observed in rs2710102 ( CNTNAP2 ) under the allelic, homozygote, and recessive models; rs4680 ( COMT ) under the allelic model; rs20317 ( GABRB3 ) under the heterozygote model; A1298C ( MTHFR ) under allelic, dominant, heterozygote, and recessive models; C677T ( MTHFR ) under homozygote and recessive models; rs736707 ( RELN ) under allelic, dominant, and homozygote models; 5-HTTLPR ( SLC6A4 ) under allelic and recessive models; rs11568820 ( VDR ) under the dominant model; and rs731236 ( VDR ) under the heterozygote model, with statistically significant ( P  < 0.05) excess of positive studies (Table 4 ).

We categorized the strength of the evidence of 20 SNPs for ASD into five levels. According to the criteria for the level of evidence, for rs2710102 ( CNTNAP2 ), the P -value based on the random effects model was significant at P  < 0.05 under allelic, homozygote, and recessive models. Between-study heterogeneity was not significant ( P  > 0.10, I²  < 50.0%), the 95% PI did not exclude the null value, and there was no excess significance bias ( P  > 0.05) under the five genetic models. For rs7794745 ( CNTNAP2 ), the P -value based on the random effects model was significant at P  < 0.05 under dominant and heterozygote models. For C677T ( MTHFR ), there was a total of 2147 ASD cases, which was > 1000, and the P -value based on the random effects model was significant at P  < 10 –3 under allelic, dominant, and heterozygote models. Moreover, it was significant at P  < 0.05 under the homozygote model. Between-study heterogeneity was large ( I²  > 50.0%) under the five genetic models, the 95% PI did not exclude the null value under the five genetic models, and there was no excess significance bias ( P  > 0.05) under allelic, dominant, and heterozygote models. For rs731236 ( VDR ), there was a total of 1088 ASD cases, which was >1000, the P -value based on the random effects model was significant at P  < 10 –3 under allelic and homozygote models, and the P -value was significant at P  < 0.05 under dominant and recessive models. Between-study heterogeneity was not significant ( P  > 0.10, I²  < 50.0%), the 95% PI excluded the null value, and there was no small-study effect ( P  > 0.10) and excess significance bias ( P  > 0.05) under the five genetic models (Table 4 ). Thus, the rs2710102 ( CNTNAP2 ) was graded as weak evidence (class IV) under allelic, homozygote, and recessive models; rs7794745 ( CNTNAP2 ) was graded as weak evidence (class IV) under dominant and heterozygote models; the C677T ( MTHFR ) was graded as suggestive evidence (class III) under allelic, dominant, and heterozygote models; C677T ( MTHFR ) was graded as weak evidence (class IV) under the homozygote model; VDR (rs731236) was graded as suggestive evidence (class III) under allelic and homozygote models; and VDR (rs731236) was graded as weak evidence (class IV) under dominant and recessive models.

This UR summarizes evidence on the genetic basis of ASD. Our study design provides a robust and significant synthesis of published evidence and increases the conclusive power with more precise estimates. Overall, 12 significant SNPs of CNTNAP2 , MTHFR , OXTR , SLC25A12 , and VDR were identified from 41 SNPs of nine candidate genes in 28 meta-analyses. Of those, associations with suggestive evidence (class III) were the C677T polymorphism of MTHFR (under allelic, dominant, and heterozygote models) and rs731236 polymorphism of VDR (under allelic and homozygote models). Associations with weak evidence (class IV) were the rs2710102 polymorphism of CNTNAP2 (under allelic, homozygote, and recessive models), rs7794745 polymorphism of CNTNAP2 (under dominant and heterozygote models), C677T polymorphism of MTHFR (under homozygote model), and rs731236 polymorphism of VDR (under dominant and recessive models).

ASD remains a ‘disease of theories’, as multiple genes and environmental risk factors are probably involved in its pathogenesis. However, to date, the etiology and pathological mechanism of ASD are still unknown [ 57 ]. The genetic architecture of ASD is complex. Moreover, most research in this field has focused on candidate genes, primarily those with a plausible role in the known underlying pathophysiology, including mitochondrial dysfunction, abnormal neurodevelopment, and dysfunction of synapse formation and stability during neurodevelopment [ 58 , 59 ].

CNTNAP2 is a member of neurexin superfamily and is a synaptic protein [ 60 ]. It plays a major role in neural development, crucial for neural circuit assembly [ 61 ]. CNTNAP2 mutations may be linked to the abnormal behavior of ASD by altering synaptic neurotransmission, functional connectivity, and neuronal network activity [ 61 , 62 ]. The rs2710102 and rs7794745 are two common non-coding variants in CNTNAP2 , with four and three meta-analyses reporting the associations with ASD, respectively. The results of the meta-analysis by Uddin et al. were inconsistent with the other authors’ [ 44 ]. We further re-analyzed and categorized the strengths of evidence. Both the rs2710102 and rs7794745 polymorphisms of CNTNAP2 were associated with decreased risk of ASD. The rs2710102 was graded as having a weak association with ASD under allelic, homozygote, and recessive models. The rs7794745 was graded as having a weak association with ASD under dominant and heterozygote models. Therefore, it is likely that the rs2710102 and rs7794745 polymorphisms of CNTNAP2 influence the risk of ASD.

MTHFR is one of the most frequently-researched genes in ASD, with four and eight meta-analyses for A1298C [ 29 , 31 , 32 , 33 ] and C667T [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] polymorphisms, respectively. The A1298C and C667T polymorphisms of MTHFR are associated with reduced enzymatic activity, which affects folate metabolism, and, consequently, fetal brain development [ 29 , 32 , 33 ]. Dysfunction of the brain is indicated in ASD etiology; thus, MTHFR has been the focal point of investigation in this disorder. The meta-analysis by Li et al. was selected because it was the most recent among the examined meta-analyses [ 34 ]. The genotype distributions of the A1298C and C667T polymorphisms of MTHFR in the control group were not found in the HWE, which may be due to selection bias, population stratification, and genotyping errors within the original studies. We found no significant association between the A1298C polymorphism of MTHFR and ASD risk in the five genetic models, which was consistent with the four meta-analyses, indicating that the A1298C polymorphism of MTHFR may not be a risk SNP of ASD. We found that the C667T polymorphism of MTHFR was associated with an increased risk of ASD, graded as having suggestive association under allelic, dominant, and heterozygote models and weak association under the homozygote model. Thus, the C667T polymorphism of MTHFR may confer ASD risk.

OXTR, a neuropeptide gene, is also one of the most frequently-studied genes associated with ASD [ 45 ]. Oxytocin plays an important role in a range of human behaviors, including affiliative behavior to social bonding, and is differentially expressed in the blood of individuals with autism compared to that of non-autistic individuals [ 45 , 63 ]. Three meta-analyses investigated 19 SNPs and ASD risk. Of these, only rs2254298 and rs53576 were analyzed in two meta-analyses [ 45 , 46 ], and the remaining SNPs were unique in one meta-analysis. Three SNPs (rs2268491, rs237887, and rs7632287) were significantly associated with ASD risk [ 45 , 46 ]; however, we failed to determine the credibility of the evidence because of the lack of original data.

RELN encodes a large secreted extracellular matrix protein considered to be involved in neuronal migration, brain structure construction, synapse formation, and stability during neurodevelopment [ 59 ]. Fatemi et al. found decreased levels of reelin mRNA and protein and increased levels of reelin receptors in the brain and plasma of individuals with autism [ 64 ]. Dysfunction of the reelin signaling pathway has been found in ASD, schizophrenia, epilepsy, bipolar disorder, mental retardation, depression, Alzheimer’s disease, and lissencephaly [ 59 , 65 ]. Genetic association studies have been conducted to investigate the associations between SNPs within RELN and ASD with conflicting results. None of the three meta-analyses found significant associations [ 48 , 49 , 50 ]. The meta-analysis by Hernández-García et al. was retained for further analysis of the original studies after comparing publication years and sample sizes of the three meta-analyses [ 50 ]. Hernández-García et al. did not find a significant association between RELN and ASD risk [ 50 ]. In our analysis, because there was no substantial statistical heterogeneity under the five genetic models (all P  > 0.10, I 2  ≤ 50%), a fixed model was applied to pool the effect size. We found that the rs607755 of RELN was associated with ASD risk in allelic, dominant, heterozygote, and homozygote models. This inconsistent result was caused by different pooling methods, indicating that it is necessary to perform an UR to provide a robust synthesis of published evidence and evaluate the importance of genetic factors related to ASD. Our UR results showed that the rs607755 of RELN was not significant when we categorized the strength of the evidence. Thus, it may not be a risk factor for ASD.

SLC25A12 encodes the mitochondrial aspartate/glutamate carrier of the brain, a calcium-binding solute carrier located in the inner mitochondrial membrane that is expressed principally in the heart, brain, and skeletal muscle [ 66 , 67 ]. Rossignol et al. found that individuals with ASD had a significantly higher prevalence of mitochondrial diseases than that of controls, indicating the involvement of mitochondrial dysfunction in ASD [ 58 ]. Thus, an increasing number of genetic studies on ASD have focused on SLC25A12 . However, the results on the association between SNPs of SLC25A12 and ASD risk are inconsistent. Two meta-analyses were performed by Aoki et al. [ 53 ] and Liu et al. [ 54 ], and despite differences in the number of studies between the two meta-analyses, both found a higher risk of ASD in individuals with the mutant allele of rs2056202 or rs2292813. However, we failed to determine the credibility of the evidence because of a lack of original data.

Vitamin D plays a significant role in brain homeostasis, neurodevelopment, and immunological modulation, and its deficiency has been reported in children with ASD [ 68 ]. Hence, changes in the genes involved in the transport or binding of vitamin D may be associated with ASD risk. Notably, vitamin D exerts its effects on genes via the VDR gene, to which changes may be an underlying risk factor for ASD. Sun et al. [ 55 ] and Yang et al. [ 56 ] performed meta-analyses to pool the effect size of inconsistent conclusions from original studies on the associations between SNPs in VDR and ASD risks. We further re-analyzed and categorized the strengths of evidence. The rs731236 polymorphism of VDR was associated with an increased risk of ASD, graded as having a suggestive association under allelic and homozygote models and a weak association under dominant and recessive models without small-study effects, excess significance bias, and large heterogeneity. It is likely that the VDR rs731236 polymorphism influences the risk of ASD.

Our study has some limitations. First, associations between several SNPs and ASD risks under five genetic models or in different populations were not fully assessed in our UR, partly due to insufficient original data. Second, our UR is limited by significant heterogeneity that may be caused by population stratification, study design, and differences in the pattern of linkage disequilibrium structure. Finally, ASD is a complex disorder with different causative factors (multiple genetic and environmental factors). We did not investigate the involvement of environmental factors in ASD. Despite these limitations above, our UR includes its prospective registration with PROSPERO, an extensive search strategy, clear criteria of inclusion and exclusion, duplicated processing by two authors, accurate quality assessment, systematic assessment and critical comparison of meta-analyses, and consistent standards for re-analysis of original data.

In conclusion, our UR summarizes evidence on the genetics of ASD and provides a broad and detailed overview of risk genes for ASD. The rs2710102 and rs7794745 polymorphisms of CNTNAP2 , C677T polymorphism of MTHFR , and rs731236 polymorphism of VDR may confer ASD risk. This study will aid clinicians in decision-making through the use of evidence-based information on the most salient candidate genes relevant to ASD and recommendations for future treatment, prevention, and research.

Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383:896–910.

Article   PubMed   Google Scholar  

WHO Questions and answers about autism spectrum disorders (ASD). 2021; http://www.who.int/features/qa/85/en/ . Accessed 5 July 2021.

Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG. The epidemiology and global burden of autism spectrum disorders. Psychological Med. 2015;45:601–13.

Article   CAS   Google Scholar  

Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012;14:281–92.

Article   PubMed   PubMed Central   Google Scholar  

Kim JY, Son MJ, Son CY, Radua J, Eisenhut M, Gressier F, et al. Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence. lancet Psychiatry. 2019;6:590–600.

Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, et al. Autism spectrum disorder. Nat Rev Dis Prim. 2020;6:5.

Ronald A, Hoekstra RA. Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet Part B, Neuropsychiatr Genet: Off Publ Int Soc Psychiatr Genet. 2011;156b:255–74.

Article   Google Scholar  

Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA. 2014;311:1770–7.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, et al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. 2011;147:235–46.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Qiu S, Li Y, Bai Y, Shi J, Cui H, Gu Y, et al. SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: a possible cue for recognition to autism spectrum disorder in infant age. Autism Res. 2019;12:375–83.

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51:431–44.

Ioannidis JP. Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses. CMAJ: Can Med Assoc J = J de l’Assoc Med Canadienne. 2009;181:488–93.

van der Burg NC, Al Hadithy AFY, van Harten PN, van Os J, Bakker PR. The genetics of drug-related movement disorders, an umbrella review of meta-analyses. Mol Psychiatry. 2020;25:2237–50.

Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, Grimshaw J, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol. 2009;62:1013–20.

Giannakou K, Evangelou E, Papatheodorou SI. Genetic and non-genetic risk factors for pre-eclampsia: umbrella review of systematic reviews and meta-analyses of observational studies. Ultrasound Obstet Gynecol. 2018;51:720–30.

Article   CAS   PubMed   Google Scholar  

Yang T, Li X, Montazeri Z, Little J, Farrington SM, Ioannidis JPA, et al. Gene-environment interactions and colorectal cancer risk: an umbrella review of systematic reviews and meta-analyses of observational studies. Int J Cancer. 2019;145:2315–29.

Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–6.

Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J Roy Soc Statistical Soc A (Stat Soc). 2009;172:137–59.

Higgins JP. Commentary: Heterogeneity in meta-analysis should be expected and appropriately quantified. Int J Epidemiol. 2008;37:1158–60.

Cochran WGJB. Combination Estimates Differ Exp. 1954;10:101–29.

Google Scholar  

Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

Ioannidis JP, Patsopoulos NA, Evangelou E. Uncertainty in heterogeneity estimates in meta-analyses. BMJ (Clin Res Ed). 2007;335:914–6.

Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ (Clin Res Ed). 2011;343:d4002.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Clin Focus. 1997;315:629–34.

CAS   Google Scholar  

Ioannidis JPA. Clarifications on the application and interpretation of the test for excess significance and its extensions. J Math Psychol. 2013;57:184–7.

Belbasis L, Köhler CA, Stefanis N, Stubbs B, van Os J, Vieta E, et al. Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta-analyses. Acta Psychiatr Scand. 2018;137:88–97.

Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JP. Environmental risk factors and Parkinson’s disease: an umbrella review of meta-analyses. Parkinsonism Relat Disord. 2016;23:1–9.

Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol. 2015;14:263–73.

Pu D, Shen Y, Wu J. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res. 2013;6:384–92.

Rai V. Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility. Metab Brain Dis. 2016;31:727–35.

Sadeghiyeh T, Dastgheib SA, Mirzaee-Khoramabadi K, Morovati-Sharifabad M, Akbarian-Bafghi MJ, Poursharif Z, et al. Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: a systematic review and meta-analysis. Asian J Psychiatry. 2019;46:54–61.

Razi B, Imani D, Hassanzadeh Makoui M, Rezaei R, Aslani S. Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: systematic review and meta-analysis. Res Autism Spectrum Disorders. 2020;70:101473.

Li Y, Qiu S, Shi J, Guo Y, Li Z, Cheng Y, et al. Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis. BMC Pediatrics. 2020;20:449.

Li CX, Liu YG, Che YP, Ou JL, Ruan WC, Yu YL, et al. Association between MTHFR C677T polymorphism and susceptibility to autism spectrum disorders: a meta-analysis in Chinese Han population. Front Pediatrics. 2021;9:598805.

Wang S, Wu J. Association between MTHFR gene C677T polymorphism and risk of autism spectrum disorder in children: a Meta-analysis. Chin J Obstet Gynecol Pediatr. 2021;17:198–206.

Zhang Y, Gai C, Yang L, Ma H, Zhang J, Sun H, et al. Meta-analysis of the relationship between MTHFR C677T gene polymorphism and susceptibility to autism spectrum disorders. Tianjin Med J. 2021;49:212–8.

Huang CH, Santangelo SL. Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis. Am J Med Genet B: Neuropsychiatr Genet. 2008;147b:903–13.

Mo S, Qi X, Shao S, Sun Z, Song R. An integrated meta-analysis of the association between 5-HTTLPR and autism spectrum disorder. Acta Med Univ Sci Technol Huazhong. 2013;42:181–6.

Yang PY, Menga YJ, Li T, Huang Y. Associations of endocrine stress-related gene polymorphisms with risk of autism spectrum disorders: evidence from an integrated meta-analysis. Autism Res. 2017;10:1722–36.

Wang H, Yin F, Gao J, Fan X. Association between 5-HTTLPR polymorphism and the risk of autism: a meta-analysis based on case-control studies. Front psychiatry. 2019;10:51.

CAS   PubMed   PubMed Central   Google Scholar  

Werling AM, Bobrowski E, Taurines R, Gundelfinger R, Romanos M, Grünblatt E, et al. CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches. J Neural Transm. 2016;123:353–63. (Vienna, Austria: 1996)

Zhang T, Zhang J, Wang Z, Jia M, Lu T, Wang H, et al. Association between CNTNAP2 polymorphisms and autism: a family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium. Autism Res. 2019;12:553–61.

Wang Y, Liu Y, Xia Z, Yu H, Gai Z. Association of the contactin-association protein-like 2 gene rs2710102 polymorphism and autism spectrum disorders: a meta-analysis. Clin Focus. 2019;34:1010–4.

Uddin MS, Azima A, Aziz MA, Aka TD, Jafrin S, Millat MS, et al. CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis. Hum Cell. 2021;34:1410–23.

LoParo D, Waldman ID. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry. 2015;20:640–6.

Kranz TM, Kopp M, Waltes R, Sachse M, Duketis E, Jarczok TA, et al. Meta-analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder. Autism Res. 2016;9:1036–45.

Zhou J. Association between the single nucleotide polymorphism (SNP) of oxytocin receptor (OXTR) gene and Autism Spectrum Disorders (ASD): a meta-analysis. Jining Medical University. 2020.

Wang Z, Hong Y, Zou L, Zhong R, Zhu B, Shen N, et al. Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis. Am J Med Genet Part B: Neuropsychiatr Genet. 2014;165b:192–200.

Chen N, Bao Y, Xue Y, Sun Y, Hu D, Meng S, et al. Meta-analyses of RELN variants in neuropsychiatric disorders. Behav Brain Res. 2017;332:110–9.

Hernández-García I, Chamorro AJ, de la Vega HGT, Carbonell C, Marcos M, Mirón-Canelo JA. Association of allelic variants of the reelin gene with autistic spectrum disorder: A systematic review and meta-analysis of candidate gene association studies. Int J Environ Res Public Health. 2020;17:1–16.

Mahdavi M, Kheirollahi M, Riahi R, Khorvash F, Khorrami M, Mirsafaie M. Meta-analysis of the association between GABA receptor polymorphisms and autism spectrum disorder (ASD). J Mol Neurosci. 2018;65:1–9.

Noroozi R, Taheri M, Ghafouri-Fard S, Bidel Z, Omrani MD, Moghaddam AS, et al. Meta-analysis of GABRB3 gene polymorphisms and susceptibility to autism spectrum disorder. J Mol Neurosci. 2018;65:432–7.

Aoki Y, Cortese S. Mitochondrial aspartate/glutamate carrier SLC25A12 and autism spectrum disorder: a meta-analysis. Mol Neurobiol. 2016;53:1579–88.

Liu J, Yang A, Zhang Q, Yang G, Yang W, Lei H, et al. Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis. Am J Med Genet Part B: Neuropsychiatr Genet. 2015;168b:236–46.

Sun J. Association between vitamin D receptor gene polymorphism and susceptibility to autism spectrum disorders: a meta-analysis. Jining Medical University. 2020.

Yang H, Wu X. The correlation between vitamin D receptor (VDR) gene polymorphisms and autism: a meta-analysis. J Mol Neurosci. 2020;70:260–8.

Kojic M, Gawda T, Gaik M, Begg A, Salerno-Kochan A, Kurniawan ND, et al. Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype. Nat Commun. 2021;12:2678.

Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol psychiatry. 2012;17:290–314.

Jossin Y. Reelin functions, mechanisms of action and signaling pathways during brain development and maturation. Biomolecules. 2020;10:964.

Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, et al. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet. 2008;82:160–4.

Lazaro MT, Taxidis J, Shuman T, Bachmutsky I, Ikrar T, Santos R, et al. Reduced prefrontal synaptic connectivity and disturbed oscillatory population dynamics in the CNTNAP2 model of autism. Cell Rep. 2019;27:2567–2578.e2566.

Toma C, Pierce KD, Shaw AD, Heath A, Mitchell PB, Schofield PR, et al. Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders. PLoS Genet. 2018;14:e1007535.

Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, et al. Plasma oxytocin levels in autistic children. Biol psychiatry. 1998;43:270–7.

Fatemi SH. Reelin glycoprotein: structure, biology and roles in health and disease. Mol psychiatry. 2005;10:251–7.

Fatemi SH. Reelin glycoprotein in autism and schizophrenia. Int Rev Neurobiol. 2005;71:179–87.

Silverman JM, Buxbaum JD, Ramoz N, Schmeidler J, Reichenberg A, Hollander E, et al. Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism. Am J Med Genet B: Neuropsychiatr Genet. 2008;147:408–10.

Anitha A, Nakamura K, Thanseem I, Yamada K, Iwayama Y, Toyota T, et al. Brain region-specific altered expression and association of mitochondria-related genes in autism. Mol Autism. 2012;3:12.

Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjørklund G, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutritional Neurosci. 2016;19:346–51.

Download references

Acknowledgements

This study was funded by the Science and Technology Department of Jilin Province (grant number: 20200601010JC).

Author information

Authors and affiliations.

Department of Biobank, China-Japan Union Hospital, Jilin University, Changchun, 130033, Jilin, China

Shuang Qiu & Xianling Cong

China-Japan Union Hospital, Jilin University, Changchun, 130033, Jilin, China

Yingjia Qiu

Department of Epidemiology, School of Public Health, Beihua University, Jilin, 132013, Jilin, China

You can also search for this author in PubMed   Google Scholar

Contributions

Study design: S.Q. and X.C. Data collection, analysis, and interpretation: S.Q., Y.Q., and Y.L. Drafting of the manuscript: S.Q. Critical revision of the manuscript: X.C. Approval of the final version for publication: all co-authors.

Corresponding author

Correspondence to Xianling Cong .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Qiu, S., Qiu, Y., Li, Y. et al. Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses. Transl Psychiatry 12 , 249 (2022). https://doi.org/10.1038/s41398-022-02009-6

Download citation

Received : 08 January 2022

Revised : 22 May 2022

Accepted : 27 May 2022

Published : 15 June 2022

DOI : https://doi.org/10.1038/s41398-022-02009-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Support vector machine prediction of individual autism diagnostic observation schedule (ados) scores based on neural responses during live eye-to-eye contact.

• J. Adam Noah

Scientific Reports (2024)

Parental Perspectives on Early Life Screening and Genetic Testing for ASD: A Systematic Review

• Katerina Dounavi
• Meral Koldas

Journal of Autism and Developmental Disorders (2024)

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure

• Matthew R. Bruce
• Amalie C. M. Couch
• Judy Van de Water

Molecular Psychiatry (2023)

Calciopathies and Neuropsychiatric Disorders: Physiological and Genetic Aspects

• N. A. Dyuzhikova
• M. B. Pavlova

Neuroscience and Behavioral Physiology (2023)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

What Causes Autism? Understanding the Latest Research

FEATURED POSTS

Hanna Rue, Ph.D., BCBA-D, chief clinical officer

What does science say about what causes autism? The latest research indicates that a combination of genetic and environmental factors likely causes it.

There’s no simple answer, and scientists are still trying to develop better ones. “What caused my child’s autism? Was I to blame?” As David G. Amaral, Ph.D., a psychiatry and behavioral sciences professor at the University of California Davis wrote in 2017 in the journal Cerebrum , “Autism research has made tremendous progress over the last 20 years, but yet we still can’t provide definitive answers to most of these questions.”

What We Know for Sure

What we know for sure is that autism is a complex condition. It’s not caused by one single factor. The exact cause is still not fully understood, making it a subject of ongoing research.

Much of that research involves two main categories:

• Genetic factors: Scientists have found that certain gene changes, unusual gene combinations, and other genetic conditions can make a person more likely to have autism.
• Environmental factors: Since genetic factors don’t always lead to autism, that suggests that environmental factors could play a role. That could include factors, such as prenatal exposure to certain drugs or chemicals, complications during birth, or advanced parental age at the time of conception.

What Myths about Autism Science Has Debunked

Science has debunked several myths about autism, most notably the claim that vaccines cause autism. Large-scale studies have proven this theory to be false. Other debunked myths include the idea that autism is caused by parenting style or that it’s a mental health disorder . Autism is actually a neurological disorder resulting from differences in brain development.

It’s also worth noting that the prevalence of autism is rising, but this doesn’t necessarily mean more people are becoming autistic. An article in Scientific American explains that the bulk of the increase in autism rates stems from growing awareness of autism and better diagnostic methods.

Where Research Is Headed

The latest research in autism focuses on understanding the genetic and neurological aspects of the condition. Studies are further examining the perceptions of counselors in treating children with autism , which could help improve therapeutic approaches.

Other research is debunking more myths about vaccination risks related to autism . Still other researchers are looking into the intersection of autism in adulthood and the LGBTQ+ community . And some new research is looking into how certain proteins associated with autism interact with other molecules , shaping synaptic plasticity.

Our Understanding of Autism Is Evolving

Yet the most basic question — “What caused my child’s autism?” — may have no simple answer. Little by little, our understanding of what causes autism is evolving.

It’s becoming clearer that the causes of autism are multifaceted. While we might not have all the answers now, we are continuing to unravel the complexities of autism.

• April 16, 2024 | X-Ray Eyes Reveal Hidden Winds of Sun-Like Stars for the First Time
• April 16, 2024 | Quantum Leap: Rice Physicists Unlock Flash-Like Memory for Future Qubits
• April 16, 2024 | Revolutionizing 3D: New Holographic Technique Breaks Computational Barriers
• April 16, 2024 | This Common Household Habit Could Be Increasing Your Risk of ALS
• April 16, 2024 | “Neutronic Molecules” – Neutrons Meet Quantum Dots in Groundbreaking MIT Discovery

Groundbreaking Study Reveals Autism’s Genetic Triggers and Therapeutic Hope

By Juntendo University Research Promotion Center April 13, 2024

A groundbreaking study involving researchers from Japanese institutions revealed the genetic and epigenetic mechanisms behind autism spectrum disorder, using a KMT2C haploinsufficiency mouse model. Credit: SciTechDaily.com

Japanese scientists uncover the genetic basis of autism through a study on KMT2C haploinsufficiency in mice, revealing the therapeutic promise of vafidemstat in treating ASD-related symptoms.

Autism spectrum disorder (ASD) encompasses neurodevelopmental conditions where patients display repetitive behavior and impaired sociality. Genetic factors have been shown to influence the development of ASD. Additionally, recent studies have shown that the genes involved in chromatin modification and gene transcription are involved in the pathogenesis of ASD.

Among the many genes implicated in this process, the gene KMT2C ( lysine methyltransferase 2c ), which codes for a catalytic unit of H3K4 (histone H3 lysine 4) methyltransferase complex, has been identified to be associated with the development of autism and other neurodevelopmental disorders. Previous studies have shown that haploinsufficiency (a condition where, of the two copies of the gene, only one remains functional) of KMT2C is a risk factor for ASD and other neurodevelopmental disorders. However, the molecular mechanism through which the loss-of-function mutation in KMT2C leads to these conditions remains unclear.

Pioneering Research in Japan

To address this knowledge gap, researchers from Juntendo University, RIKEN, and the University of Tokyo in Japan aimed to provide answers to these questions in a benchmark study published in the journal Molecular Psychiatry on March 26, 2024. The research team included Professor Tadafumi Kato from the Department of Psychiatry and Behavioral Science at Juntendo University Graduate School of Medicine, Dr. Takumi Nakamura and Dr. Atsushi Takata from the RIKEN Center for Brain Science, and Professor Takashi Tsuboi from Graduate School of Arts and Sciences, The University of Tokyo.

Genes involved in chromatin modification and gene transcription are associated with the progression of neurodevelopmental disorders. Researchers from Japan have developed a new mouse model to study the molecular mechanism behind the ability of KMT2C to cause autism spectrum disorder. They also showed that vafidemstat has a rescuing effect by normalizing disrupted gene expression. Credit: Tadafumi Kato from Juntendo University, Japan

To get to the bottom of KMT2C ’s role in ASD pathogenesis, the team developed and analyzed genetically engineered strain mice ( Kmt2c +/fs ) having a frameshift mutation that models the KMT2C haploinsufficiency. They then performed various behavioral analyses, in which they observed that the mutant mice exhibited lower sociality, inflexibility, auditory hypersensitivity, and cognitive impairments, which are all ASD-related symptoms.

Genetic and Epigenetic Insights

Next, they performed transcriptomic and epigenetic profiling to understand the basis of the molecular changes observed in the mutant mice. What they discovered was remarkable: the genes associated with increased ASD risk showed higher expression in these mutant mice. Dr. Takata exclaims, “This was somewhat unexpected. KMT2C mediates H3K4 methylation, which is thought to activate gene expression, and thereby KMT2C haploinsufficiency was expected to cause reduced expression of target genes.”

To gain mechanistic insights into their finding, the researchers carried out chromatin immunoprecipitation, a technique to determine the location on the DNA where the protein interacts with it. They found an overlap between KMT2C and the differentially expressed genes exhibiting reduced expression, suggesting that KMT2C haploinsufficiency leads to ASD-related transcriptomic changes through an indirect effect on gene expression.

Further, to identify the cell types that contribute more to the pathological changes seen in the mutant mice, the researchers performed single-cell RNA sequencing of newborn mice brains. They observed that the altered genes associated with ASD risk were predominant in undifferentiated radial glial cells. However, a gross change in the cell composition was not observed, implying that the transcriptomic dysregulation does not severely impact cell fate.

Therapeutic Potential of Vafidemstat

Finally, the researchers tested the effects of vafidemstat, a brain penetrant inhibitor of LSD1 (lysine-specific histone demethylase 1A), that could ameliorate histone methylation abnormalities. They found that vafidemstat improved the social deficits in the mutant mice and had an exceptional rescuing effect by changing the expression levels of the differentially expressed genes to their normal expression level. This finding showed that vafidemstat is a valid drug for mutant mice and can potentially help restore the normal transcriptomic state.

What sets this discovery apart is that it challenges the commonly held belief that ASD disability may not be cured and demonstrates the efficacy of vafidemstat in improving ASD-like phenotypes. The results open doors to future research to strengthen the foundation for the pharmacologic treatment of ASD and other neurodevelopmental disorders. Prof. Kato concludes, “Our research shows that drugs similar to vafidemstat may be generalizable to multiple categories of psychiatric disorders.”

Reference: “Transcriptomic dysregulation and autistic-like behaviors in Kmt2c haploinsufficient mice rescued by an LSD1 inhibitor” by Takumi Nakamura, Toru Yoshihara, Chiharu Tanegashima, Mitsutaka Kadota, Yuki Kobayashi, Kurara Honda, Mizuho Ishiwata, Junko Ueda, Tomonori Hara, Moe Nakanishi, Toru Takumi, Shigeyoshi Itohara, Shigehiro Kuraku, Masahide Asano, Takaoki Kasahara, Kazuo Nakajima, Takashi Tsuboi, Atsushi Takata and Tadafumi Kato, 26 March 2024, Molecular Psychiatry . DOI: 10.1038/s41380-024-02479-8

More on SciTechDaily

Galactic Surprise: James Webb Space Telescope Unveils Hidden Companion Galaxy

New Technology Gives AI Human-Like Eyes

Astronomers Discover a Supervoid 1.8 Billion Light Years Across

Harvard Scientists Reveal How Squid and Octopus Get Their Big Brains

Strange Galactic Signal Coming From the Center of the Galaxy Has Potential New Explanation

Counting Conundrum – Nerve Cells Can Detect Small Numbers of Things Better Than Large Numbers of Things

A Breakthrough in Genome Editing: How NICER Outperforms CRISPR/Cas9

Coronal Mass Ejections Accelerate and Concentrate Nanodust Particles

1 comment on "groundbreaking study reveals autism’s genetic triggers and therapeutic hope".

wonderful this article

Congratulations ¡¡

Leave a comment Cancel reply

Email address is optional. If provided, your email will not be published or shared.

Save my name, email, and website in this browser for the next time I comment.

Your Internet Explorer 11 browser is not supported by this site. Please upgrade to a recent browser for the best experience.

The causes of autism

The causes of autism are still being looked into. Many experts believe that there isn't one specific 'cause', and that there are genetic factors. We are always looking to understand more about autism, and welcome any research in this area.

Possible causes

Evidence suggests that autism may be genetic. Scientists have been attempting to identify which genes might be implicated in autism for some years. Autism is likely to have multiple genes responsible rather than a single gene. However, it is not caused by emotional deprivation or the way a person has been brought up.

There is no link between autism and vaccines. Much research has been devoted to this issue over the years and the results have comprehensively shown there is no link. Find out more on the NHS website.

Is there a 'cure' for autism?

There is no known 'cure' for autism. We also believe that autism does not need a 'cure' and should be seen as a difference, not a disadvantage.  We also warn people about fake cures and potentially harmful interventions here . 

This does not mean that autistic people do not face challenges, but with the right support in place, they are more than capable of living fulfilling and happy lives.  Because autism is a 'spectrum' condition it affects different people in different ways. It is therefore very difficult to generalise about how an autistic person will develop over time. Each person is different, and an intervention or coping strategy which works well with one person may not be appropriate or effective with another. The characteristics of autism can present themselves in a wide variety of combinations. Two people with the same diagnosis can have a very different profile of needs and skills.

Valuing neurodiversity

There is a growing movement among autistic adults who don't think in terms of 'curing' a disorder but instead of celebrating diversity. This is not to suggest that autistic people or those with other diagnoses do not find life challenging, but that they see it as a different way of communicating, thinking, and interacting.  

What autistic people have to say

Through our Stories from the Spectrum series, we’ve spoken to several autistic people, who have shared their thoughts on this topic, what being autistic is like for them, and some of the positive aspects of being autistic.

"I just seem to see and think about people and the world in a different way. It's part of who I am." John Clark

John Clark , autistic filmmaker, told us: "I just seem to see and think about people and the world in a different way. For instance, I am both confused and fascinated by idioms. It’s part of who I am. I used to be very self-conscious about people liking and accepting me, but now, I just think, “take me or leave me”. We’re all different. Some people seem to find ‘live and let live’ a difficult mantra to grasp though."

Patrick Samuel , autistic artist and musician, said: "My autism makes it easy for me to do things a lot of non-autistic people may struggle with. I work intensely when I’m painting, writing, composing or doing anything creative. I think being autistic also contributes to my aptitude in problem solving and pattern recognition, which can help me research a highly specialised subject and give talks on it."

Harri Wilson , autistic junior doctor, said: "I always notice lots of details other people miss and this can be really important in making the right diagnosis at work, or picking up that a patient is deteriorating. I also have an excellent memory, which really helps in my job. I can’t really recognise or remember faces though – this can make things tricky when many of my colleagues wear the same uniforms!"  

Recommended reading and resources

Organisations you may find helpful, autism rights group highland.

a website with a number of articles and recordings.

Autistic Rights Together

National autistic people's organisation, articles and blogs.

• Is autism really a disorder? - an article by Luke Beardon
• Identity-First Autistic - a collection of blogs and articles on identity-first language
• Institute for the Study of the Neurologically Typical - a humorous blog post on treatment for neurotypicals (people who are not on the autism spectrum), born of outrage at attitudes to autistic people
• Square talk: the social model

Autism research

Autism research centre.

University of Cambridge

Autistica's research

So-called cures and dodgy interventions

Here you can find information and warnings about so-called 'cures' for autism, harmful or unhelpful therapies, and how to spot them.

Stories from the Spectrum

Autistic people and their friends and families share their experiences of life on the spectrum. There are funny stories, thought-provoking stories, moving and challenging stories.

The Spectrum magazine

Explore one of the UK's largest collections of autistic art, poetry, and prose. The Spectrum magazine is created by and for autistic people, and is available both online and in print.

Was this page helpful?

You are not alone

Join the community.

Our online community is a place for autistic people and their families to meet like-minded people and share their experiences.

Cookies on this site

Our site uses cookies for key functions and to give you the best experience. Use cookie settings to control which cookies are allowed or click on Allow Optional Cookies to allow all cookies. For more detailed information please see our cookie policy .

Please wait while we check your current settings

Study identifies new metric for diagnosing autism

Autism spectrum disorder has yet to be linked to a single cause, due to the wide range of its symptoms and severity. However, a study by University of Virginia researchers suggests a promising new approach to finding answers, one that could lead to advances in the study of other neurological conditions.

Current approaches to autism research involve observing and understanding the disorder through the study of its behavioral consequences, using techniques like functional magnetic resonance imaging that map the brain's responses to input and activity, but little work has been done to understand what's causing those responses.

However, researchers with UVA's College and Graduate School of Arts & Sciences have been able to better understand the physiological differences between the brain structures of autistic and non-autistic individuals through the use of Diffusion MRI, a technique that measures molecular diffusion in biological tissue, to observe how water moves throughout the brain and interacts with cellular membranes. The approach has helped the UVA team develop mathematical models of brain microstructures that have helped identify structural differences in the brains of those with autism and those without.

"It hasn't been well understood what those differences might be," said Benjamin Newman, a postdoctoral researcher with UVA's Department of Psychology, recent graduate of UVA School of Medicine's neuroscience graduate program and lead author of a paper published this month in PLOS: One . "This new approach looks at the neuronal differences contributing to the etiology of autism spectrum disorder."

Building on the work of Alan Hodgkin and Andrew Huxley, who won the 1963 Nobel Prize in Medicine for describing the electrochemical conductivity characteristics of neurons, Newman and his co-authors applied those concepts to understand how that conductivity differs in those with autism and those without, using the latest neuroimaging data and computational methodologies. The result is a first-of-its-kind approach to calculating the conductivity of neural axons and their capacity to carry information through the brain. The study also offers evidence that those microstructural differences are directly related to participants' scores on the Social Communication Questionnaire, a common clinical tool for diagnosing autism.

"What we're seeing is that there's a difference in the diameter of the microstructural components in the brains of autistic people that can cause them to conduct electricity slower," Newman said. "It's the structure that constrains how the function of the brain works."

One of Newman's co-authors, John Darrell Van Horn, a professor of psychology and data science at UVA, said, that so often we try to understand autism through a collection of behavioral patterns which might be unusual or seem different.

"But understanding those behaviors can be a bit subjective, depending on who's doing the observing," Van Horn said. "We need greater fidelity in terms of the physiological metrics that we have so that we can better understand where those behaviors coming from. This is the first time this kind of metric has been applied in a clinical population, and it sheds some interesting light on the origins of ASD."

Van Horn said there's been a lot of work done with functional magnetic resonance imaging, looking at blood oxygen related signal changes in autistic individuals, but this research, he said "Goes a little bit deeper."

"It's asking not if there's a particular cognitive functional activation difference; it's asking how the brain actually conducts information around itself through these dynamic networks," Van Horn said. "And I think that we've been successful showing that there's something that's uniquely different about autistic-spectrum-disorder-diagnosed individuals relative to otherwise typically developing control subjects."

Newman and Van Horn, along with co-authors Jason Druzgal and Kevin Pelphrey from the UVA School of Medicine, are affiliated with the National Institute of Health's Autism Center of Excellence (ACE), an initiative that supports large-scale multidisciplinary and multi-institutional studies on ASD with the aim of determining the disorder's causes and potential treatments.

According to Pelphrey, a neuroscientist and expert on brain development and the study's principal investigator, the overarching aim of the ACE project is to lead the way in developing a precision medicine approach to autism.

"This study provides the foundation for a biological target to measure treatment response and allows us to identify avenues for future treatments to be developed," he said.

Van Horn added that study may also have implications for the examination, diagnosis, and treatment of other neurological disorders like Parkinson's and Alzheimer's.

"This is a new tool for measuring the properties of neurons which we are particularly excited about. We are still exploring what we might be able to detect with it," Van Horn said.

• Birth Defects
• Medical Devices
• Nervous System
• Brain Tumor
• Learning Disorders
• Disorders and Syndromes
• Autistic spectrum
• Brain damage
• Social cognition
• Rett syndrome
• Attention-deficit hyperactivity disorder
• Learning disability

Story Source:

Materials provided by University of Virginia College and Graduate School of Arts & Sciences . Original written by Russ Bahorsky. Note: Content may be edited for style and length.

Journal Reference :

• Benjamin T. Newman, Zachary Jacokes, Siva Venkadesh, Sara J. Webb, Natalia M. Kleinhans, James C. McPartland, T. Jason Druzgal, Kevin A. Pelphrey, John Darrell Van Horn. Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder . PLOS ONE , 2024; 19 (4): e0301964 DOI: 10.1371/journal.pone.0301964

Cite This Page :

Explore More

• Two Species Interbreeding Created New Butterfly
• Warming Antarctic Deep-Sea and Sea Level Rise
• Octopus Inspires New Suction Mechanism for ...
• Cities Sinking: Urban Populations at Risk
• Puzzle Solved About Ancient Galaxy
• How 3D Printers Can Give Robots a Soft Touch
• Combo of Multiple Health Stressors Harming Bees
• Methane Emission On a Cold Brown Dwarf
• Remarkable Memories of Mountain Chickadees
• Predicting Future Marine Extinctions

Trending Topics

Strange & offbeat.

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

April 17, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

Study identifies new metric for diagnosing autism

by Russ Bahorsky, University of Virginia

Autism spectrum disorder has yet to be linked to a single cause, due to the wide range of its symptoms and severity. However, a study by University of Virginia researchers suggests a promising new approach to finding answers, one that could lead to advances in the study of other neurological diseases and disorders.

The work is published in the journal PLOS ONE .

Current approaches to autism research involve observing and understanding the disorder through the study of its behavioral consequences, using techniques like functional magnetic resonance imaging that map the brain's responses to input and activity, but little work has been done to understand what's causing those responses.

However, researchers with UVA's College and Graduate School of Arts & Sciences have been able to better understand the physiological differences between the brain structures of autistic and non-autistic individuals through the use of Diffusion MRI, a technique that measures molecular diffusion in biological tissue, to observe how water moves throughout the brain and interacts with cellular membranes. The approach has helped the UVA team develop mathematical models of brain microstructures that have helped identify structural differences in the brains of those with autism and those without.

"It hasn't been well understood what those differences might be," said Benjamin Newman, a postdoctoral researcher with UVA's Department of Psychology, recent graduate of UVA School of Medicine's neuroscience graduate program and lead author of the new research paper. "This new approach looks at the neuronal differences contributing to the etiology of autism spectrum disorder ."

Building on the work of Alan Hodgkin and Andrew Huxley, who won the 1963 Nobel Prize in Medicine for describing the electrochemical conductivity characteristics of neurons, Newman and his co-authors applied those concepts to understand how that conductivity differs in those with autism and those without, using the latest neuroimaging data and computational methodologies.

The result is a first-of-its-kind approach to calculating the conductivity of neural axons and their capacity to carry information through the brain. The study also offers evidence that those microstructural differences are directly related to participants' scores on the Social Communication Questionnaire, a common clinical tool for diagnosing autism.

"What we're seeing is that there's a difference in the diameter of the microstructural components in the brains of autistic people that can cause them to conduct electricity slower," Newman said. "It's the structure that constrains how the function of the brain works."

One of Newman's co-authors, John Darrell Van Horn, a professor of psychology and data science at UVA, remarked that so often we try to understand autism through a collection of behavioral patterns which might be unusual or seem different.

"But understanding those behaviors can be a bit subjective, depending on who's doing the observing," Van Horn said. "We need greater fidelity in terms of the physiological metrics that we have so that we can better understand where those behaviors coming from. This is the first time this kind of metric has been applied in a clinical population, and it sheds some interesting light on the origins of ASD."

Van Horn said there's been a lot of work done with functional magnetic resonance imaging, looking at blood oxygen related signal changes in autistic individuals, but this research, he said, "goes a little bit deeper."

"It's asking not if there's a particular cognitive functional activation difference; it's asking how the brain actually conducts information around itself through these dynamic networks," Van Horn said. "And I think that we've been successful showing that there's something that's uniquely different about autistic-spectrum-disorder-diagnosed individuals relative to otherwise typically developing control subjects."

Newman and Van Horn, along with co-authors Jason Druzgal and Kevin Pelphrey from the UVA School of Medicine, are affiliated with the National Institute of Health's Autism Center of Excellence (ACE), an initiative that supports large-scale multidisciplinary and multi-institutional studies on ASD with the aim of determining the disorder's causes and potential treatments.

According to Pelphrey, a neuroscientist and expert on brain development and the study's principal investigator, the overarching aim of the ACE project is to lead the way in developing a precision medicine approach to autism.

"This study provides the foundation for a biological target to measure treatment response and allows us to identify avenues for future treatments to be developed," he said.

Van Horn added that study may also have implications for the examination, diagnosis, and treatment of other neurological disorders like Parkinson's and Alzheimer's.

"This is a new tool for measuring the properties of neurons which we are particularly excited about. We are still exploring what we might be able to detect with it," Van Horn said.

Explore further

Feedback to editors

Occupations that are cognitively stimulating may be protective against later-life dementia

7 hours ago

Researchers develop a new way to safely boost immune cells to fight cancer

Apr 19, 2024

New compound from blessed thistle may promote functional nerve regeneration

New research defines specific genomic changes associated with the transmissibility of the mpox virus

New study confirms community pharmacies can help people quit smoking

Researchers discover glial hyper-drive for triggering epileptic seizures

Deeper dive into the gut microbiome shows changes linked to body weight

A new therapeutic target for traumatic brain injury

Dozens of COVID virus mutations arose in man with longest known case, research finds

Researchers explore causal machine learning, a new advancement for AI in health care

Related stories.

Chemical regulates light processing differently in the autistic and non-autistic eye, new study finds

Apr 4, 2024

Autism develops differently in girls than boys, new research suggests

Apr 16, 2021

Researchers identify altered functional brain connectivity in autism subtypes

Dec 5, 2023

Scientists link genes to brain anatomy in autism

Feb 27, 2018

The hidden connection between adverse drug reactions and autism spectrum disorder

Sep 20, 2023

Guidelines for inclusive language in autism research

Sep 29, 2022

Recommended for you

How myeloid cell replacement could help treat autoimmune encephalomyelitis

Researchers discover dynamic DNA structures that regulate the formation of memory

Let us know if there is a problem with our content.

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

What Causes Autism? Understanding the Latest Research

FEATURED POSTS

Hanna Rue, Ph.D., BCBA-D, chief clinical officer

What does science say about what causes autism? The latest research indicates that a combination of genetic and environmental factors likely causes it.

There’s no simple answer, and scientists are still trying to develop better ones. “What caused my child’s autism? Was I to blame?” As David G. Amaral, Ph.D., a psychiatry and behavioral sciences professor at the University of California Davis wrote in 2017 in the journal Cerebrum , “Autism research has made tremendous progress over the last 20 years, but yet we still can’t provide definitive answers to most of these questions.”

What We Know for Sure

What we know for sure is that autism is a complex condition. It’s not caused by one single factor. The exact cause is still not fully understood, making it a subject of ongoing research.

Much of that research involves two main categories:

• Genetic factors: Scientists have found that certain gene changes, unusual gene combinations, and other genetic conditions can make a person more likely to have autism.
• Environmental factors: Since genetic factors don’t always lead to autism, that suggests that environmental factors could play a role. That could include factors, such as prenatal exposure to certain drugs or chemicals, complications during birth, or advanced parental age at the time of conception.

What Myths about Autism Science Has Debunked

Science has debunked several myths about autism, most notably the claim that vaccines cause autism. Large-scale studies have proven this theory to be false. Other debunked myths include the idea that autism is caused by parenting style or that it’s a mental health disorder . Autism is actually a neurological disorder resulting from differences in brain development.

It’s also worth noting that the prevalence of autism is rising, but this doesn’t necessarily mean more people are becoming autistic. An article in Scientific American explains that the bulk of the increase in autism rates stems from growing awareness of autism and better diagnostic methods.

Where Research Is Headed

The latest research in autism focuses on understanding the genetic and neurological aspects of the condition. Studies are further examining the perceptions of counselors in treating children with autism , which could help improve therapeutic approaches.

Other research is debunking more myths about vaccination risks related to autism . Still other researchers are looking into the intersection of autism in adulthood and the LGBTQ+ community . And some new research is looking into how certain proteins associated with autism interact with other molecules , shaping synaptic plasticity.

Our Understanding of Autism Is Evolving

Yet the most basic question — “What caused my child’s autism?” — may have no simple answer. Little by little, our understanding of what causes autism is evolving.

It’s becoming clearer that the causes of autism are multifaceted. While we might not have all the answers now, we are continuing to unravel the complexities of autism.

Subscribe or renew today

Every print subscription comes with full digital access

Science News

Aimee grant investigates the needs of autistic people.

Her research focuses on reproductive health care

Public health researcher Aimee Grant considers autism a cognitive difference, rather than a deficit.

Matthew Arthur

Share this:

By Saima S. Iqbal

April 19, 2024 at 9:30 am

Before becoming a researcher, Aimee Grant worked as a caregiver for six years in Cornwall, England, supporting autistic adults in group homes. But only more than a decade later, after befriending an autistic colleague at a sociology conference, did she realize she was autistic herself.

The stereotypical view of autism as a brain impairment more commonly found in men made it difficult for Grant to make sense of her internal world. From an early age, she struggled to pick up on important social cues and found the sounds and scents in her environment distractingly painful. But like many children in her generation, she says, she grew accustomed to either dismissing or disguising her discomfort. It was by listening to some of the stories of her female peers that Grant saw that the label could fit.

Receiving a diagnosis in 2019 prompted her to “reframe [my] entire life,” she says. She began working with her mind rather than against it. She no longer felt the same pressure to seem as nonautistic as possible with friends and family members, and she began to make use of accommodations at work, such as a light filter for her computer monitor. Today, as a public health researcher at Swansea University in Wales, Grant aims to uncover the lived experience of autistic people. Many scientists and clinicians see autism as a developmental disorder that hinders a person’s ability to understand and communicate with others. Grant believes that their work often obscures the heterogeneity of autism. And because many studies view autism as a disease, they overlook the reality that autistic people can feel more disabled by widespread misunderstanding and a lack of accommodations than by autistic traits themselves.

My work has a purpose: to make lives better for marginalized groups. Aimee Grant

In line with the thinking of the neurodiversity movement that emerged in the 1990s, Grant views autism as a cognitive difference, rather than a deficit: an alternative way of being in the world just as deserving of understanding and acceptance as any other. “I would say I’m disabled because of a range of different things, including being autistic,” she explains. (Grant has dyslexia and uses a wheelchair.) “But were I in a different environment, I don’t think I’d necessarily be disabled by being autistic — I think it’s those kinds of neurotypical expectations that can make life quite difficult.”

So Grant is asking a different research question: What might autistic people need?

She’s among a growing group of neurodivergent researchers whose science seeks to better serve its participants. Large surveys conducted in the United States and the United Kingdom  suggest that the majority of autistic people would choose to spend research dollars on actionable studies on well-being versus studies of the basic science of autism. At conferences and in private Facebook groups, researchers trying to shift science’s focus now number in the hundreds.

Grant’s current work centers on autistic mothers and parents with wombs. Through extensive surveys and interviews, she’s studied the barriers some autistic parents face in breastfeeding and identified ways clinicians can temper the pain of their patients’ pregnancy loss, such as by using clear and direct language or allowing partners or patient advocates into hospital rooms. On a YouTube channel she helped launch last year, autistic people share details of pregnancy and parenting . And she’s cofounded the Autistic Health Research Network , a small but international association of researchers seeking to better health care outcomes in the autistic community.

A passion for improving lives powers her research and outreach, says Karen Henry, a lecturer in midwifery at the University of Suffolk in England. Both Henry and Grant are part of the U.K.-based Maternity Autism Research Group . “I don’t know how she has enough hours in the day.”

Reimagining autism research

Grant’s work aims not only to serve study participants, but also to amplify their voices. By aggregating personal accounts, her research gives participants’ testimonies weight they often lack on their own, Henry says.

In one breastfeeding study, published last November in Maternal & Child Nutrition , Grant’s team surveyed 152 autistic birthing parents in the United Kingdom . The team found that nearly 70 percent of participants enjoyed breastfeeding overall. But 45 percent reported dealing with pain roughly half the time or more. One parent likened the feeling of the let-down reflex that gets breastmilk flowing to “an old-fashioned telephone ringing in my breasts.”

Still, most remained committed to breastfeeding, which the World Health Organization recommends women do exclusively for at least six months. The parents came up with creative solutions to ease their discomfort, including wearing clothing that exposed less of the most sensitive skin, wearing nipple shields and distracting themselves with videos or games on their phones.

Parents who received support from health care professionals, such as midwives or lactation consultants, tended to have a much easier time with breastfeeding. But nearly half of study participants had a negative interaction with at least one clinician, either struggling to access services, receiving incomplete or conflicting health information, or even feeling that their struggles were flat-out dismissed.

In the United Kingdom, just 1 percent of all mothers meet the WHO’s six-month recommendation, according to the latest available data from 2010. Grant and colleagues attribute this low rate to structural impediments, such as inadequate support for breastfeeding parents and aggressive campaigning by the formula industry, not to a lack of trying on the part of parents.

Grant says she has always wanted to “change perceptions about groups,” especially those criticized in the media, in regards to the broader ethos of her work, “to help the wider public recognize just how hard that group is working.”

To shed light on things that might not be known by policy makers, Grant has communicated her findings to the public in news articles and at conferences. The YouTube channel she helped launch now features more than a hundred clips of autistic parents and maternity experts sharing their expertise.

In 2022 Grant won a $3 million grant for an expansive study characterizing the broad reproductive health care needs of autistic people with wombs, from menstruation to menopause. The project, funded by Wellcome, will recruit 100 participants, interviewing them every six months for a total of five years.

“There’s a lot more questions than answers at the moment,” Grant says. Some of her team’s questions include: How can individuals manage the sensation of a period cramp or of ultrasound gel? What contraceptives do participants use, and what are their experiences? Are there differences in how autistic people sense and communicate bodily pain to health care professionals compared with what the research says of nonautistic people?

A project of such size and duration will identify areas where autistic people’s health care needs are not being met, Grant predicts. It may uncover positives of the autistic experience, as well as new avenues for research. Her team plans to keep the interviews loosely structured to “give people the space to talk about the things that are important to them.”

The team — made up entirely of autistic researchers — aims to capture the diversity within the community by partnering with autism organizations that serve individuals of various ethnic backgrounds and learning abilities, by paying participants for their time and for sign language interpreters if needed, and by allowing participants to choose to respond to questions through a video call, on the phone or via email. The researchers will also use their own neurodivergent perspectives to anticipate hurdles for participants: for example, putting text in fonts and colors that are easier to read or eliminating exclusionary phrases such as “autistic women,” which leaves out transgender and nonbinary people with wombs.

Grant is “really one of those practice-what-you-preach people,” says Rebecca Ellis of Swansea, one of four research assistants working on the project. “She is continually making sure that she can be as inclusive as possible and amplify the voices that get heard the least.”

Keeping an open mind

Grant doesn’t claim to have the single answer on what research on autism should look like; she’s committed to having an open mind. “I’m sure in 10 years we’ll have even more of a social model of autism,” she says, referring to a well-established view of autism as a disability constructed in large part by society, “and where we are now will seem outdated.” For now, she’s helping to get different perspectives in the room, collecting evidence for the theory that one’s environment can be more disabling than one’s predisposition.

Grant’s path to science may be part of what makes her work so unconventional.

Growing up, she did not expect to become a researcher. Her father was a firefighter, and her mother a housewife. In school, she just kept pursuing “the next thing that was interesting.” She attributes where she is today in large part to chance.

She pursued a Ph.D. in social policy at Cardiff University, where she studied competing political narratives around disability-benefit users, debunking a prominent myth that claimants were exploiting the welfare system. After completing that work, she needed to find a job near her home in order to reserve a spot on a waiting list for much-needed surgery. She worked in Cardiff as a research assistant, studying how well the National Health Service’s smoking cessation programs work, and then was asked to shift her focus to maternity. After her own autism diagnosis, she began to focus on autistic parents.

Along the way, she tended to be drawn to and stick with jobs with a social justice ethos. “My work has a purpose: to make lives better for marginalized groups,” she says. “It’s almost painful for me to do research that isn’t in those areas.”

More Stories from Science News on Health & Medicine

These windpipe cells trigger coughs to keep water out of the lungs

What can period blood reveal about a person’s health?

Teens are using an unregulated form of THC. Here’s what we know

Immune cells’ intense reaction to the coronavirus may lead to pneumonia

A protein found in sweat may protect people from Lyme disease

Heat waves cause more illness and death in U.S. cities with fewer trees

Bird flu has infected a person after spreading to cows. Here’s what to know

A new study has linked microplastics to heart attacks and strokes. Here’s what we know 

Subscribers, enter your e-mail address for full access to the Science News archives and digital editions.

Not a subscriber? Become one now .

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Sage Choice

How autism became autism

Bonnie evans.

King’s College London, UK

This article argues that the meaning of the word ‘autism’ experienced a radical shift in the early 1960s in Britain which was contemporaneous with a growth in epidemiological and statistical studies in child psychiatry. The first part of the article explores how ‘autism’ was used as a category to describe hallucinations and unconscious fantasy life in infants through the work of significant child psychologists and psychoanalysts such as Jean Piaget, Lauretta Bender, Leo Kanner and Elwyn James Anthony. Theories of autism were then associated both with schizophrenia in adults and with psychoanalytic styles of reasoning. The closure of institutions for ‘mental defectives’ and the growth in speech therapy services in the 1960s and 1970s encouraged new models for understanding autism in infants and children. The second half of the article explores how researchers such as Victor Lotter and Michael Rutter used the category of autism to reconceptualize psychological development in infants and children via epidemiological studies. These historical changes have influenced the form and function of later research into autism and related conditions.

The concept of autism was coined in 1911 by the German psychiatrist Eugen Bleuler to describe a symptom of the most severe cases of schizophrenia, a concept he had also created. According to Bleuler, autistic thinking was characterized by infantile wishes to avoid unsatisfying realities and replace them with fantasies and hallucinations. ‘Autism’ defined the subject’s symbolic ‘inner life’ and was not readily accessible to observers ( Bleuler, 1950[1911] : 63). Psychologists, psychoanalysts and psychiatrists in Britain used the word autism with this meaning throughout the 1920s and up until to the 1950s (e.g. Piaget, 1923 ). However, in the 1960s, many British child psychologists challenged the contentions about infantile thought assumed by Bleuler and created new methods to validate child psychology as a science, in particular epidemiological studies. ‘Autism’ was then completely reformulated as a new descriptive category to serve the needs of this new model of child development. From the mid-1960s onwards, child psychologists used the word ‘autism’ to describe the exact opposite of what it had meant up until that time. Whereas ‘autism’ in the 1950s referred to excessive hallucinations and fantasy in infants, ‘autism’ in the 1970s referred to a complete lack of an unconscious symbolic life. For example, Michael Rutter, a leading child-psychiatric researcher from the UK’s Maudsley Hospital who conducted the first-ever genetic study of autism, claimed in 1972 that ‘the autistic child has a deficiency of fantasy rather than an excess’ ( Rutter, 1972 : 327). The meaning of the word autism was then radically reformulated from a description of someone who fantasized excessively to one who did not fantasize at all.

This article traces this radical transformation of the concept of autism in Britain, exploring the reasons behind the shift and the impact that it has had on psychological sciences relating to infants and children. It argues that the change in the meaning of autism was part of a more general shift in Anglo-American psychiatric reasoning which sought to understand psychological problems through epidemiological studies rather than individual cases. The introduction of psychiatric classificatory models has previously been explored in relation to the Diagnostic and Statistical Manual ( DSM ), in particular the introduction of DSM-III in 1980 ( Grob, 1991 ; Mayes and Horowitz, 2005 ; Wilson, 1993 ). However, few people have explored this in relation to child psychology and psychiatry. This article examines the way that epidemiological methods shifted and morphed central concepts in these fields, in particular the concept of autism. It argues that the diagnostic practices required of psychiatric epidemiology in the 1960s continue to influence contemporary theories and descriptions of autism in Britain.

There has been a phenomenal increase in diagnoses of autism since the 1960s which has attracted the attention of many researchers ranging from psychiatrists and social scientists to literary analysts (e.g. Murray, 2008 ; Nadesan, 2005 ; Silverman, 2011 ). Victor Lotter’s first epidemiological study of autism posited a rate of 4.5 per 10,000 children but a 2006 Lancet article claimed a rate of 116.1 per 10,000 children in the UK and this figure continues to rise ( Baird et al. , 2006 ; Baron-Cohen et al. , 2009 ). Gil Eyal et al. have argued that, in the USA and many other western countries, diagnoses of autism rose after institutions for the ‘mentally retarded’ were closed down in the 1960s and children were integrated into new educational and social settings ( Eyal et al. , 2010 ). Changes in diagnostic methods from the 1960s to the 1980s meant that autism came to be associated with ‘profound mental retardation and other developmental or physical disorders’ thereby increasing the number of children who were considered to display autistic traits ( Wing and Potter, 2002 ). This explains why diagnostic rates of autism did not increase as much in France, where there was no great release of ‘retarded’ children from confinement in the 1960s and where children with developmental problems continue to receive institutional residential care up to the present day ( Eyal et al. , 2010 ).

Another reason why diagnoses of autism have risen in Britain and elsewhere is because the closure of institutions for ‘mentally retarded’ children led parents to campaign for better diagnosis and recognition of their children’s problems. Pressure groups such as the UK Society for Autistic Children (est. London 1962) worked hard to ensure that new treatment methods were developed to enable their children to adjust to the new social roles that they were being forced to adopt. This led to a growth in new behavioural treatment methods as well as a massive backlash against psychoanalytic styles of reasoning. Chloe Silverman’s recent book Understanding Autism has explored this history in the United States, detailing the work of Bruno Bettelheim and others working at the University of Chicago as well as the parents who challenged them such as Bernard Rimland and Rosalind Oppenheim. Silverman’s work shows how parents have since actively advocated new therapies and funded new research into the condition including genetic and environmental studies ( Silverman, 2011 ).

The closure of institutions for ‘mental defectives’ and the growth of parental advocacy groups help to explain the increase in cases of autism since the 1960s. However, it is important to position these changes in relation to broader shifts in the disciplines of child psychiatry, psychology and psychoanalysis. Epidemiological studies in child psychiatry experienced a period of expansion in 1960s Britain in the wake of the 1959 Mental Health Act. Autism had always been central to the study of childhood psychopathology in Britain and the introduction of epidemiological studies provided the concept with a new framework in which it has since flourished. ‘Autism’ appropriated new meanings and this meant that it came to be more easily diagnosed in children who previously would not have been considered to display that particular thought abnormality.

Child psychology and psychiatry in Britain and the introduction of autism prior to 1959

As Gillian Sutherland, Deborah Thom, Nikolas Rose and others have documented, the 1920s and 1930s in Britain witnessed a vast expansion of charitable and governmental services to cater for the psychological problems of children ( Rose, 1985 ; Sutherland and Sharp, 1984 ; Thom, 1992 ). In 1913, the Mental Deficiency Act was passed in England and Wales which ensured institutional care for all children identified as ‘mental defectives’. In that same year, Cyril Burt was appointed as the first official government psychologist in the UK and tasked with assessing the levels of psychological disturbance in the child population. He worked with infant welfare centres, school medical inspection officers and reformatory and industrial schools in order to do this ( Evans et al. , 2008 ). In the late 1920s, the Commonwealth Fund, an American philanthropic body, began to provide funds for the purposes of improving child guidance services in Britain ( Thom, 1992 ). Early child guidance clinics were used to direct child-rearing practices and to guide the behaviour of problem children ( Jones, 1999 ). The expansion of psychological services offered growing opportunities for child psychological professionals to observe and assess infants and children.

It was in this context that the terms ‘autistic’, ‘schizophrenic’ and ‘psychotic’ were introduced into the language of child psychological professionals in order to describe their child subjects. These were associated with a burgeoning discourse relating to the developing subjectivity of infants and children. The early 20th century had witnessed growing speculation about the nature of infantile and unconscious thought processes and their role in causing mental illness. Bleuler, Sigmund Freud, Carl Jung and Pierre Janet were all significant thinkers in this period who sought to unearth the forces that underlay psychological illness in the thoughts, experiences and traumas of childhood ( Ellenberger, 1970 ). A lot of this work was taken up readily by a new generation of child psychological professionals in Britain, such as Susan Isaacs, Melanie Klein and Mildred Creak.

When Bleuler had coined the term ‘autism’ in 1911, he attributed its etymological roots to Freud, and ultimately Havelock Ellis, through the term ‘ autoerotism ’ ( Bleuler, 1950[1911] ; McGuire, 1974 : 172–9). Freud had used this word in 1905 to describe hallucinatory thinking in conjunction with self-soothing in a stage of thinking which preceded the infant’s engagement with external reality ( Freud, 2001[1905] ). Bleuler also argued that the concept of autism was a refinement of Janet’s perte de la fonction du réel . In 1903, Janet had explained the function of reality as a synthesis of all psychological functions ranging from automatic functions at the level of the nervous system up to complex thoughts and actions. If the nervous system was weak, psychological tension would drop and an individual would lose the ability to synthesize these complex functions and also lose the sense of reality ( Janet and Raymond, 1903 ). He or she would then revert to a form of thinking which preceded the individual’s ability to conceptualize the sense of self.

Although Bleuler’s description of schizophrenia covered more than just autism – in particular, disturbances of attention, the will and the intellect – the concept was crucial to his description of the schizophrenic’s lack of contact with reality. According to Bleuler, when schizophrenics tried to conduct logical operations in thought, they were unable to draw upon all appropriate associations in the mind, thus leading to an unsatisfactory sense of reality. They therefore substituted this unsatisfactory reality with fantasies that more readily satisfied their affective needs. By blocking off the perceptive-sensory stimulations of the outside world, autistic thinking then came to obey its own special laws, which were no longer bound by the rules of logic ( Bleuler, 1950[1911] : 373). It was thinking that took place ‘in symbols, in analogies, in fragmentary concepts, in accidental connections’, and it was the source of both delusion and ‘crude offenses against logic and propriety’ (ibid.: 66–7). Although autism was pathological within schizophrenia, Bleuler always considered it to be merely ‘an exaggeration of a physiological phenomenon’ that was present in all humans, and which manifested itself in normal fantasies and wishes (ibid.: 374). Bleuler argued that the sense of reality was lost in schizophrenics only in relation to matters that threatened to contradict their complexes, a concept which had originally been developed by Jung who had claimed that it was analogous to what Janet called idée fixe subconsciente ( Ellenberger, 1970 ; Moskowitz, 2005 ). Freud would later expand on the way in which autoerotic thinking and, what he termed, primary narcissism were transformed via the onset of the Oedipus complex.

Bleuler’s, Freud’s and Janet’s interest in the symptoms of autism and autoerotism in adults was shared by many other French alienists who had referred to aspects of autism as ‘autophilia, egocentricity, ego-hypertrophy, and augmentation du sens de la personnalité ’ ( Bleuler, 1950[1911] : 373). Some French writers, such as Henri Claude of the Hôpital Sainte-Anne in Paris, criticized Bleuler’s direct association between autistic thought and the loss of the sense of reality ( Claude et al. , 1924 ). However British researchers such as Creak, Klein and Isaacs followed Freud and Bleuler in linking autistic and autoerotic thought with hallucinatory thinking. They also drew substantially from the work of Jean Piaget in making these claims.

In 1922, Piaget gave a paper at the International Conference on Psychoanalysis, Berlin, entitled ‘ La pensée symbolique et la pensée de l’enfant ’ where he put forward his theories on the way that infants developed a relationship to reality via their everyday interactions with people and objects ( Chapman, 1988 : 121). Drawing from Bleuler and Freud, he claimed that the pre-verbal stages of children’s thought could be described as ‘autistic’ or ‘symbolic’. During this stage of thinking, children could not follow logical rules and did not think conceptually and there was a predominance of visual imagery in their minds ( Piaget, 1923 : 273–304). These thought processes subsided as the infant became more aware of the concrete objects and reality surrounding him or her. Piaget drew direct analogies between infantile thinking and unconscious symbolism as described in psychoanalytic theory ( Vidal, 1994 : 209–10). He claimed that ‘autistic’ and ‘symbolic’ thought were both characterized by three distinctive features, namely, ‘ absence de suite logique, predominance de l’image sur le concept, et inconscience des connexions qui relient les images successive entre elles’ [an absence of logic, a predominance of visual imagery over conceptual thought, and no awareness of the connections that can be made between visual perceptions] ( Piaget, 1923 : 290–3, 303–4). Piaget also linked the concept of autism directly to the child’s progressive attempts to engage with reality ( Vidal, 1994 : 209–10). He developed psychological tests which measured children’s perception and self-awareness. In his 1929 publication The Child’s Perception of the World , he reported the results of tests in which he had questioned children on their beliefs about the physical world and argued that their thought developed from primitive magical imagination through to logical reasoning. Drawing attention to Freud’s work on mental economy, he argued that when adults thought symbolically, they ‘condensed’ concepts and ‘displaced’ one image or concept onto another because they experienced a reversion to primary autistic thinking in which no distinction was made between the various external stimuli that bombarded the infant in her or his daily life ( Piaget, 1923 ).

In Britain, child psychological professionals introduced these theories in the 1920s and 1930s. Freud’s work had already developed an outlet in the British Psycho-Analytical Society, established by Ernest Jones in London in 1913. Melanie Klein, a Viennese émigrée and child analyst who had joined the society in 1926, was extremely influential on the psychological treatment of children in Britain ( Steiner, 1991 ). In 1929 Klein published a paper on personification in the play of children in which she argued that if instinctual wish fulfilment dominated over a child’s recognition of reality then the child could be described as experiencing a type of ‘psychosis’ ( Klein, 1929 ), a term which Freud had used in 1894 to describe ‘hallucinatory confusion’ ( Freud, 2001[1894] ). In 1930, she argued that schizophrenia and psychosis should be diagnosed more often in children as this would help child psychologists to understand infantile thought and its extreme pathologies ( Klein, 1930 ).

Susan Isaacs supported Klein’s ideas about the importance of describing hallucinations and fantasies within infantile thought and also adopted Piaget’s theories on child development. Isaacs was also an influential figure in child psychology in Britain, having supervised Burt’s advanced psychology students at University College London and lecturing widely on psychology and psychoanalysis before being appointed as head of the Department of Child Development at the University of London’s Institute of Education in 1933. She served on the editorial board of the British Journal of Educational Psychology and the British Journal of Medical Psychology ( Sayers, 2001 ). In addition, she had been greatly influential in guiding government policy on childcare and education; for example, giving evidence to the Hadow Committee on Infant and Nursery Schools in 1933 and later the Home Office Care of Children Committee in 1945 (ibid.: 219; Wooldridge, 1994 : 133–4).

Mildred Creak was another important British child psychological professional who sought to develop ideas on severe psychopathology and hallucination in infancy. She had trained in medicine at University College Hospital, London, and was appointed as head of child psychiatry at the Maudsley Hospital in 1931. Writing in 1937, she argued that although ‘normal thought processes, at an early age, recapitulate those primitive and archaic forms so often seen in schizophrenics’, childhood schizophrenia should be conceptualized as a ‘reaction’ which disturbed the normal development of infantile thought leading to problems in the formation of intellect and motor coordination. She claimed that in schizophrenic children, one could observe a ‘tendency to fragmentation and interruption in the thinking processes’ as well as ‘dereistic thinking’, which Bleuler used as a synonym for autistic thinking. 1 Her 1937 study was the first to present long descriptions of pre-pubescent children who developed what she understood as a ‘schizophrenic reaction’. Along with Klein and Isaacs, she paved the way for more detailed discussions on the way that severe psychopathology should be conceptualized in infants and children.

The Second World War increased the opportunities for child psychologists to study the psychological problems of infants and children. In Britain, over 1 million unaccompanied children were evacuated from cities and many high-profile psychologists and psychoanalysts including Klein, Isaacs and John Bowlby established the Cambridge evacuation survey to study the effects of such major environmental changes (B. Harris, 1995 ; Rose, 1999 : 165). At the same time, Anna Freud established wartime nurseries in London for children who could not be evacuated ( Burlingham and Freud, 1943 ). Klein, Isaacs, Bowlby and Anna Freud employed theories of unconscious processes to explain pathological thought in the infants that they observed.

It was widely thought that ‘maternal deprivation’ could help to explain why some children developed pathological thinking patterns while others did not. In the early 1940s in the USA, Lauretta Bender from the Bellevue Hospital, New York, and William Goldfarb from the Ittleson Center for Child Research, New York, conducted studies on maternal deprivation which echoed the studies on evacuated children in the UK. All of these studies drew similar conclusions. As Bowlby put it, ‘with monotonous regularity each put his finger on the child’s inability to form relationships as being the central feature from which all other disturbances sprang’ ( Bowlby, 1951 : 34). This was said to affect the child’s ability to conceptualize as well as his or her intelligence and capacity for relationships. Bowlby and Bender, in particular, thought that these disturbances affected the unconscious mental processes of these children causing them to retreat from the outside world.

In the early 1940s, major disagreements arose as to how, exactly, the infant’s early relationships affected her or his thinking processes to cause psychopathology. Klein and her supporters claimed that they had found evidence for subjective responses to instincts in infants that presupposed the existence of complex mental mechanisms which could control, redirect and repress unconscious instinctual urges from the very first moments of life. Early in 1943, Susan Isaacs described in detail her thesis that children experienced ‘phantasies’ in relation to their early experiences which led them to repress or divert internal forces and drives which could manifest problems in later life. Isaacs claimed that from the moment that an infant experienced an instinctual urge, he or she also had the capacity to fantasize about that urge and to imagine the direction it might take. As Isaacs put it, ‘phantasy is the mental corollary, the psychic representative of instinct’. Isaacs argued that ‘every impulse, every feeling, every mode of defence is expressed and experienced in such a specific phantasy, which gives it mental life and shows its specific direction and purpose’ ( Isaacs, 1991[1943] : 277–8).

Fantasies could be associated with libidinal instincts or drives as well as destructive instincts and impulses. Using evocative language, Isaacs claimed that if the child was feeling ‘desires towards his mother’, he would experience these as ‘I want to suck the nipple, to stroke her face, to eat her up, to keep her inside me, to bite the breast, to tear her to bits, to drown and burn her, to throw her out of me’ ( Isaacs, 1991[1943] : 277). Infants were also thought capable of altering and prohibiting their unconscious desires ( Heimann, 1991[1943] ). Within this model, it was possible to understand how infants could employ hallucinations in a pathological way which prevented them from developing a satisfactory relationship to reality. In other words, according to Klein and Isaacs, infants were never wholly ‘autoerotic’ or ‘autistic’ and thus some forms of hallucination, even in infants, could concern their relationships to others. Psychopathology could thus be created, via relationships, in infants from the very first moments of life.

The critics of the Kleinian analysts argued that they were attributing advanced psychical processes to infants without giving thorough evidence and explanation for these claims. Anna Freud argued that after an infant was born there was a period of roughly 6 months when the child was inherently ‘narcissistic and auto-erotic’. During this phase, the aim of an instinct was fundamental but the object of that instinct was ‘only dimly taken into account’. In this state ‘satisfaction counts for everything and objects count for nothing’. The child had no awareness of the effects of his actions on others, had no sense of guilt or anxiety over his actions, and no sense of loss (Freud in King and Steiner, 1991 : 418–21). Anna Freud’s position was that environmental factors and relations could affect a child to cause psychopathology and reversion only from 6 months old.

Although the precise concept of ‘autism’ was rarely mentioned in these discussions, the descriptive concepts of ‘autoerotism’ and ‘primary narcissism’, a term which had been developed by Sigmund Freud as a response to Bleuler’s concept of autism, were discussed frequently. These discussions of whether, and at what age, one could attribute desires and thoughts to infants were never concluded. Yet they continued to exist as important conceptual problems in child psychology because they concerned the origins of relational thought. Cyril Burt and other educational psychologists in the 1940s also debated how to attribute mental activity and thoughts to infants, clashing dramatically with behaviourists such as J. B. Watson who argued that it was not the vocation of psychologists to describe the thoughts that they imagined infants to have ( Watson, 1925 ; Burt, 1941 ).

While these controversies were still raging in Britain, Leo Kanner from Johns Hopkins University Hospital in Baltimore claimed that he had identified a unique psychological disorder in children characterized by ‘extreme autism, obsessiveness, stereotypy, and echolalia’. He referred to this as ‘inborn autistic disturbances of affective contact’, claiming that the symptoms brought ‘the total picture into relationship with some of the basic schizophrenic phenomena’. Unlike Klein and Isaacs, Kanner was reserved in the attribution of unconscious thought processes and a symbolic life to infants. Instead, he described a list of cases in which he had observed similar symptomatology. Kanner’s children were described as having a ‘good relation to objects’, in particular those ‘that do not change their appearance and position, that retain their sameness and never threaten to interfere with the child’s aloneness’. On the other hand, the children’s relation to people was ‘altogether different’ and Kanner described instances in which the children would barely notice when other people entered a room. He also noted that these children tended to use language in a very literal fashion and that they failed to relate to other people physically ( Kanner, 1943 ).

Kanner’s interest in children who found it difficult to relate to others echoed the general interest of all child psychiatrists in the period. However, his article was significant because it presented a new way to describe infantile thought. Rather than attributing complex unconscious thought processes to children that he observed, he simply described the behaviour of a group of children with similar symptoms. He used the word ‘autistic’ to convey the fact that the children appeared not to be engaged with their external environment. However, this descriptive mode in child psychiatry was not standard at this time and many other child psychological professionals in both Britain and the USA continued to employ the concepts of autism in conjunction with autoerotism, primary narcissism and symbolic thinking to understand infantile psychopathology and problems with developing relationships.

Postwar conceptualizations of autism and infant psychopathology

After the war, the controversies over how to describe infantile thought continued. The diagnoses of schizophrenia, psychosis and autism in children were largely interchangeable during the 1940s and 1950s. In the USA, Bender and others employed a Kleinian model to understand infant and child psychopathology and focused on schizophrenia as the central psychopathological problem of childhood. Bender was an important figure in the development of perceptual tests for children. In 1947, she published a study on ‘one hundred schizophrenics’ who had attended the Children’s Department at Bellevue during the period 1937–47. She defined childhood schizophrenia as

… pathology in behavior at every level and in every area of integration or patterning within the functioning of the central nervous system, be it vegetative, motor, perceptual, intellectual, emotional or social. ( Bender, 1947 : 40)

She claimed that childhood schizophrenia struck ‘at the substratum of integrative functioning or biologically patterned behavior’, a definition which had resonances with Janet’s perte de la fonction du réel . Bender believed that child schizophrenics became fixated on the stage of infancy characterized by ‘internalised objects’ ( Bender, 1947 : 51). She also claimed that they were particularly driven by infantile aggression. This caused ‘condensation or the superimposing of many levels of thinking and psychological problems’. Whereas in normal children, symbolism became abstract and appeared only in dreams, fantasies and fairy tales, the symbolic thought of schizophrenic children remained concrete and structured their entire thought disorder. She drew from Arnold Gessell’s Embryology of Behaviour (1945) to argue that psychotic children retained primitive embryological motor functions that prevented the integration of mental functions and the establishment of an ego and a relation to reality. Psychotic children retained ‘primitive homeostatic control and primitive patterns of sleep and wakefulness with waning states of consciousness’ ( Bender, 1953 : 674–5).

In the UK, Elwyn James Anthony and Kenneth Cameron at the Maudsley Hospital employed similar theories of the infantile unconscious to understand childhood schizophrenia and autism. In 1953, they opened a ‘psychotic clinic’ which received referrals of the most severe cases of psychological disturbance in children from across Britain. Anthony, who had trained under Aubrey Lewis and Jean Piaget ( Hersov, 1986 ; Institute of Psychiatry, 1951: 13), argued that observations of these children could be used to formulate a general theory of infantile thought and psychology. In 1958, the European Journal of Child and Adolescent Psychiatry published Anthony’s ‘An Aetiological Approach to the Diagnosis of Psychosis in Childhood’ which was very well received (J. K. Wing, 1966 ; Rutter, 1966 : 16).

Anthony argued that the age at which a child developed autism or psychosis affected the form that the disorder took. He believed, as Anna Freud did, that ‘every infant begins its psychological life in an autistic state’. Using a concept borrowed from Sigmund Freud’s Beyond the Pleasure Principle , Anthony employed a ‘barrier hypothesis’ to explain the development of different types of autism in children. He argued that during normal development, the constitutional barrier which protects the infant is supplemented by a maternal barrier, which eventually gives way to an ‘autonomous ego barrier’. This barrier enables the child to focus and not to be distracted by every passing stimulus. He argued that in cases of primary autism, infants developed a barrier that was ‘abnormally thick’ and that the infant then went on to block all sensations to the extent that ‘he fails to emerge from his primary narcissism’. In cases of secondary autism, the constitutional barrier is ‘abnormally thin’ allowing an excessive amount of stimulation to affect the psychotic child’s ego. In this situation, the infant then develops his own secondary psychotic barrier which then blocks all stimulation ( Anthony, 1958a : 212). He argued that within all cases of childhood psychosis and autism, there were ‘components of three basic conditions of malfunctioning’: an inability to form a coherent and stable sense of self; an inability to ‘cathect’ internal experiences accurately; and ‘a confusion of self and non-self and disturbances in the perception of the self’. Anthony borrowed the term ‘a-dualism’from Piaget in order to define this last problem. He employed standard Piagetian tests in order to confirm his theories (ibid.: 223–4).

Anthony’s aim was to (re)integrate psychoanalytic theory into the Piagetian scheme of subjective development in order to enable the detailed description of both normal and abnormal infantile thought. He claimed that the initial stages of a child’s life were characterized by primary narcissism or egocentrism where ‘the self and the environment are one and there are no permanent external objects’ (Anthony, 1957b: 262). The emergence of self-awareness came about after the child, as organism, ceased to function through pure reflex action and came to use ‘inventive action’ to grasp and direct objects in space. This emergent intellectual ability was paralleled with a new emotional ability to relate to objects. As he described it, ‘the child was only able to proceed to a full emotional relationship with objects after he had rendered them permanent and substantial’ (ibid.: 258). The ‘psychotic ego’ failed to draw a distinction between inner fantasy and outer reality resulting in an ‘asymbolic’ or autistic state of mind ( Anthony, 1958a : 212) ( Figure 1 ).

Table by E. J. Anthony, ‘The psychotic ego with its defects and defences’, first printed in Anthony (1958a) .

Anthony claimed that the causes of childhood psychosis consisted of ‘constitutional, organic, genetic and psychogenic determinants and possibly some still unknown factor’ ( Anthony, 1958b : 93). He strongly urged against any ‘monocausal’ view of the condition, especially that which placed excessive emphasis on ‘schizophregenic’ or ‘psychotogenic’ parents.

The basic problem which Anthony, Klein, Isaacs and Creak sought to address from the late 1920s to the late 1950s was that of the infant’s developing relationship to reality. All of these UK-based theorists assumed that hallucinatory thinking preceded the establishment of relationships with other objects or individuals. Furthermore, all of them established their theories through the study of individual children whom they had observed and/or treated themselves. Their understanding of autism was framed by a broader disciplinary-wide agreement that developmental psychology was a science that tracked the emergence of subjectivity. If they did employ basic statistical methodologies, these were used as an adjunct to these theories. The rest of this article explains how epidemiological studies were employed from the late 1950s in order to radically overturn this model of child development and the concept of autism which supported it.

The 1959 Mental Health Act, epidemiology and the radical transformation of the concept of autism

The 1960s witnessed major transformations in the care of the mentally ill in Britain. In 1959, the British Government passed the Mental Health Act which discredited most legal powers that had previously compelled the mentally defective and insane to institutional treatment. It abolished the Board of Control that had previously managed this process, thereafter making local authorities responsible for institutional and community care. The 1959 Act led to major administrative problems resulting from the large-scale closure of institutions for individuals with mental abnormalities. This led to the development of new social-scientific methods as it became paramount to demarcate the mental problems and needs of children and adults who had previously been confined but were now being integrated into the majority population. One of the most significant fields to develop following the closure of institutions was the technique of psychiatric epidemiology.

In 1958, the ‘Social Psychiatry Research Unit’ was opened at the Maudsley Hospital in anticipation of the Mental Health Act. The unit was funded by the Medical Research Council (MRC) and became a world-leading centre for epidemiological and statistical research in mental health, in particular relating to schizophrenia and autism. The psychological experimentation that was emerging from the unit in this period was greatly influenced by the work of Hans Eysenck who was then heading the psychology department. Eysenck and influential colleagues such as Jack Tizard, Beate Hermelin and Neil O’Connor conducted statistical analyses that were focused entirely on behavioural measures. Eysenck claimed that clinical research must be experimental and ‘scientific’ by which he meant that it should be based on direct observation and not on any kind of self-analysis ( Derksen, 2001 ). He argued that Freudian analytic concepts concerning the unconscious were speculative impressions and he challenged the efficiency of psychoanalytic psychotherapy as a curative technique ( Eysenck, 1990 : 127–9).

Many researchers realized that autism and childhood schizophrenia were important concepts within the theory of children’s psychological development which offered much potential for the development of statistical methodologies. In 1961, Mildred Creak set up a working party to identify the key features of childhood schizophrenia and to establish a firm basis for research in childhood psychopathology ( Creak, 1964 ; Lotter, 1966 ). Creak’s working party consisted of 13 members including Kenneth Cameron; Sylvia Ini from Great Ormond Street Hospital; Dr Guy Mitchell from the Tavistock Clinic; Dr Ronald MacKeith from Guy’s Hospital; and Frank Orford, a clinical psychologist who had previously worked at the Fountain Hospital for mentally defective children. The committee argued that there were 9 key features of ‘schizophrenic syndrome in childhood’ which were:

• gross and sustained impairment of emotional relationships with people
• apparent unawareness of his own personal identity
• pathological preoccupation with particular objects
• sustained resistance to change in the environment
• abnormal perceptual experience
• acute, excessive and seemingly illogical anxiety
• speech may have been lost or never acquired
• distortion in motility patterns
• a background of serious retardation in which islets of normal, near normal, or exceptional intellectual function or skill may appear ( Creak, 1961 : 889–90).

Creak argued that if all psychiatrists could agree on the same ‘diagnostic features’ this ‘would clear the way towards a common understanding and recognition of the phenomenological composition of the syndrome’ to enable population-based studies.

In 1963, Hermelin and O’Connor from the MRC Unit used Creak’s 9 points to bring together a group of research subjects in whom they could test ‘sensory dominance’. The closure of mental deficiency institutions had generated a large supply of ‘subnormal’ children who were used as controls in these experimental situations. Whereas intelligence tests were by then well established as psychometric instruments, measures of psychopathology in children were new. Hermelin and O’Connor worked with staff at Botley’s Park Hospital for the mentally handicapped in Chertsey and St Lawrence’s Hospital in Cornwall to select ‘autistic’ children based on Creak’s list and ‘subnormal' children identified through intelligence tests. Both groups were matched for IQ levels (mean 40) so that the only difference between them was that the group deemed ‘autistic’ was ‘severely disturbed’. The children were rewarded if they gave correct responses to tactile, auditory and visual stimulation. ‘Autistic’ children were found more likely to respond to tactile and visual stimulation than auditory stimulation although they could be taught to respond to sound if they were rewarded ( Hermelin and O’Connor, 1963 ).

Hermelin and O’ Connor attempted to develop Anthony’s theories on sensory dominance in autistic children but they did so by using behavioural tests and statistical methods as their theoretical model, rather than internal psychology. They suggested that the developmental process in all children was driven by a ‘hierarchical structure of sensory systems’. At first, an infant responded to ‘interoceptive and visceral sensations’ and these were later superseded by a dominance of tactile and kinaesthetic sensations. Finally, the auditory and visual sensory systems became dominant. These developments were paralleled by the ‘integration of different sensory information’ in order that ‘stimuli to one sense can be readily recognised and interpreted in another’. It was argued that ‘psychotic’ or ‘autistic’ children found it harder to inhibit earlier, more primitive, responses than controls. They developed a spontaneous preference for tactile and visual stimuli and found it difficult to renounce this preference when presented with auditory stimulation. This distinguished them from their subnormal controls who did not have any preference although they still found it difficult to learn (Hermelin and O’Connor, 1967). These tests appeared to provide psychological proof that ‘autistic’ children remained stuck in early stages of development in a way which was unique and not related to intelligence.

In 1965 , Michael Rutter was appointed as Senior Lecturer in Child Psychiatry at the Institute of Psychiatry, taking over the post left vacant by Anthony in 1958 (Institute of Psychiatry, 1965). Rutter had trained in medicine at Birmingham and specialized in psychiatry at the Maudsley under Aubrey Lewis and Eysenck. In 1961, he studied with the comparative psychologist Herb Birch and the psychiatric epidemiologist Ben Pasamanick. Along with Pasamanick, Rutter was interested in using epidemiological methods in order to determine causation rather than simply to measure prevalence rates ( Rutter, 2001 ). In 1965, he published a manifesto arguing for the classification of all childhood psychiatric disorders, asserting that ‘until a disorder can be identified and characterised, it cannot be adequately studied’ (1965: 71). He thereafter worked closely with the World Health Organisation in developing a multi-axial system of psychiatric diagnoses (ibid.; Shaffer, 2001 ). In line with these efforts, Rutter initiated a study of childhood autism in a cohort of children in Aberdeen and encouraged further population studies of this condition in order to assist the general field of child psychiatry. At the same time, Rutter and Tizard embarked on a major study of the complete rates of psychiatric disorder in all children resident on the Isle of Wight ( Rutter, Tizard and Whitmore, 1970 ). According to Rutter, epidemiological studies could gather similar research subjects who could help determine the causes of autism and other disorders thereby eradicating the need for speculative child psychoanalysis and psychology.

It was O’Connor, J. K. Wing and Victor Lotter from the MRC Unit who designed the first mass survey of an entire population cohort in order to generate a percentage figure for the rate of autism in the general population of Britain. Lotter, the principal author, drew from the Creak working party’s criteria for his epidemiological study but argued that the 9 points needed to be adapted because they were not confined to observations of children’s behaviour but included subjective opinions about children’s feelings. Creak had claimed that it was ‘impossible’ to use purely behavioural criteria ‘if we were to convey what we all felt to be the heart of the matter – namely the presence of an impaired capacity for human relationships’ ( Creak, 1961 : 889–90). However, Lotter, following Rutter, considered that clear-cut purely behaviouristic criteria were paramount to the development of that epidemiological research on autism despite the fact the psychological state that was being described concerned the capacity to relate to other people. Lotter therefore discarded the category ‘apparent unawareness of his own personal identity’ and subsumed it within other behavioural measures. He also replaced the presence of ‘islets of ability’ with objective test scores ( Figure 2 ). He then developed a list of statements which were used in order to identify children with autistic conditions. This form was issued to teachers of 76,388 children between the ages of 8 and 10 attending schools in the Middlesex area. Children identified by teachers were then further assessed to confirm their autism.

Table by Victor Lotter, ‘Mean percentage scores on 24 behaviour items’ ( Lotter, 1966 ).

Lotter claimed that he had developed ‘adequate behavioural descriptions’ for the condition of autism. These descriptions would encapsulate the symptom of autism, which he understood as a behavioural parameter and not a disease entity. As he put it:

… the adjective ‘autistic’ was used in this study as a convenient descriptive label. It is important to note that the term was not intended to refer only to Kanner’s syndrome of ‘infantile autism’, and in what follows is used without qualification to refer to all children who met the behaviouristic criteria used to select cases. References to ‘autistic behaviour’ are to be similarly interpreted. ( Lotter, 1966 : 125)

In other words, Lotter’s study was a quantification of the description of ‘the autistic’ within a total population. He reported the prevalence-rate to be 4.5 per 10,000 of the population ( Lotter, 1966 ).

The requirement for ‘precise behavioural criteria’ which epidemiological studies demanded encouraged new perspectives and descriptions of autism. Because this concept had been so central to general developmental psychology, its re-formation within the field of psychiatric epidemiology led new researchers to reconceptualize the central issues of that science. However, Lotter and colleagues reframed the topic of a child’s developing abilities to relate to others as purely a function of her or his behaviour. This model differed widely from those based on theoretical descriptions of a child’s imagined relationships to others such as in the work of Klein, Isaacs and Anthony. Instead of measuring child development and its anomalies via theoretical models of an individual child’s successive attempts to engage with reality through his or her relationships with people and objects, these studies measured child development and its anomalies as behavioural variables within a total population that represented the norm. At the same time, the study of an individual’s response to stimuli was replaced with the statistical analysis of a population’s response to stimuli. The study of human relationships was not written out of this model because human relationships could still be observed as phenomena. However, questions about how, why, or when relationships became pathological, particularly those concerning the child’s capacity to imagine, hallucinate, or fantasize about others, were absent from this new theoretical model.

The disappearance of hallucinations

The integration of children with intellectual disabilities into schools following the 1959 Mental Health Act had led to the employment of increasing numbers of educational psychologists. In 1967, there were 375 full-time educational psychologists employed by local authorities but by 1972, this number had risen to 638 (B. Harris, 1995 ; Wooldridge, 1994 : 316). In 1979 this figure had risen to 935 and in 1983 it had increased to over 1,000 (Hansard, 1983). This new professional group increasingly came to rely on psychiatric measures for child psychological disorder. Furthermore, the early 1970s in the UK saw a major push to increase numbers of speech therapists employed by health authorities following the publication of the Report of the Committee of Enquiry into Speech Therapy Services (the Quirk Report) which reported that well over 300,000 individuals in the UK were in need of speech therapy services and that 270,000 of these individuals were children ( Lindsay, 1984 ). Again these were aftershocks of the closure of deficiency institutions and the need to integrate children who had previously been isolated. The Society for Autistic Children began to set up its own schools in the early 1960s, which were exclusively for autistic children, and also campaigned to the Ministry of Education to regard all autistic children as ‘educable’. 2 The need to integrate all children within the same educational framework also encouraged their integration in a unified theoretical framework concerning the development of their thought.

Many statistical study designs from the 1960s and 1970s were drawn up to analyse and assess childhood schizophrenia and its causes, all of which precluded the possibility of hallucinatory thought in infants. For example, in 1971, Israel Kolvin, from the Nuffield Child Psychiatry Unit in Newcastle, sought to test Anthony’s hypothesis that psychotic disorders in childhood are dependent on the age at which the process begins. In order to do this, he separated childhood psychotics into groups relating to age of onset and then divided up the ‘phenomenology’ of the condition according to these different groups. What was significant in the planning of this exercise was the implementation of ‘rigorous criteria’ to ensure that the children could be compared with one another equally. As with other social-scientific models, the rigorous quality of the data depended on its ability to be examined and then replicated by numerous researchers.

Kolvin argued that researchers should never attribute fantasies to children who did not have the words to describe these themselves. He explained his approach as follows:

Both groups of psychotics were examined for hallucinatory phenomena … Gazing round in a distracted manner or looking as if they were hearing voices were insufficient. In addition, at some time the child must have given an account of hallucinatory phenomena. ( Kolvin, 1971 : 22)

These criteria were exceptionally rigorous, to the extent that they were narrowly conceived, when concerning children who could not talk or had very limited language abilities. Nevertheless, they were regarded as essential to the progression of statistical methods in child psychiatry. Not surprisingly, Kolvin found that children with ‘late-onset psychosis’ were ‘commonly hallucinated’, whereas those with early-onset psychosis, in the first 3 years of life, were more likely to suffer from ‘severe speech delay and many speech anomalies’ as well as ‘stereotyped movements’ and ‘poor relationships’ rather than hallucinations ( Kolvin, 1971 ). Kolvin’s study excluded the possibility that autism in infants and young children was accompanied by hallucinatory thinking of any form. His description of autism was the direct opposite of that which had first been put forward by Bleuler and which had been supported by Creak, Klein and Anthony from the late 1920s to the 1960s. However, it is this model of ‘early-onset psychosis’ which later became dominant in descriptions of the concept of ‘autism’, which is ironic because ‘autism’ had originally been used precisely to describe normal early infantile thought.

Kolvin’s work has been extremely influential and all researchers who have followed his study design have reached similar conclusions (e.g. Rapoport et al. , 2009 ). These researchers have increasingly focused on the study of language and increasingly regarded autism as a ‘communication disorder’ rather than a ‘psychotic disorder’. In 1967, Rutter and others conducted a follow-up study of 63 children who had been diagnosed with early-onset psychosis and argued that that although a few of the children ‘behaved in an odd manner which gave rise to the suspicion that they were having hallucinatory experiences … in none was there convincing evidence of hallucinations, and no child with speech described sensations or happenings which were hallucinatory’ ( Rutter, Lockyer and Greenfeld, 1967 : 1190). A 1972 quote from Rutter summarizes the problems with using the term autism which followed the introduction of statistical and epidemiological methods: ‘ autism means a withdrawal into fantasy but this is not what happens in the syndrome of autism ’ ( Rutter, 1972 : 327).

Of course, what constituted ‘convincing evidence’ of the existence of hallucinations in children differed widely among practitioners. Whereas psychoanalytically influenced psychologists inferred hallucination from children’s actions, Rutter and the Maudsley researchers thought that this kind of inference should be eliminated from all research inquiries. This was not because they were averse to the idea of hallucinations in infants and children but rather because such claims would have disrupted the accuracy of epidemiological studies. In general, researchers would follow Kolvin and Rutter in claiming that unless a child described hallucinatory thoughts using speech, she or he could not be assumed to experience hallucinations. Whereas this contention would not eliminate the concept of hallucination in adult psychiatry, because linguistic descriptions of hallucination still counted as a form of behaviour, it completely transformed child psychiatry.

Autism as communication disorder

As autism became increasingly detached from hallucinations and fantasy, psychiatric researchers looked for new ways in which to identify the problem in individual clinical cases. Perhaps unsurprisingly, these researchers turned to the study of language to identify the central ‘cognitive deficit’ of autism. This reflected the growth of the ‘cognitive’ movement in psychology ( Nadesan, 2005 ). In 1968 , Rutter had argued that Creak’s 9 points for autism could be replaced with 3 key features, namely ‘profound abnormalities of language development, a variety of ritualistic and compulsive phenomena … [and] a particular variety of disturbance in interpersonal relationships’ (1968: 4). Rutter, Hermelin, J. A. M. Martin and Lorna Wing all conducted studies on the language used by autistic children in the late 1960s and 1970s which developed Hermelin and O’Connor’s view that sensory deficits in infancy led to the development of unusual language features in autistic children ( Martin, 1971 : 295). These language abnormalities or differences then came to be a defining feature of the new concept of ‘autism’ in its new psychological metamorphosis, which followed its radical strip-down to behavioural measures in the 1960s. The main purpose of these studies was to compare the language of autistic children with that of children who had other problems such as executive or receptive aphasia and partial blindness or deafness. Although these researchers did not know the exact form of the central sensory disorder which caused autism, they were all united in the view that the condition was not caused by emotional reactions or hallucinations but was instead characterized by a deficit in certain aspects of linguistic thought.

These changes were contemporaneous with a wider interest in the ‘communication’ problems of children as opposed to their emotional problems (e.g. Franklin, 1965 ). In 1975 , Rutter, Lawrence Bartak and Anthony Cox published the first part of a major ‘Comparative Study of Infantile Autism and Specific Developmental Receptive Language Disorder’ in the British Journal of Psychiatry ( Rutter, Bartak and Cox, 1975 : 127–45). Rutter, Bartak and Cox’s studies found that, although there were similarities in these groups, comparisons showed that autistic children demonstrated particular ‘deviant’ forms of language such as echolalia, pronoun reversal, stereotyped utterances and metaphorical language. In the case of children who only had language disorders, such ‘deviant’ speech was not prevalent but this group was much more likely to have defects in articulation.

The language ‘deviance’ and impaired usage of spoken language and gesture seen in autistic children was different from the problems seen in other language-disordered children ( Rutter, Bartak and Cox, 1975 ; Bartak, Rutter and Cox,, 1977). Figure 3 shows a section from a table of items used to discriminate between these two groups in 1977 and the discriminant function which had been calculated from the 1975 study.

Section from table of items used in discriminant functions analyses ( Bartak, Rutter and Cox, 1977 ).

In 1970, the Journal of Autism and Childhood Schizophrenia had been established under the editorship of Leo Kanner with Rutter as associate editor representing Great Britain. The journal claimed to have no theoretical bias but simply the aspiration ‘to promote scientifically ascertained observations and facts from every source which can widen our horizon’ ( Kanner, 1971 : 14–19). The editors stated that the journal was ‘devoted to all psychoses and severe disorders of behaviour in childhood’ (ibid.). In 1979, the Journal of Autism and Childhood Schizophrenia was renamed the Journal of Autism and Developmental Disorders . Writing in the editorial of that year, Rutter, who had been promoted to European editor, along with Eric Schopler, who had replaced Kanner as chief editor in 1974, explained the transition as follows:

The title and scope of the journal have been broadened to include a wider range of developmental disorders related to autism. This carefully circumscribed broadening is also intended to clarify the developmental factors that shape the autistic symptom picture. ( Schopler, Rutter and Chess,1979 : 1)

It was clear that Rutter and Schopler had ambitions to build a new style of thinking about deviations in children’s development and that they saw the categories of ‘autism’ as central to this conceptual revolution. At the same time, they rigorously excluded the concepts of ‘psychosis’ and ‘schizophrenia’ from child psychology.

This was an important moment for child psychology because autism was such a central concept. Once this concept had been appropriated and defined as a developmental problem associated with language, the concept of hallucination, which had been a key concept in all descriptive psychopathology since the 19th century, was written out of developmental psychopathology. As autism was associated further with developmental disorders, hallucination was increasingly eradicated from the concept.

These changes were reflected in the publication of the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (1980). The category of ‘childhood schizophrenia’ was completely written out of DSM-III ( Volkmar, 2005 : 15). Instead, DSM-III introduced the category of ‘pervasive developmental disorders’, a diagnosis that included four sub-categories, namely ‘infantile autism’, ‘childhood onset pervasive developmental disorder’, ‘residual autism’ and an atypical form (J. C. Harris, 1998 : 184). At the same time, the older concept of autism, which had previously played an important part in the diagnostic criteria for adult schizophrenia in DSM-II , was completely removed from the diagnostic criteria for schizophrenia in adults and Robert Spitzer argued that this was due to its unreliability as an observable symptom ( Klerman et al. , 1984 ). In other words, autism was removed as a key concept in the diagnosis of adult schizophrenia and implemented as a category within pervasive developmental disorders of childhood.

DSM-III included a multi-axial model of diagnosis which the chair of the DSM task force, Robert Spitzer, claimed was to avoid the impression that it was a diagnostic bible and to further its use as a statistical manual ( Spitzer, 2001 ). Rutter was central to implementing the multi-axial system. In 1975, Rutter, David Shaffer and Michael Shepherd had published a report for the World Health Organisation which supported the development of a multi-axial system of diagnosis. The first model contained 3 axes, the first being the ‘clinical psychiatric syndrome’, the second the ‘intellectual level’ and the third listing ‘associated aetiological factors’. This multi-axial model was a development of Rutter’s work from the 1960s. His association with the World Health Organisation had broadened his profile and his multi-axial model was becoming well known in the field of psychiatry. After 1980, the DSM model of diagnosis in children’s psychiatric disorder became well established in the UK.

Autism as a neuro-cognitive/developmental disorder

In 1979, Lorna Wing and Judith Gould from the MRC Unit conducted a prevalence-study of what they termed ‘Severe Impairment of Social Interaction and Associated Abnormalities’ in children. They used the Camberwell Register, a sophisticated data-collection mechanism which had been established in 1964 by the Social Psychiatry Research Unit, to identify subjects (J. K. Wing and Hailey, 1972 ). At the time, Wing was establishing herself as a leading figure in autism research and her work later had major national and international influence. Wing and Gould argued that the ‘pattern of impairments and behaviour problems’ that they were describing had previously been ‘variously (and unfortunately) termed childhood psychosis , childhood autism , or childhood schizophrenia ’ and they argued that all of these conditions needed to be reconceptualized as problems of social impairment (L. Wing and Gould, 1979 : 11). Selection criteria drew from Rutter’s 3 key features of autism and were defined as: ‘absence or impairment of social interaction’, ‘absence or impairment of development of verbal or non-verbal language’, or ‘repetitive, stereotyped activities of any kind’. A total of 132 children was selected (L. Wing, Yeates et al. , 1976 ; L. Wing and Gould, 1979 ). Further assessments were given using the Children’s Handicaps, Behaviour and Skills (HBS) structured interview schedule which was a system of measurement developed by Wing and Gould to amalgamate both ‘psychotic’ and ‘retarded’ children, while at the same time enabling distinctions to be made according to their social abilities. The authors argued that this schedule was useful for distinguishing between autism and ‘the specific developmental receptive and expressive speech disorders’ (L. Wing and Gould, 1978 : 80–1).

By reintegrating the study of ‘retardation’ with the study of autism and then drawing new conceptual divisions between these two problems, Wing and Gould tried to create a new comprehensive framework for the study of problems of thinking in children. Figure 4 is a table showing distinctions between the two groups into which the sample was split – the ‘socially impaired’ and the ‘sociable severely retarded’. A further graph subdivided the ‘socially impaired’ group according to the severity of their impairment. ‘Aloof’ children were reported never to interact with others, ‘passive’ children allowed children to interact with them but showed little response and ‘odd’ children demonstrated bizarre forms of social interactions including ‘repetitive, idiosyncratic preoccupations’ in which they had no interest in the feelings of the other person involved. These distinctions were then correlated with associated organic conditions including Down’s Syndrome, deafness and visual impairments (L. Wing and Gould, 1979 ).

‘Comparison of socially impaired with sociable severely retarded’ (L. Wing and Gould, 1979 ).

Wing and Gould argued that their ‘system based on [the] severity of social impairment gave more statistically significant associations with behavioural, psychological and medical variables’ than previous systems of categorization and they questioned the usefulness of Kanner’s definition of infantile autism (L. Wing and Gould, 1979 : 25–7). They hypothesized that ‘certain areas or functions of the brain are responsible for the development of social interaction and symbolic imaginative activities’ and that these areas were affected in the children that they had described (ibid.: 26). Some organic pathologies such as Down’s Syndrome left these functions intact but destroyed others. They argued that ‘social impairment’ measures were the best way to conceptualize the mental problems of children because they were more closely related to known gross aetiology. Wing and Gould recommended that future studies of the mental problems of children based their divisions upon social impairment as measured by the HBS. ‘Impairments of reciprocal social interaction’ were reported to occur in 21.2 of every 10,000 children in the area studied, of whom 4.9 presented with a history of ‘typical autism’.

Wing and Gould’s attempt to place ‘autistic’ children on a continuum with other mentally abnormal children was similar to Anthony’s attempts to place ‘severely psychotic’ children on a continuum with other partially ‘psychotic’ children and they flagged up this connection (L. Wing and Gould, 1979 : 12). However, whereas Anthony's 3 criteria had been based on psychoanalytic and Piagetian styles of reasoning, Wing and Gould described the problem purely in behavioural terms creating their own triad of observable symptoms. In doing so, they helped to transform the problem of childhood psychosis and ego development into a problem of social behaviour and management. As Rutter's work has already distanced the concept of autism from hallucination and severe adult psychopathology, Wing then took the liberty to redefine all forms of psychopathology in infancy as forms of ‘social impairment’.

In 1981, Wing published a paper on ‘Asperger’s Syndrome: a Clinical Account’, in which she extended her argument that autism should be included within a ‘wider group of conditions which have, in common, impairment of development of social interaction, communication and imagination’ (L. Wing, 1981 ; Nadesan, 2005 ). She coined the term ‘Asperger's syndrome’ after reclaiming a 1944 article on autism by Hans Asperger. Although Asperger’s Syndrome was not included in the DSM until its 4th edition in 1994, Wing’s work in expanding the category of autism and linking it to other developmental disorders was highly influential and encouraged increasing numbers of studies which placed autism as the central problem through which to understand other forms of pathological or abnormal thought development in infants and children. These studies increasingly regarded autism as a problem of ‘social’ interaction, rather than a problem of emotional relationships with others. The ‘autism’ employed in these studies was not the ‘autism’ of schizophrenia, but neither was it Kanner's ‘autistic disturbance of affective contact’. It was instead the autism of ‘cognitive deficits’. The meaning of autism had been transformed and increasing numbers of children could now be defined by these new classificatory criteria.

Cognitive psychology: Lacking a ‘theory of mind’ and searching for ‘quasi-autism’

When Simon Baron-Cohen, Alan Leslie and Uta Frith argued that autistic children lacked a ‘theory of mind’ in 1985, they built on the post-1960s conception of autism, describing it as ‘a profound disorder in understanding and coping with the social environment’, in which the main symptom is ‘impairment in verbal and non-verbal communication’ ( Baron-Cohen, Leslie and Frith, 1985 ). Frith had conducted her PhD at the Institute of Psychiatry while Rutter and Wing were both there and she was greatly influenced by their approach. She had studied for her PhD under O’Connor and Hermelin on pattern detection in autistic children ( Bishop, 2006 ). Frith had argued that autistic children displayed an ‘input processing deficit’ which she later described as ‘weak central coherence’ ( Frith, 1970 , 2003 ). Frith, Cohen and Leslie took the term ‘theory of mind’ from the work of D. Premack and G. Woodruff who had employed it to describe the study of chimpanzees. They used it to describe the ability to attribute autonomous mental states to the self and others so as to predict and explain actions following. Leslie had been conducting work on the abilities of normal 2-year-olds to understand pretend play and argued that autistic children showed deficits in their capacity for imagination. Baron-Cohen, Leslie and Frith then put forward the hypothesis that autistic children suffered an impairment in the cognitive mechanism required for ‘mentalizing’ or representing mental states. ‘False belief’ tasks, in which subjects were tested to see if they could predict the thoughts of others, were employed to test this theory. In many trials, these tests were used to compare autistic children with control children that had low language abilities or low IQ levels ( Leslie and Frith, 1988 ; Perner et al. , 1989 ). These study designs were very similar to those used by Hermelin and O'Connor who had used ‘retarded’ or ‘mentally deficient’ children as controls. The description of autism as a ‘theory of mind’ deficit does not exclude subjects who may have good vocabulary, syntax, phonology and rote language. Their only failure relates to their ability to think of the mental states of others.

Baron-Cohen, Frith and Leslie drew from Piaget’s tests of ‘egocentricity’ in their proposition that autistic children lacked a ‘theory of mind’; however, they did not elaborate on the ways in which infants may perceive the minds and bodies of others. They had thus found a way to describe an individual’s relationship to other minds which completely bypassed the thought processes that may have mediated that relationship. This model was readily taken up by many British researchers because it represented exactly what was required in that historical moment – an account of the development of thought in infants which concerned their ability to relate to others, yet which did not speculate at all on the thought processes, hallucinatory or otherwise, that may have structured those relationships. This model had been imposed on researchers via the spread of epidemiological and statistical methodologies.

Although new models have been developed in Britain to conceptualize the mental problems of autistic children as ‘theory of mind’ deficits and ‘weak central coherence’, several pressing issues concerning the possible impact of early relationships on these functions have not gone away. The fact that autism researchers are still attempting to address some of the central questions raised in the 1940s discussions of autism and human relationships is most evident in Rutter et al. 's studies on Romanian orphans who had been seriously deprived during the early stages of their development. In 1999, Rutter and colleagues at the Institute of Psychiatry published a paper on the presentation of what they termed ‘quasi-autism’ in some of these children ( Rutter et al. , 1999 ). In 2007, Rutter drew from a larger sample to argue that around 1 in 10 of these severely deprived children showed ‘quasi-autism’ which was very similar to ‘ordinary autism’, although it differed to the extent that the children showed more unusual social approaches and unusual spontaneity in their communication. These children also showed some improvement between the ages of 4 and 6. All the children with ‘quasi-autism’ showed ‘theory of mind’ deficits, a finding which confirms the universality of that concept to cover general relational and social difficulties ( Rutter et al. , 2007 ). Furthermore, Romanian orphans adopted after 6 months were likely to show ‘theory of mind’ deficits even if they did not show full-blown quasi-autism ( Colvert, Rutter et al. , 2008 ). Interestingly, Rutter and colleagues have argued that infants who are severely deprived during the first 6 months of life do not develop ‘quasi-autism’, whereas those who were deprived for longer periods do have a tendency to do so. This finding perfectly revisits the controversial discussions between Melanie Klein and Anna Freud about the nature of thought during the first 6 months of life and whether infants during this phase were dominated by ‘primary narcissism’ as Anna Freud had argued. Of course, Rutter does not discuss these issues in relation to fantasy and hallucination. However, he does accept that environmental circumstances can affect the development of ‘quasi-autism’, a finding which is less contentious when phrased in new language.

The influence of human relationships on thought will always be a subject of interest to child psychologists but the way in which these issues are currently discussed has been fundamentally shaped by the radical transformation of the concept of autism in the middle of the 20th century. Statistical methodologies and epidemiological studies have ushered in an entirely new way to think about human relationships which have become increasingly dominant. This model of describing children’s mental abnormalities has grown together with increases in rates of autism since the 1990s.

There are some researchers who have challenged this general shift in the meaning of autism although they have been rare, and are becoming increasingly so. For example, Peter Hobson, a psychoanalyst and psychiatrist based jointly at the Tavistock Clinic and University College London, has argued that ‘theory of mind’ deficits are merely secondary phenomena to the primary problem which is the infant’s inability to emotionally engage with others ( Hobson, 1993 , 2002 ). However, even Hobson's complex description of psychological development in autistic children rarely employs the language of hallucination and fantasy in relation to schizophrenia. Recently, in the USA, Judith Rapoport and colleagues at the National Institutes of Health have started to ‘revisit’ the link previously drawn between autism and childhood schizophrenia, arguing that autism and other developmental disorders may be a risk-factor for schizophrenia (Rapoport, Chavez et al. , 2009). If schizophrenia and autism are linked in the future through genetic studies, there may be another shift in the description of infantile thought. Whether this would change the descriptive methods that have now become entrenched around autism following psychiatric epidemiology, and whether it could again implicate hallucinations in infants and children is yet to be seen.

This article has focused on the origins and foundations of autism as a concept in Britain. Up until the 1950s, the concepts of childhood schizophrenia and autism were used to reframe central issues in child development based on the idea of infantile hallucination. However, in the 1960s, the expansion of the epidemiological method in child psychiatry and developmental psychology led to new standardized measures of sensory-motor function and language ability. A child’s behavioural and linguistic ‘stereotypies’ could be correlated with similar ‘stereotypies’ in other children through cohort studies. These studies gave rise to new scientific facts about infantile psychology. Lotter’s 24 behavioural items for autism were developed to enable reproducible studies which would not be affected by the subjective judgements of individual researchers. It was in response to these changes that statistical researchers such as Lotter and Rutter transformed the meaning of autism from ‘a withdrawal into fantasy’, as in the Piagetian description of the concept, to an inability to fantasize which could be calculated through a sum of cognitive measures.

The claim that statistical inference should be used as the basis of scientific knowledge is, of course, not an invention of autism researchers in the 1960s. Such a claim can be traced back to the work of Karl Pearson, Francis Galton and Cyril Burt, and Ronald Fisher and Austin Bradford-Hill developed the statistical method in scientific medical research. However, autism researchers used epidemiological studies in order to answer wider questions about the development of all infantile thought. Autism has always referred to the most severe pathology in infantile thought and changes in its meaning reflect broader historical changes in what is considered abnormal in the thought and behaviour of all infants and children. These central abnormalities are now framed by new language concerning cognitive abilities and deficits which were not considered relevant when autism was related purely to psychopathology rather than learning disabilities as well. The fact that researchers still hold on to autism as a key term is reflected in Rutter's studies of severely deprived children which employ the concept of ‘quasi-autism’ to explain the possible outcome of social deprivation in all infants (e.g. Rutter, 1998 ; Rutter, Krepner and O’Connor, 2001).

The most significant development following the introduction of statistical and epidemiological methods in child psychiatry has been the expansion of behavioural, communicative and cognitive categories and the virtual disappearance of the concepts of child hallucination and fantasy. Autism was thereby disassociated from the key concept of descriptive psychopathology – hallucination. Perhaps these are simply more enlightened times in which researchers no longer speculate wildly about the thoughts of infants but collect statistical evidence instead. This has nothing to do with the question of whether psychologists blame parents for infant psychopathology, but rather whether or not psychologists take the liberty to enter the internal mental life of infants. The spread of epidemiology and statistical methodologies in child psychiatry have consequences which spread far wider than the study of just autism. They have entered into all descriptions and studies of infants and children who display mental atypicalities. ‘Autism’ is a defining concept and changes in its meaning have altered wider perceptions of how infants and children think.

Author biography

Bonnie Evans is a Wellcome Trust postdoctoral research fellow at King’s College, London, Centre for Humanities and Health. Her 2010 PhD thesis (Department of History and Philosophy of Science, Cambridge University) examined the origins of child psychiatry and childhood schizophrenia research and its influence on contemporary theories of autism in Britain and was awarded a prize from the International Society for the History of the Neurosciences. She is currently conducting further research on the history of psychiatric treatment and research at the Maudsley Hospital, London, and on the history of child psychiatry and autism. She is also working on a collaborative book on ‘The Brain and the Mind’ with Lisa Appignanesi and Lara Feigel.

1. On Bleuler’s use of the terms ‘autistic’ and ‘dereistic’ see Shorter (2005) .

2. National Archives, London. ED50/994. Special Educational Treatment Psychotic Autistic Children 1961–1965.

Primary Sources

What is autism spectrum disorder? How to support the community this Autism Acceptance Month

April marks Autism Acceptance Month with World Autism Day occurring on April 2 every year. The month is meant to be a time for uplifting autistic voices and sharing in the community's joy. But for Samantha Edwards, an autistic content creator and neurodivergent life coach, the month also signifies an influx of harmful myths about autistic people. 

"April is a wonderful month to crack down on that and listen to autistic voices and their stories and listen to their struggles," she says. "Acceptance, at the end of the day, is going to promote more inclusivity."

Here’s how you can uplift the neurodivergent community this April and all year long.

​​​What is autism? 

Autism is a developmental disability that affects the way people experience the world . This may include differences in processing senses, thinking, physically moving, communicating, socializing and going about daily living. 

“We’re born autistic and we’re autistic our whole lives,” says Zoe Gross, the director of advocacy at Autistic Self Advocacy Network . “It affects everything about the way we interact with and perceive the world.”

Autism affects every autistic person differently, and there isn’t one way to be autistic. Gross describes it as an ice cream sundae bar: The traits of autism can be mixed and matched from person to person. 

Here’s what autism isn’t, Gross says – something to be scared of or pity.

“In truth, autism is just a neutral fact about us, it’s not necessarily a good or a bad thing,” she says. “It’s just the way our brains are.”

Another misconception is that autistic people don’t have empathy. Gross recalled a time when a teacher asked her if she loved her parents. Of course she loves them, she responded, but the question itself was a symptom of a larger myth about autistic people and emotions. 

“Where that comes from is that we may not know what other people are feeling if they don’t tell us because autistic people may not be good at reading body language or other kinds of subtle social cues,” Gross says. “But that doesn’t mean we don’t care what people are feeling.”

World Autism Day: A love letter to parents of a newly-diagnosed child

How common is autism? 

About one in 36 children have autism spectrum disorder, the Centers for Disease Control and Prevention states. This number is on the rise, especially as children of color receive more diagnoses after being largely overlooked throughout history. 

Edwards started her online autism advocacy journey to combat the misconceptions about autism. As an autistic person and a parent of two autistic children, she says she wants to make the world a more accessible place for future generations. 

A large part of her work is advocating for the self-diagnosed community, which she says “are very welcome and included in the autistic community.”

One of the more harmful narratives is that people, especially teenagers, are self-diagnosing after watching a handful of TikTok videos with captions like “Signs you may be autistic” or “10 things that are actually traits of autism.” But that’s “really not the case,” says Edwards. Online platforms like TikTok give the autistic community, like other marginalized communities, more visibility than ever before. 

“It is harmful for all of these self-diagnosed autistics that really did put in the research – some have years, even a lifetime of research – to be told, ‘Oh, you watched a couple TikTok videos so you’re not valid,'” Edwards says. 

Some medical professionals push back against self-diagnosing, especially when it comes to social media. But there’s also the nuanced issue of access to healthcare services that may lead to a professional diagnosis, which can be limited for some autistic individuals . 

What is Autism Acceptance Month?

April is Autism Acceptance Month but many, especially those outside of the autism community, used to refer to the month as " Autism Awareness Month." Autistic advocacy organizations have been using “acceptance” rather than “awareness” for over a decade, and the Autism Society of America shifted the terminology in 2021.

According to ASAN, Autism Acceptance Month was created by and for autistic people to respect the rights and humanity of all autistic people and center “the perspectives and needs of autistic people with intellectual disabilities, nonspeaking autistic people, and autistic people with the highest support needs.”

Using “acceptance” instead of “awareness” is an intentional choice because, as Edwards says, “we’re just moving on.”

“It’s 2023, I do believe most people are aware of what autism is,” she says. “We’ve got the awareness and now we need the resources, we need the advocacy.”

Awareness campaigns have historically focused on how many people have autism or a search for a “cure.” A now-removed  2009 campaign  from advocacy organization Autism Speaks opened by saying “I am autism. I’m visible in your children, but if I can help it, I am invisible to you until it’s too late.”

The “awareness” approach, Gross says, further stigmatizes autism as something scary.

“That’s not the way we want to approach giving people information about autism, we want people to view autism as a part of human diversity and autistic people as part of their community,” Gross says. 

How to support the autistic community

Don’t speak over autistic voices

“ Nothing about us without us ” is a disability rights slogan that’s top of mind during Autism Acceptance Month. 

When it comes to research, policy and advocacy, the most important thing is that autistic people are “in the driver’s seat,” Gross says. It means that decisions about autism need to be made by or with autistic people. It also means centering the stories and experiences of autistic people.

Avoid harmful labels and language

“Low-functioning” and “high-functioning” are labels often ascribed to autistic people. These are harmful ,  ASAN says, because “we all have things we are good at and things we need help with.”

“People will say, ‘How can I do without the terms low-functioning and high-functioning?’ And what I want to ask is like ‘What are you doing with them now?’” Gross says. “What I encourage people to do is just say what they mean. If they mean this person can’t speak, (say) ‘I’m talking about someone who can’t speak.’ If they mean this person has a job, just say ‘I’m talking about an autistic person who has a job.’”

Neurotypical people may also wonder what’s more appropriate to say – person with autism or autistic person? 

Many self-advocates prefer identity first language  because it works against the stigma that being autistic is something bad or something that makes you less than. Identity first language (“autistic person”) recognizes and validates that identity. 

“Autism is something that you are and not something that you have, you’re not carrying autism around in a bag,” Edwards says. “It’s something that makes your brain different.” 

But it’s a personal preference . For example, Gross says people with intellectual disabilities may use person-first language ("person with autism") because “they feel they’ve been so dehumanized and people only see their disability and don’t see them.” 

The bottom line: How someone refers to their autism is personal based on what makes them feel the most affirmed and validated.  

Support autistic-run organizations and businesses

Edwards recommends supporting organizations that center autistic voices and are run by autistic people, like ASAN and the Autistic Women and Nonbinary Network.

This month, Edwards says she’ll be using her platform to uplift other autistic and disabled creators.

“There’s so many of us that are … trying to make a really big difference in this movement, so I’m really proud of everyone this past year,” she says. “I just want to uplift each other and get the right message out.”

Organizations with primarily neurotypical leadership have led autistic advocates to move away from their symbols  (like Autism Speaks’ signature blue color and puzzle piece) in favor of new ones created by autistic self-advocates. The first puzzle piece logo in 1963 featured a crying child in the center and was designed to show autism as a “puzzling condition.” A 2018 study found the general public has a negative implicit bias against the imagery of a puzzle piece, which participants associated with “imperfection, incompletion, uncertainty, difficulty, the state of being unsolved, and, most poignantly, being missing.”

“We recognize discord within the community, including those who dislike the puzzle piece symbol or prefer a different symbol, but there are also many who embrace it and want to continue to see it associated with autism,” Autism Speaks told USA TODAY in a statement.

The organization says it is regularly seeking feedback from those within the autistic community on whether or not to continue its use and encouraged feedback at [email protected] .

Many favor a rainbow or gold infinity symbol and use “ Red Instead ,” which Edwards says symbolizes the passion autistic people have. 

Don’t perpetuate myths about autism 

Edwards recommends neurotypical people support the neurodiverse community by staying up to date on  current research  and taking a second glance before sharing something that furthers stereotypes about autistic people. 

“We all deserve our human rights, and we all deserve respect,” Gross says. “We all deserve to be able to make choices in our lives, we deserve to live free from neglect and abuse, we deserve to have services that are truly person-centered and individualized for us and that meet our needs. Those aren’t optional, fancy things that you get by being mildly impacted.”

• Clinical Research
• Interventional
• Radiation Oncology
• Women's
• Artificial Intelligence
• Enterprise Imaging
• Imaging Informatics
• Informatics
• Compensation
• Education & Training
• Patient Care
• Policy & Regulations
• Practice Management
• Professional Associations
• Experience Stories
• Webinars & Videos

Search form

Experts are inching closer to being able to objectively understand how the brains of individuals with autism spectrum disorder (ASD) function differently from their neurotypical peers. 

New research from the University of Virginia suggests that the microstructures of the brains of those with autism differ from those not considered on the spectrum. This, experts involved in the study explained, offers further insight into exactly what is happening inside the brain that causes individuals on the spectrum to process information differently. 

Scientists used a special type of MRI exam— diffusion tensor imaging —to analyze the water that continuously moves throughout the brain and cell membranes, while paying close attention to the myelin and axons. Through this, researchers were able to calculate individuals’ axonal conduction velocity, which offers insight into an axon’s ability to transfer information throughout the brain. 

When comparing the imaging of people on the spectrum to others who are otherwise considered neurotypical, the team found significant differences in the extracellular water and conduction velocity throughout the cortex, subcortex and white matter skeleton between the two groups, with the ASD group showing increased water presence and decreased conduction velocity. 

The group used these metrics to create mathematical models of the brains’ microstructures, which, in turn, allowed them to identify notable structural differences between the two groups. The participants’ scores on the Social Communication Questionnaire—a tool commonly used when diagnosing ASD —were found to be directly related to the microstructural differences observed on imaging. 

“What we're seeing is that there's a difference in the diameter of the microstructural components in the brains of autistic people that can cause them to conduct electricity slower,” lead author of the paper, Benjamin Newman, a postdoctoral researcher with UVA’s Department of Psychology, said in a release . “It's the structure that constrains how the function of the brain works.”  

Co-author John Darrell Van Horn, a professor of psychology and data science at UVA, highlighted the objective nature of the study, pointing out that ASD is typically diagnosed based on a pattern of behaviors, which can be quite subjective depending on who is conducting the examination. 

“We need greater fidelity in terms of the physiological metrics that we have so that we can better understand where those behaviors come from,” Van Horn said. “This is the first time this kind of metric has been applied in a clinical population, and it sheds some interesting light on the origins of ASD.” 

The authors suggested that this research could lay the foundation for identifying biological targets on which experts could focus future treatments and therapies, providing an objective means of measuring effectiveness. 

AI able to identify autism in children with 98.5% accuracy

Mri scans link atypical growth of key brain structure during infancy with autism, findings potentially linked to autism spotted on routine prenatal ultrasound, research shows, 6 tips for making mri exams more autism-friendly.

1.  Benjamin T. Newman, Zachary Jacokes, Siva Venkadesh, Sara J. Webb, Natalia M. Kleinhans, et al. "Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder," PLOS ONE, 2024

In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She joined Innovate Healthcare in 2021 and has since put her unique expertise to use in her editorial role with Health Imaging.

Related Content