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Proposed causes of autism

Many causes of autism, including environmental and genetic factors, have been recognized or proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD (autism spectrum disorder) is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction, as well as restricted and repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals. There are many known environmental, genetic, and biological causes of autism. Research indicates that genetic factors are predominate in the appearance of autism; however, the heritability of autism is complex, and many of the genetic interactions involved are unknown. Many other causes have been proposed. Different underlying brain dysfunctions have been hypothesized to result in the common symptoms of autism, just as completely different brain types result in intellectual disability. In recent years, the prevalence and number of people diagnosed with the disorder have increased dramatically. There are many potential reasons for this occurrence, particularly the changes in the diagnostic criteria for autism. Environmental factors that have been claimed to contribute to autism or exacerbate its symptoms, or that may be important to consider in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, and illicit drugs. However, there is overwhelming scientific evidence showing that there is no causal association between the measles mumps rubella (MMR) vaccine and autism. Although there is no definitive evidence that the vaccine preservative thimerosal causes autism, studies have indicated a possible link between thimerosal and autism in individuals with a hereditary predisposition for autoimmune disorders. In 2007, the Center for Disease Control stated there was no support for a link between thimerosal and autism, citing evidence from several studies, as well as a continued increase in autism cases following the removal of thimerosal from childhood vaccines.

Genetic factors may be the most significant cause of autism. Early studies of twins had estimated heritability to be over 90%, meaning that genetics explains over 90% of whether a child will develop autism. Evidence so far still suggests a strong genetic component, with one of the largest and most recent studies estimating the heritability at 83%. Many of the non autistic co twins had learning or social disabilities. For adult siblings the risk for having one or more features of the broader autism phenotype might be as high as 30%. In spite of the strong heritability, most cases of autism occur sporadically with no recent evidence of family history. It has been hypothesized that spontaneous de novo mutations in the sperm or egg contribute to the likelihood of developing autism. The first genes to be definitively shown to contribute to risk for autism were found in the early 1990s by researchers looking at gender specific forms of autism caused by mutations on the X chromosome. An expansion of the CGG trinucleotide repeat in the promoter of the gene FMR1 in boys causes fragile X syndrome, and at least 20% of boys with this mutation have behaviors consistent with autism spectrum disorder. Mutations that inactivate the gene MECP2 cause Rett syndrome, which is associated with autistic behaviors in girls, and in boys the mutation is embryonic lethal. Besides these early examples, the role of de novo mutations in autism first became evident when DNA microarray technologies reached sufficient resolution to allow the detection of copy number variation (CNV) in the human genome. CNVs are the most common type of structural variation in the genome, consisting of deletions and duplications of DNA that range in size from a kilobase to a few megabases. Microarray analysis has shown that de novo CNVs occur at a significantly higher rate in sporadic cases of autism as compared to the rate in their typically developing siblings and unrelated controls. A series of studies have shown that gene disrupting de novo CNVs occur approximately four times more frequently in autism than in controls and contribute to approximately 5–10% of cases. Based on these studies, there are predicted to be 130–234 autism related CNV loci. However, structural variants in individuals with autism are much larger and four times more likely to disrupt genes, mirroring findings from CNV studies. There are predicted to be 350 450 genes that significantly increase susceptibility to autism when impacted by inactivating de novo mutations. A further 12% of cases are predicted to be caused by protein altering missense mutations that change an amino acid but do not inactivate a gene. The Simons Foundation Autism Research Initiative (SFARI) details the evidence for each genetic locus associated with autism. These early gene and CNV findings have shown that the cognitive and behavioral features associated with each of the underlying mutations is variable. Each mutation is itself associated with a variety of clinical diagnoses, and can also be found in a small percentage of individuals with no clinical diagnosis. Thus the genetic disorders that comprise autism are not autism specific. The mutations themselves are characterized by considerable variability in clinical outcome and typically only a subset of mutation carriers meet criteria for autism. This variable expressivity results in different individuals with the same mutation varying considerably in the severity of their observed particular trait. The conclusion of these recent studies of de novo mutation is that the spectrum of autism is breaking up into quanta of individual disorders defined by genetics. Mutations in this gene act in a dominant fashion. Mutations in this gene appear to cause hyperconnectivity between the neurons. A study conducted on 42,607 autism cases has identified 60 new genes, five of which had a more moderate impact on autistic symptoms. The related gene variants were often inherited from the participant's parents.

Epigenetic mechanisms may increase the risk of autism. Epigenetic changes occur as a result not of DNA sequence changes but of chromosomal histone modification or modification of the DNA bases. Such modifications are known to be affected by environmental factors, including nutrition, drugs, and mental stress. Interest has been expressed in imprinted regions on chromosomes 15q and 7q. Most data supports a polygenic, epistatic model, meaning that the disorder is caused by two or more genes and that those genes are interacting in a complex manner. Several genes, between two and fifteen in number, have been identified and could potentially contribute to disease susceptibility. However, an exact determination of the cause of ASD has yet to be discovered and there probably is not one single genetic cause of any particular set of disorders, leading many researchers to believe that epigenetic mechanisms, such as genomic imprinting or epimutations, may play a major role. Epigenetic mechanisms can contribute to disease phenotypes. Epigenetic modifications include DNA cytosine methylation and post translational modifications to histones. These mechanisms contribute to regulating gene expression without changing the sequence of the DNA and may be influenced by exposure to environmental factors and may be heritable from parents. Genomic imprinting may also contribute to the development of autism. Genomic imprinting is another example of epigenetic regulation of gene expression. In this instance, the epigenetic modification(s) causes the offspring to express the maternal copy of a gene or the paternal copy of a gene, but not both. The imprinted gene is silenced through epigenetic mechanisms. Candidate genes and susceptibility alleles for autism are identified using a combination of techniques, including genome wide and targeted analyses of allele sharing in sib pairs, using association studies and transmission disequilibrium testing (TDT) of functional and/or positional candidate genes and examination of novel and recurrent cytogenetic aberrations. Results from numerous studies have identified several genomic regions known to be subject to imprinting, candidate genes, and gene environment interactions. Particularly, chromosomes 15q and 7q appear to be epigenetic hotspots in contributing to autism. Also, genes on the X chromosome may play an important role, as in Rett Syndrome.

The development of autism is associated with several prenatal risk factors, including advanced age in either parent, diabetes, bleeding, and maternal use of antibiotics and psychiatric drugs during pregnancy. Autism has been linked to birth defect agents acting during the first eight weeks from conception, though these cases are rare. If the mother of the child is dealing with autoimmune conditions or disorders while pregnant, it may have an effect on the child's development of autism. All of these factors can cause inflammation or impair immune signaling in one way or another. Likewise, these are all known risk factors for sleep apnea. One study found that gestational sleep apnea was associated with low reading test scores in children and that this effect may be mediated by an increased risk of the child having sleep apnea themselves. Another study reported low social development scores in 64% of infants born to mothers with sleep apnea compared to 25% of infants born to controls, suggesting sleep apnea in pregnancy may have an effect on offspring neurodevelopment. There was also an increase in the amount of snoring the mothers with sleep apnea reported in their infants when compared to controls. One study found significant improvements in ADHD like symptoms, aggression, social problems and thought problems in autistic children who underwent adenotonsillectomy for sleep apnea. Sleep problems in autism have been linked in a study to brain changes, particularly in the hippocampus, though this study does not prove causation. A common presentation of sleep apnea in children with autism is insomnia.

Prenatal viral infection has been called the principal non genetic cause of autism. Prenatal exposure to rubella or cytomegalovirus activates the mother's immune response and may greatly increase the risk for autism in mice. Congenital rubella syndrome is the most convincing environmental cause of autism. Infection associated immunological events in early pregnancy may affect neural development more than infections in late pregnancy, not only for autism, but also for psychiatric disorders of presumed neurodevelopmental origin, notably schizophrenia.

Teratogens are environmental agents that cause birth defects. Some agents that are theorized to cause birth defects have also been suggested as potential autism risk factors, although there is little to no scientific evidence to back such claims. These include exposure of the embryo to valproic acid, thalidomide or misoprostol. These cases are rare. Questions have also been raised whether ethanol (grain alcohol) increases autism risk, as part of fetal alcohol syndrome or alcohol related birth defects.

Maternal inflammatory and autoimmune diseases can damage embryonic and fetal tissues, aggravating a genetic problem or damaging the nervous system.

Thyroid problems that lead to thyroxine deficiency in the mother in weeks 8–12 of pregnancy have been postulated to produce changes in the fetal brain leading to autism. Thyroxine deficiencies can be caused by inadequate iodine in the diet, and by environmental agents that interfere with iodine uptake or act against thyroid hormones. Possible environmental agents include flavonoids in food, tobacco smoke, and most herbicides. This hypothesis has not been tested. Diabetes in the mother during pregnancy is a significant risk factor for autism; a 2009 meta analysis found that gestational diabetes was associated with a twofold increased risk. A 2014 review also found that maternal diabetes was significantly associated with an increased risk of autism. Although diabetes causes metabolic and hormonal abnormalities and oxidative stress, no biological mechanism is known for the association between gestational diabetes and autism risk. Maternal diagnoses of polycystic ovary syndrome was found to associated with higher risk of autism. Maternal obesity during pregnancy may also increase the risk of autism, although further study is needed. Maternal malnutrition during preconception and pregnancy influences fetal neurodevelopment. Intrauterine growth restriction is associated with autism, in both term and preterm infants.

It has been hypothesized that folic acid taken during pregnancy could play a role in reducing cases of autism by modulating gene expression through an epigenetic mechanism. This hypothesis is supported by multiple studies. Prenatal stress, consisting of exposure to life events or environmental factors that distress an expectant mother, has been hypothesized to contribute to autism, possibly as part of a gene environment interaction. Autism has been reported to be associated with prenatal stress both with retrospective studies that examined stressors such as job loss and family discord, and with natural experiments involving prenatal exposure to storms; animal studies have reported that prenatal stress can disrupt brain development and produce behaviors resembling symptoms of autism. However, other studies have cast doubts on this association, notably population based studies in England and Sweden finding no link between stressful life events and autism. The fetal testosterone theory hypothesizes that higher levels of testosterone in the amniotic fluid of mothers pushes brain development towards improved ability to see patterns and analyze complex systems while diminishing communication and empathy, emphasizing "male" traits over "female", or in E S theory terminology, emphasizing "systemizing" over "empathizing". One project has published several reports suggesting that high levels of fetal testosterone could produce behaviors relevant to those seen in autism. Based in part on animal studies, diagnostic ultrasounds administered during pregnancy have been hypothesized to increase the child's risk of autism. This hypothesis is not supported by independently published research, and examination of children whose mothers received an ultrasound has failed to find evidence of harmful effects. Some research suggests that maternal exposure to selective serotonin reuptake inhibitors during pregnancy is associated with an increased risk of autism, but it remains unclear whether there is a causal link between the two. There is evidence, for example, that this association may be an artifact of confounding by maternal mental illness.

Autism is associated with some perinatal and obstetric conditions. Infants that are born pre term often have various neurodevelopmental impairments related to motor skills, cognition, receptive and expressive language, and socio emotional capabilities. Pre term infants are also at a higher risk of having various neurodevelopmental disorders such as cerebral palsy and autism, as well as psychiatric disorders related to attention, anxiety, and impaired social communication. There is growing evidence that perinatal exposure to air pollution may be a risk factor for autism, although this evidence has methodological limitations, including a small number of studies and failure to control for potential confounding factors. A few studies have found an association between autism and frequent use of acetaminophen (e. g. Tylenol, Paracetamol) by the mother during pregnancy. This association does not necessarily demonstrate a causal relationship.

A wide variety of postnatal contributors to autism have been proposed, including gastrointestinal or immune system abnormalities, allergies, and exposure of children to drugs, infection, certain foods, or heavy metals. The evidence for these risk factors is anecdotal and has not been confirmed by reliable studies.

Paracetamol (acetaminophen) has been suggested as a possible risk factor for autism and other neurodevelopmental disorders. A study has found that male children exposed to Paracetamol before the age of 2 years old are associated with being at risk for being diagnosed with autism. However, a large prospective review of 2,480,797 children published in JAMA Pediatrics in April 2024 found "acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis".

This theory hypothesizes that an early developmental failure involving the amygdala cascades on the development of cortical areas that mediate social perception in the visual domain. The fusiform face area of the ventral stream is implicated. The idea is that it is involved in social knowledge and social cognition, and that the deficits in this network are instrumental in causing autism.

This theory hypothesizes that autoantibodies that target the brain or elements of brain metabolism may cause or exacerbate autism. It is related to the maternal infection theory, except that it postulates that the effect is caused by the individual's own antibodies, possibly due to an environmental trigger after birth. It is also related to several other hypothesized causes; for example, viral infection has been hypothesized to cause autism via an autoimmune mechanism. Interactions between the immune system and the nervous system begin early during embryogenesis, and successful neurodevelopment depends on a balanced immune response. It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of autism. A small percentage of autism cases are associated with infection, usually before birth. Results from immune studies have been contradictory. Some abnormalities have been found in specific subgroups, and some of these have been replicated. It is not known whether these abnormalities are relevant to the pathology of autism, for example, by infection or autoimmunity, or whether they are secondary to the disease processes. As autoantibodies are found in diseases other than autism, and are not always present in autism, the relationship between immune disturbances and autism remains unclear and controversial. A 2015 systematic review and meta analysis found that children with a family history of autoimmune diseases were at a greater risk of autism compared to children without such a history. When an underlying maternal autoimmune disease is present, antibodies circulating to the fetus could contribute to the development of autism spectrum disorders.

Gastrointestinal problems are one of the most commonly associated medical disorders in people with autism. These are linked to greater social impairment, irritability, behavior and sleep problems, language impairments and mood changes, so the theory that they are an overlap syndrome has been postulated. Studies indicate that gastrointestinal inflammation, food allergies, gluten related disorders (celiac disease, wheat allergy, non celiac gluten sensitivity), visceral hypersensitivity, dysautonomia and gastroesophageal reflux are the mechanisms that possibly link both. A 2018 review suggests that the frequent association of gastrointestinal disorders and autism is due to abnormalities of the gut–brain axis. It is based on the idea that defects in the intestinal barrier produce an excessive increase in intestinal permeability, allowing substances present in the intestine (including bacteria, environmental toxins, and food antigens) to pass into the blood. The data supporting this theory are limited and contradictory, since both increased intestinal permeability and normal permeability have been documented in people with autism. Studies with mice provide some support to this theory and suggest the importance of intestinal flora, demonstrating that the normalization of the intestinal barrier was associated with an improvement in some of the autism like behaviors. This allows passage of bacterial endotoxins from the gut into the bloodstream, stimulating liver cells to secrete tumor necrosis factor alpha (TNFα), which modulates blood–brain barrier permeability. Studies on ASD people showed that TNFα cascades produce proinflammatory cytokines, leading to peripheral inflammation and activation of microglia in the brain, which indicates neuroinflammation. Later studies found secretin clearly ineffective in treating autism.

In 1979, a possible association between autism and opiate was proposed, it was noted that injecting small amounts of opiates into young laboratory animals resulted in symptoms similar to those seen in autistic children. The possibility of a relationship between autism and the consumption of gluten and casein was first articulated by Kalle Reichelt in 1991. Opiate theory hypothesizes that autism is the result of a metabolic disorder in which opioid peptides gliadorphin (aka gluteomorphin) and Casomorphin, produced through metabolism of gluten (present in wheat and related cereals) and casein (present in dairy products), pass through an abnormally permeable intestinal wall and then proceed to exert an effect on neurotransmission through binding with opioid receptors. It has been postulated that the resulting excess of opioids affects brain maturation and causes autistic symptoms including: behavioral difficulties, attention problems, and alterations in communicative capacity and social and cognitive functioning. Although high levels of these opioids are eliminated in the urine, it has been suggested that a small part of them cross into the brain causing interference of signal transmission and disruption of normal activity. Three studies have reported that urine samples of people with autism show an increased 24 hour peptide excretion. As of 2021, reliable studies have not demonstrated the benefit of gluten free diets in the treatment of autism. Although there have been many studies on the role of vitamin D in the development of autism, the majority of them are limited by their inability to assess the deficiency prior to an autism diagnosis.

Multiple studies have made attempts to study the relationship between toxic exposure and autism. However, these studies often met with limitations related to the measurement of toxic exposure the methods for which were often indirect and cross sectional. Systematic reviews have been conducted for numerous toxins including air pollution, thimerosal, inorganic mercury, and levels of heavy metals in hair, nails, and bodily fluids. Significant evidence has not been found of an association between autism and the concentration of mercury, copper, cadmium, selenium, and chromium in the hair, nails, and bodily fluids.

This theory hypothesizes that autistic behaviors depend at least in part on a developmental dysregulation that results in impaired function of the locus coeruleus–noradrenergic (LC NA) system. The LC NA system is heavily involved in arousal and attention; for example, it is related to the brain's acquisition and use of environmental cues.

Oxidative stress, oxidative DNA damage and disruptions of DNA repair have been postulated to play a role in the etiopathology of both ASD and schizophrenia. Physiological factors and mechanisms influence by oxidative stress are believed to be highly influential to autism risk. Interactions between environmental and genetic factors may increase oxidative stress in children with autism. This theory hypothesizes that toxicity and oxidative stress may cause autism in some cases. Evidence includes genetic effects on metabolic pathways, reduced antioxidant capacity, enzyme changes, and enhanced biomarkers for oxidative stress. Polymorphism of genes involved metabolization of glutathione is evidenced by lower levels of total glutathione, and higher levels of oxidized glutathione in autistic children. Based on this theory, antioxidants may be a useful treatment for autism. Environmental factors can influence oxidative stress pre, peri, and postnatally and include heavy metals, infection, certain drugs, and toxic exposure from various sources including cigarette smoke, air pollutants, and organophosphate pesticides. It has been theorized that perceptions towards the characteristics of autistic individuals have been heavily influenced by neurotypical ideologies and social norms. Mild and moderate variations of autism are particular targets of the theory that social factors determine what it means to be autistic. The theory hypothesizes that individuals with these diagnoses inhabit the identities that have been ascribed to them, and promote their sense of well being by resisting or appropriating autistic ascriptions. Lynn Waterhouse suggests that autism has been reified, in that social processes have endowed it with more reality than is justified by the scientific evidence. Although social construction of the autistic identity can have a positive impact on the well being and treatment of autistic individuals. Autism and autistic traits are typically associated with the masculine identity. This association severely limits autistic women's ability to benefit from the freedom men might attain through the appropriation of the social constructed autistic identity. Autism diagnoses are typically associated with individuals who identify as 'White.' Because of this, individual from other racial and ethnic backgrounds are often overlooked, misdiagnosed, and underrepresented in relevant studies. It has been suggested that these trait advantages may have resulted from the exchange of socially beneficial traits with ones that promote technological skills and systematic thought processes. In future studies, autism may the shown to be similar to diseases, such as sickle cell anemia, that demonstrate balanced polymorphism. A 2011 study proposed the "Solitary Forager Hypothesis" in which autistic traits, including increased abilities for spatial intelligence, concentration and memory, could have been naturally selected to enable self sufficient foraging in a more solitary environment. However, the author notes that such individuals likely foraged by themselves while occasionally interacting with intimate people or groups. A study conducted by Spikins et al. (2016) examined the role of Asperger syndrome as "an alternative pro social adaptive strategy", which may have developed as a result of the emergence of "collaborative morality" in the context of small scale hunter gathering. The authors further suggest that "mutual interdependence of different social strategies" may have "contributed to the rise of innovation and large scale social networks".

One theory on the evolutionary and biological origins of autism traits in Homo sapiens that has gained recent attention in the 2010s and 2020s is that some genes linked to autism may have originated from early humans crossbreeding with Neanderthals, an extinct group of archaic humans (generally regarded as a distinct species, Homo neanderthalensis, though some regard it as a subspecies of Homo sapiens, referred to as H. sapiens neanderthalensis) who lived in Eurasia until about 40,000 years ago. A possible link between autism spectrum disorders (ASDs) and Neanderthal DNA was identified in 2009, pending genome sequencing. The first Neanderthal genome sequence was published in 2010, and strongly indicated interbreeding between Neanderthals and early modern humans. The genomes of all studied modern populations contain Neanderthal DNA. or 1.8–2.4% in modern Europeans and 2.3–2.6% in modern East Asians. Pre agricultural Europeans appear to have had similar, or slightly higher, Such low percentages of Neanderthal DNA in all present day populations indicate infrequent past interbreeding, unless interbreeding was more common with a different population of modern humans which did not contribute to the present day gene pool. Of the inherited Neanderthal genome, 25% in modern Europeans and 32% in modern East Asians may be related to viral immunity. In all, approximately 20% of the Neanderthal genome appears to have survived in the modern human gene pool. However, due to their small population and resulting reduced effectivity of natural selection, Neanderthals accumulated several weakly harmful mutations, which were introduced to and slowly selected out of the much larger modern human population; the initial hybridised population may have experienced up to a 94% reduction in fitness compared to contemporary humans. By this measure, Neanderthals may have substantially increased in fitness. A 2017 study focusing on archaic genes in Turkey found associations with coeliac disease, malaria severity and Costello syndrome. Nonetheless, some genes may have helped modern East Asians adapt to the environment; the putatively Neanderthal Val92Met variant of the MC1R gene, which may be weakly associated with red hair and UV radiation sensitivity, is primarily found in East Asian, rather than European, individuals. Some genes related to the immune system appear to have been affected by introgression, which may have aided migration, such as OAS1, STAT2, TLR6, TLR1, TLR10, and several related to immune response. keratin filaments, sugar metabolism, muscle contraction, body fat distribution, enamel thickness and oocyte meiosis. Nonetheless, a large portion of surviving introgression appears to be non coding ("junk") DNA with few biological functions. A 2016 study indicated that human Neanderthal gene variance may be involved in autism, with chromosome 16 section 16p11.2 deletions playing a large role. A 2017 study reported finding that the more Neanderthal DNA a person has in their genome, the more closely the brain of the individual would resemble that of a Neanderthal. The study also found that parts of the Neanderthal brain related to tool use and visual discrimination may have also experienced evolutionary or adaptational 'trade offs' with the 'social brain', as also found in scientific studies on autism. A 2023 study also found evidence that Neanderthal single nucleotide polymorphisms (SNPs) likely play a "significant role" in autism susceptibility and heritability in autism populations across the United States. According to the study, "Although most studies on autism genomics focus on the deleterious nature of variants, there is the possibility some of these autism associated Neanderthal SNPs have been under weak positive selection. In support, recent studies have identified genetic variants implicated in both autism and high intelligence. Meanwhile, autistic people often perform better on tests of fluid intelligence than neurotypicals." Another 2017 study that analyzed 68 genes associated with neurodevelopmental disorders, including autism, found that these disorders were also affected by natural selection and interbreeding between Homo sapiens and other archaic human species. The study also recommended further research into the link between Neanderthal single nucleotide polymorphisms (SNPs) and neurodevelopmental disorders, including autism, in modern day humans. A 2021 study confirmed these findings, noting that "the protective allele of rs7170637(A) CYFIP1, [one of the genes associated with autism spectrum disorder (ASD)], was present in primates to Neanderthals, and reemerged in modern humans, while absent in early modern humans"; "identified significant positive selection signals in 18 ASD risk SNPs"; that "ancient genome analysis identified de novo mutations representing genes involved in cognitive function and conserved evolutionary selection clusters"; and that "relative enrichment of the ASD risk SNPs from the respective evolutionary cluster or biological interaction networks may help in addressing the phenotypic diversity in ASD", with "cognitive genomic tradeoff signatures impacting the biological networks [explaining] the paradoxical phenotypes in ASD".

Psychologist Bruno Bettelheim believed that autism was linked to early childhood trauma, and his work was highly influential for decades both in the medical and popular spheres. In his discredited theory, he blamed the mothers of individuals with autism for having caused their child's condition through the withholding of affection. Leo Kanner, who first described autism, suggested that parental coldness might contribute to autism. Although Kanner eventually renounced the theory, Bettelheim put an almost exclusive emphasis on it in both his medical and his popular books. Treatments based on these theories failed to help children with autism, and after Bettelheim's death, his reported rates of cure (around 85%) were found to be fraudulent.

The most recent scientific research has determined that changes to brain structures correlated with the development of autism can already be detected while the child is still in the womb, well before any vaccines are administered. Furthermore, scientific studies have consistently refuted a causal relationship between vaccinations and autism. Despite this, some parents believe that vaccinations cause autism; they therefore delay or avoid immunizing their children (for example, under the "vaccine overload" hypothesis that giving many vaccines at once may overwhelm a child's immune system and lead to autism, even though this hypothesis has no scientific evidence and is biologically implausible). Diseases such as measles can cause severe disabilities and even death, so the risk of death or disability for an unvaccinated child is higher than the risk for a child who has been vaccinated. Despite medical evidence, antivaccine activism continues. A developing tactic is the "promotion of irrelevant research to justify the science underlying a questionable claim."

The MMR vaccine as a cause of autism is one of the most extensively debated hypotheses regarding the origins of autism. Andrew Wakefield et al. reported a study of 12 children who had autism and bowel symptoms, in some cases reportedly with onset after MMR. Although the paper, which was later retracted by the journal, concluded that there was no association between the MMR vaccine and autism, Wakefield nevertheless suggested a false notion during a 1998 press conference that giving children the vaccines in three separate doses would be safer than a single dose. Administering the vaccines in three separate doses does not reduce the chance of adverse effects, and it increases the opportunity for infection by the two diseases not immunized against first. The retraction followed an investigation by The Sunday Times, which stated that Wakefield "acted dishonestly and irresponsibly". The Centers for Disease Control and Prevention, the Institute of Medicine of the National Academy of Sciences, and the U. K. National Health Service have all concluded that there is no evidence of a link between the MMR vaccine and autism. In February 2010, The Lancet, which published Wakefield's study, fully retracted it after an independent auditor found the study to be flawed.

Perhaps the best known hypothesis involving mercury and autism involves the use of the mercury based compound thiomersal, a preservative that has been phased out from most childhood vaccinations in developed countries including US and the EU. There is no scientific evidence for a causal connection between thiomersal and autism, but parental concern about a relationship between thiomersal and vaccines has led to decreasing rates of childhood immunizations and increasing likelihood of disease outbreaks. A causal link between thimerosal and autism has been rejected by international scientific and medical professional bodies including the American Medical Association, the American Academy of Pediatrics, the American College of Medical Toxicology, the Canadian Paediatric Society, the U. S. National Academy of Sciences, Centers for Disease Control and Prevention, the Public Health Agency of Canada, and the European Medicines Agency.