Causes of autism
Encyclopedia
Many causes of autism have been proposed, but understanding of the theory of causation
of autism
and the other autism spectrum disorders is incomplete. Heritability
contributes about 90% of the risk of a child developing autism, but the heritability of autism
is complex and typically it is unclear which genes are responsible. In rare cases, autism is strongly associated with agents that cause birth defects
. Many other causes have been proposed, such as childhood immunizations
, but numerous clinical studies have shown no scientific evidence
supporting any link between vaccinations and autism.
involves abnormalities of brain development and behavior which become apparent before a child is three years old and have a steady course with no remission. It is characterized by impairments in social interaction and communication, as well as restricted interests and repetitive behavior; the characterization is independent of any underlying neurological defects. It is part of a larger family called the autism spectrum disorders (ASD) or pervasive developmental disorder
s (PDD), which include closely related syndromes such as Asperger syndrome
and PDD-NOS. This article uses autism to denote the classic autistic disorder and ASD to denote the wider family.
Autism's theory of causation
is still incomplete. It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism's characteristic triad of symptoms. However, there is increasing suspicion among researchers that autism does not have a single cause, but is instead a complex disorder with a set of core aspects that have distinct causes. In other words, completely different underlying brain dysfunctions have been hypothesized to result in the common symptoms of autism, just as completely different brain problems result in mental retardation. The term "the autisms" or "the ASDs" captures the wide range of disease processes at work. Although these distinct causes have been hypothesized to often co-occur, it has also been suggested that the correlation between the causes has been exaggerated. The number of people known to have autism has increased dramatically since the 1980s, at least partly due to changes in diagnostic practice; it is unknown whether prevalence has increased as well.
The consensus among mainstream autism researchers is that genetic factors predominate. Environmental factors that have been claimed to contribute to autism or exacerbate its symptoms, or may be important to consider in future research, include certain foods, infectious disease
, heavy metals
, solvent
s, diesel exhaust
, PCBs
, phthalates
and phenol
s used in plastic
products, pesticide
s, brominated flame retardants, alcohol
, smoking
, illicit drugs, and vaccine
s. Among these factors, vaccines have attracted much attention, as parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and parental concern about vaccines has led to a decreasing uptake of childhood immunizations and an increasing likelihood of measles outbreaks. However, as described in Mercury and MMR vaccine below, there is overwhelming scientific evidence showing no causal association between the measles-mumps-rubella vaccine and autism
, and there is no scientific evidence that the vaccine preservative thiomersal helps cause autism
.
to be over 90%, in other words, that genetics explains over 90% of whether a child will develop autism. This may be an overestimate; new twin data and models with structural genetic variation are needed. 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%.
The genetics
of autism is complex. Linkage analysis has been inconclusive; many association analyses
have had inadequate power. More than one gene
may be implicated, different genes may be involved in different individuals, and the genes may interact with each other or with environmental factors. Several candidate genes have been located, but the mutation
s that increase autism risk have not been identified for most candidate genes. A substantial fraction of autism may be highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome. One hypothesis is that autism is in some sense diametrically opposite to schizophrenia
, and that autism involves increased effects via genomic imprinting of paternally expressed genes that regulate overgrowth in the brain, whereas schizophrenia involves maternally expressed genes and undergrowth.
Though autism's genetic factors
explain most of autism risk, they do not explain all of it. A common hypothesis is that autism is caused by the interaction of a genetic predisposition and an early environmental insult. Several theories based on environmental factors have been proposed to address the remaining risk. Some of these theories focus on prenatal environmental factors, such as agents that cause birth defects; others focus on the environment after birth, such as children's diets.
Risk factors
for autism include parental characteristics such as advanced maternal age
and advanced paternal age. The risk is greater for advanced paternal age. One hypothesis is that this is caused by older sperm that have greater mutation burden; another is that men who carry more genetic liability have some features of autism and therefore marry and have children later. These two hypotheses are not mutually exclusive.
, though these cases are rare.
A child's risk of developing autism is associated with the age of its mother and father at birth. The biological reasons for this are unknown: possible explanations include increased risk of pregnancy complications; maternal autoimmunity
; increased risk of chromosomal abnormalities or unstable trinucleotide repeats in the egg; and imprinted genes, spontaneous mutations, and confounding sociocultural factors in the sperm. Since ages of the father and mother are correlated, it is possible that only the mother's age, or only the father's age, or both, contribute to the risk.
A study of California children born between 1992 and 2002 suggested that second children born at shorter intervals after the first pregnancy were at increased risk of developing autism.
or cytomegalovirus
activates the mother's immune response and greatly increases the risk for autism. Congenital rubella syndrome
is the most convincing environmental cause. Infection-associated immunological events in early pregnancy may affect neural development more than infections in late pregnancy, not only for autism, but also for other psychiatric disorders of presumed neurodevelopmental origin, notably schizophrenia
.
The maternal antibody theory hypothesizes that immunoglobulin G
(IgG) in a mother's blood can cross the placenta
, enter into the fetus's brain, react against fetal brain proteins, and cause autism. The theory is related to the autoimmune disease hypothesis, except it focuses on maternal antibodies rather than the child's. A 2008 study found that these antibodies bind to fetal brain cells, most commonly in mothers of children with regressive autism
. If confirmed, these findings will account for about 12% of autism cases, and, since certain maternal antibody patterns are not found in mothers of typically developing children, it may be possible for mothers to take the antibody test before conception to avoid having an autistic child. A 2008 study found that rhesus monkeys exposed during gestation to IgG from mothers of children with ASD demonstrated stereotypies
, one of the three main symptoms of autism.
, valproic acid
, 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, but evidence is insufficient to determine whether autism risk is actually elevated with ethanol. All known teratogens appear to act during the first eight weeks from conception, and though this does not exclude the possibility that autism can be initiated or affected later, it is strong evidence that autism arises very early in development.
A 2007 study by the California Department of Public Health found that women in the first eight weeks of pregnancy who live near farm fields sprayed with the organochlorine pesticides dicofol
and endosulfan
are several times more likely to give birth to children with autism. The association appeared to increase with dose and decrease with distance from field site to residence. The study's findings suggest that on the order of 7% of autism cases in the California Central Valley
might have been connected to exposure to the insecticides drifting off fields into residential areas. These results are highly preliminary due to the small number of women and children involved and lack of evidence from other studies. It is not known whether these pesticides are human teratogens, though endosulfan has significant teratogenic effects in laboratory rat
s.
A 2005 study showed indirect evidence that prenatal exposure to organophosphate
pesticides such as diazinon
and chlorpyrifos
may contribute to autism in genetically vulnerable children. Several other studies demonstrate the neurodevelopmental toxicity of these agents at relatively low exposure levels.
It has been suggested that exposure during pregnancy to pyrethrin
, a common ingredient in antiflea and antitick pet shampoos, can cause autism in the child. One retrospective study suggesting an association has been conducted, but has not been published.
was associated with a twofold increased risk. Although diabetes causes metabolic and hormonal abnormalities and oxidative stress
, no biological mechanism is known for the association between gestational diabetes and autism risk.
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 flavonoid
s in food, tobacco smoke, and most herbicide
s. This hypothesis has not been tested. A related untested hypothesis is that exposure to pesticides could combine with suboptimal iodine nutrition in a pregnant mother and lead to autism in the child.
Research at UC Davis Medical School has found a link between certain maternal antibodies to fetal brain and autism. One particular pattern of maternal antibodies has only been found in the mothers of autistics, and never in the mothers of typically developing children.
taken during pregnancy could play a role in causing autism by modulating gene expression
through an epigenetic mechanism. This hypothesis is untested.
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.
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. The theory and findings are controversial and many studies contradict the idea that baby boys and girls respond differently to people and objects.
A 2006 study found that sustained exposure of mouse embryos to ultrasound
waves caused a small but statistically significant number of neurons to fail to acquire their proper position during neuronal migration. It is highly unlikely that this result speaks directly to risks of fetal ultrasound as practiced in competent and responsible medical centers. There is no scientific evidence of an association between prenatal ultrasound exposure and autism, but there are very little data on human fetal exposure during diagnostic ultrasound, and the lack of recent epidemiological research and human data in the field has been called "appalling".
found associated obstetric conditions that included low birth weight
and gestation
duration, and hypoxia
during childbirth
. This association does not demonstrate a causal relationship; an underlying cause could explain both autism and these associated conditions. A 2007 study of premature infants found that those who survived cerebellar hemorrhagic injury (bleeding in the brain that injures the cerebellum
) were significantly more likely to show symptoms of autism than controls without the injury.
and extensive further searches for environmental factors are underway.
, based on perceived similarity of symptoms and reports of mercury or its biomarkers in some autistic children. This view has gained little traction in the scientific community as the typical symptoms of mercury toxicity are significantly different than symptoms seen in autism. The principal source of human exposure to organic mercury is via fish consumption and for inorganic mercury is dental amalgams. Other forms of exposure, such as in cosmetics and vaccines, also occur. The evidence so far is indirect for the association between autism and mercury exposure after birth, as no direct test has been reported, and there is no evidence of an association between autism and postnatal exposure to any neurotoxicant. A meta-analysis published in 2007 concluded that there was no link between mercury and autism (based on a literature search by two independent reviewers who did a med-line search from 1980 to 2003).
, a preservative that has been phased out from most childhood vaccination
s in developed countries such as the USA. Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination. There is no scientific evidence for a causal connection between thiomersal and autism, but parental concern about the thiomersal controversy
has led to decreasing rates of childhood immunizations and increasing likelihood of disease outbreaks. Because of public concerns, thiomersal content was completely removed or dramatically reduced from childhood vaccines that contained it in the 1990s; despite this, autism rates continued to climb well into the late 2000s.
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
, the Food and Drug Administration
, Centers for Disease Control and Prevention
, the World Health Organization
, the Public Health Agency of Canada
, and the European Medicines Agency
.
theory of autism is one of the most extensively debated theories 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 "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described," Wakefield nevertheless suggested during a 1998 press conference that giving children the vaccines in three separate doses would be safer than a single dose. This suggestion has been heavily criticized, both on scientific grounds and for triggering a decline in vaccination rates. Using separate, single vaccines in place of MMR is widely believed to put children at increased risk since the combined vaccine reduces the risk of them catching the diseases while they are waiting for full immunization cover. Numerous peer-reviewed studies have also since failed to show any association between MMR vaccine and autism.
In 2004, the interpretation of a causal link between MMR vaccine and autism was formally retracted by ten of Wakefield's twelve co-authors. 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 July 2007 Andrew Wakefield and coauthors John Walker-Smith and Simon Murch faced charges of serious professional misconduct at the General Medical Council
. It is alleged that the trio acted unethically in preparing the research into safety of the MMR vaccine. Wakefield denies the charges. In February 2009 The Sunday Times reported that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.
In 2009, the US Federal Vaccine Court
rejected "speculative and unpersuasive" claims that the MMR vaccine caused autism.
In February 2010, The Lancet, which published Wakefield's study, fully retracted it after an independent auditor found the study to be flawed. In January 2011, an investigation published in the journal BMJ described the Wakefield study as the result of deliberate fraud and manipulation of data.
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 ASD. 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 ASD, and are not always present in ASD, the relationship between immune disturbances and autism remains unclear and controversial.
may have a role in autism, but the evidence so far is anecdotal. Viruses have long been suspected as triggers for immune-mediated diseases such as multiple sclerosis
but showing a direct role for viral causation is difficult in those diseases, and mechanisms whereby viral infections could lead to autism are speculative.
is to some extent the inverse of the viral infection hypothesis: it states that a lack of early childhood exposure to microbes or parasites contributes to autism. This hypothesis relies on some similarities between autism and asthma
and other autoimmune disorders which are already hypothesized to be affected by hygiene: for example, autism and asthma affect more boys than girls, affect more urban than rural children, and are associated with increased neonatal
head circumference. This hypothesis has not been tested scientifically.
may cause autism in some cases. Evidence includes genetic effects on metabolic pathways, reduced antioxidant capacity, enzyme changes, and enhanced biomarkers for oxidative stress; however, the overall evidence is weaker than it is for involvement oxidative stress with disorders such as schizophrenia
. One theory is that stress damages Purkinje cell
s in the cerebellum
after birth, and it is possible that glutathione
is involved.
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.
deficiency, and that recent increases in diagnosed cases of autism are due to medical advice to avoid the sun. The theory has not been studied scientifically.
has been suggested as a possible risk factor for autism, as the lead
blood levels of autistic children has been reported to be significantly higher than typical. The atypical eating behaviors of autistic children, along with habitual mouthing and pica
, make it hard to determine whether increased lead levels are a cause or a consequence of autism.
, his studies' methodology has been criticized, their results have not been replicated by other groups, and Wakefield has been accused of manipulating patient data and misreporting results.
There is no research evidence that autistic children are more likely to have GI symptoms than typical children. In particular, design flaws in studies of elimination diets mean that the data are inadequate to guide treatment recommendations. A 2008 study found that children with autism had no more peptides in their urine than typical children, casting doubt on the proposed mechanism underlying the leaky-gut theory.
In another example, a 1998 study of three children with ASD treated with secretin
infusion reported improved GI function and dramatic improvement in behavior, which suggested an association between GI and brain function in autistic children, although the low number of patients is statistically insignificant. After this study, many parents sought secretin treatment and a black market for the hormone developed quickly. However, later studies found secretin ineffective in treating autism.
(acetaminophen, Tylenol) following MMR vaccine is apparently associated with development of autism
in children aged 1–5 years. The effect has not been independently confirmed. More evidence for the hypothesis is that in the U.S. paracetamol began to replace aspirin
for infants and young children in the 1980s, about the same time that the number of known autism cases began to rise. However, a similar rise in autism occurred in France, where children continued to receive aspirin.
was associated with autism by examining county-level autism data for California, Oregon, and Washington. Noel S. Weiss was highly critical of the publication of this work in an editorial published in the same journal, and argued that it is possible that nonprofessionals will misinterpret this result, and that it may not lead to insights about the causes of autism.
believed that autism was linked to early childhood trauma, and his work was highly influential for decades both in the medical and popular spheres. Parents, especially mothers, of individuals with autism were blamed 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, it came out that his reported rates of cure (around 85%) were found to be fraudulent.
Asperger syndrome
and high-functioning 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.
abilities. Evolutionary psychological
explanations for these sex differences include that moderate systemizing would be helpful for male dominated activities such as hunting while empathizing would be similarly helpful in female dominated activities such as caring for children. However, extreme systemizing in combination with low empathizing would lead to autism. One explanation for the increased prevalence of autism may be increased assortative mating
between high systemizers.
The "imprinted brain theory
" is a somewhat similar but not identical theory that considers autism and psychosis
to be contrasting disorders on a number of different variables. This is argued to caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and the other autism spectrum disorders is incomplete. Heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
contributes about 90% of the risk of a child developing autism, but the heritability of autism
Heritability of autism
The heritability of autism is the proportion of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic...
is complex and typically it is unclear which genes are responsible. In rare cases, autism is strongly associated with agents that cause birth defects
Teratology
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants.- Etymology :The...
. Many other causes have been proposed, such as childhood immunizations
Vaccination schedule
A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence....
, but numerous clinical studies have shown no scientific evidence
Evidence-based medicine
Evidence-based medicine or evidence-based practice aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments and diagnostic tests...
supporting any link between vaccinations and autism.
Autism and related disorders
AutismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
involves abnormalities of brain development and behavior which become apparent before a child is three years old and have a steady course with no remission. It is characterized by impairments in social interaction and communication, as well as restricted interests and repetitive behavior; the characterization is independent of any underlying neurological defects. It is part of a larger family called the autism spectrum disorders (ASD) or pervasive developmental disorder
Pervasive developmental disorder
Pervasive developmental disorders is a diagnostic category refers to a group of disorders characterized by delays or impairments in communication, social behaviors, and cognitive development.Pervasive developmental disorders include Autism, Asperger's syndrome, Rett's syndrome, Childhood...
s (PDD), which include closely related syndromes such as Asperger syndrome
Asperger syndrome
Asperger's syndrome that is characterized by significant difficulties in social interaction, alongside restricted and repetitive patterns of behavior and interests. It differs from other autism spectrum disorders by its relative preservation of linguistic and cognitive development...
and PDD-NOS. This article uses autism to denote the classic autistic disorder and ASD to denote the wider family.
Autism's theory of causation
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
is still incomplete. It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism's characteristic triad of symptoms. However, there is increasing suspicion among researchers that autism does not have a single cause, but is instead a complex disorder with a set of core aspects that have distinct causes. In other words, completely different underlying brain dysfunctions have been hypothesized to result in the common symptoms of autism, just as completely different brain problems result in mental retardation. The term "the autisms" or "the ASDs" captures the wide range of disease processes at work. Although these distinct causes have been hypothesized to often co-occur, it has also been suggested that the correlation between the causes has been exaggerated. The number of people known to have autism has increased dramatically since the 1980s, at least partly due to changes in diagnostic practice; it is unknown whether prevalence has increased as well.
The consensus among mainstream autism researchers is that genetic factors predominate. Environmental factors that have been claimed to contribute to autism or exacerbate its symptoms, or may be important to consider in future research, include certain foods, infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
, heavy metals
Heavy metals
A heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...
, solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
s, diesel exhaust
Diesel exhaust
Diesel exhaust is the exhaust gas of a diesel engine....
, PCBs
Polychlorinated biphenyl
Polychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...
, phthalates
Phthalates
Phthalates , or phthalate esters, are esters of phthalic acid and are mainly used as plasticizers . They are used primarily to soften polyvinyl chloride...
and phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
s used in plastic
Plastic
A plastic material is any of a wide range of synthetic or semi-synthetic organic solids used in the manufacture of industrial products. Plastics are typically polymers of high molecular mass, and may contain other substances to improve performance and/or reduce production costs...
products, pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...
s, brominated flame retardants, alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, smoking
Smoking
Smoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...
, illicit drugs, and vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s. Among these factors, vaccines have attracted much attention, as parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and parental concern about vaccines has led to a decreasing uptake of childhood immunizations and an increasing likelihood of measles outbreaks. However, as described in Mercury and MMR vaccine below, there is overwhelming scientific evidence showing no causal association between the measles-mumps-rubella vaccine and autism
MMR vaccine controversy
The MMR vaccine controversy was a case of scientific misconduct which triggered a health scare. It followed the publication in 1998 of a paper in the medical journal The Lancet which presented apparent evidence that autism spectrum disorders could be caused by the MMR vaccine, an immunization...
, and there is no scientific evidence that the vaccine preservative thiomersal helps cause autism
Thiomersal controversy
The thiomersal controversy describes claims that vaccines containing the mercury-based preservative thiomersal contribute to the development of autism and other brain development disorders...
.
Genetics
Genetic factors are the most significant cause for autism spectrum disorders. Early studies of twins estimated heritabilityHeritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
to be over 90%, in other words, that genetics explains over 90% of whether a child will develop autism. This may be an overestimate; new twin data and models with structural genetic variation are needed. 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%.
The genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
of autism is complex. Linkage analysis has been inconclusive; many association analyses
Genetic association
Genetic association is the occurrence, more often than can be readily explained by chance, of two or more traits in a population of individuals, of which at least one trait is known to be genetic....
have had inadequate power. More than one gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
may be implicated, different genes may be involved in different individuals, and the genes may interact with each other or with environmental factors. Several candidate genes have been located, but the mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s that increase autism risk have not been identified for most candidate genes. A substantial fraction of autism may be highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome. One hypothesis is that autism is in some sense diametrically opposite to schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, and that autism involves increased effects via genomic imprinting of paternally expressed genes that regulate overgrowth in the brain, whereas schizophrenia involves maternally expressed genes and undergrowth.
Though autism's genetic factors
Heritability of autism
The heritability of autism is the proportion of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic...
explain most of autism risk, they do not explain all of it. A common hypothesis is that autism is caused by the interaction of a genetic predisposition and an early environmental insult. Several theories based on environmental factors have been proposed to address the remaining risk. Some of these theories focus on prenatal environmental factors, such as agents that cause birth defects; others focus on the environment after birth, such as children's diets.
Risk factors
Risk factors
A risk factor is a concept in finance theory such as the CAPM, APT and other theories that use pricing kernels. In these models, the rate of return of an asset is a random variable whose realization in any time period is a linear combination of other random variables plus a disturbance term or...
for autism include parental characteristics such as advanced maternal age
Advanced maternal age
Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....
and advanced paternal age. The risk is greater for advanced paternal age. One hypothesis is that this is caused by older sperm that have greater mutation burden; another is that men who carry more genetic liability have some features of autism and therefore marry and have children later. These two hypotheses are not mutually exclusive.
Prenatal environment
The risk of autism is associated with several prenatal risk factors, including advanced age in either parent, and diabetes, bleeding, and use of psychiatric drugs in the mother during pregnancy. Autism has been linked to birth defect agents acting during the first eight weeks from conceptionHuman fertilization
Human fertilization is the union of a humanoid egg and sperm, usually occurring in the ampulla of the uterine tube. The result of this union is the production of a zygote, or fertilized egg, initiating prenatal development...
, though these cases are rare.
A child's risk of developing autism is associated with the age of its mother and father at birth. The biological reasons for this are unknown: possible explanations include increased risk of pregnancy complications; maternal autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
; increased risk of chromosomal abnormalities or unstable trinucleotide repeats in the egg; and imprinted genes, spontaneous mutations, and confounding sociocultural factors in the sperm. Since ages of the father and mother are correlated, it is possible that only the mother's age, or only the father's age, or both, contribute to the risk.
A study of California children born between 1992 and 2002 suggested that second children born at shorter intervals after the first pregnancy were at increased risk of developing autism.
Infectious processes
Prenatal viral infection has been called the principal non-genetic cause of autism. Prenatal exposure to rubellaRubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
or cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
activates the mother's immune response and greatly increases the risk for autism. Congenital rubella syndrome
Congenital rubella syndrome
Congenital rubella syndrome can occur in a developing fetus of a pregnant woman who has contracted rubella during her first trimester. If infection occurs 0–28 days before conception, there is a 43% chance the infant will be affected. If the infection occurs 0–12 weeks after conception, there is a...
is the most convincing environmental cause. Infection-associated immunological events in early pregnancy may affect neural development more than infections in late pregnancy, not only for autism, but also for other psychiatric disorders of presumed neurodevelopmental origin, notably schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
The maternal antibody theory hypothesizes that immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
(IgG) in a mother's blood can cross the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
, enter into the fetus's brain, react against fetal brain proteins, and cause autism. The theory is related to the autoimmune disease hypothesis, except it focuses on maternal antibodies rather than the child's. A 2008 study found that these antibodies bind to fetal brain cells, most commonly in mothers of children with regressive autism
Regressive autism
Regressive autism occurs when a child appears to develop typically but then starts to lose speech and social skills, typically between the ages of 15 and 30 months, and is subsequently diagnosed with autism...
. If confirmed, these findings will account for about 12% of autism cases, and, since certain maternal antibody patterns are not found in mothers of typically developing children, it may be possible for mothers to take the antibody test before conception to avoid having an autistic child. A 2008 study found that rhesus monkeys exposed during gestation to IgG from mothers of children with ASD demonstrated stereotypies
Stereotypy
A stereotypy is a repetitive or ritualistic movement, posture, or utterance, found in people with mental retardation, autism spectrum disorders, tardive dyskinesia and stereotypic movement disorder. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing,...
, one of the three main symptoms of autism.
Environmental agents
Teratogens are environmental agents that cause birth defects. Some agents that are theorized to cause other 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 thalidomideThalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
, valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
, or misoprostol
Misoprostol
Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D...
. These cases are rare. Questions have also been raised whether ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
(grain alcohol) increases autism risk, as part of fetal alcohol syndrome
Fetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
or alcohol-related birth defects, but evidence is insufficient to determine whether autism risk is actually elevated with ethanol. All known teratogens appear to act during the first eight weeks from conception, and though this does not exclude the possibility that autism can be initiated or affected later, it is strong evidence that autism arises very early in development.
A 2007 study by the California Department of Public Health found that women in the first eight weeks of pregnancy who live near farm fields sprayed with the organochlorine pesticides dicofol
Dicofol
Dicofol is an organochlorine pesticide that is chemically related to DDT. Dicofol is a miticide that is very effective against red spider mite....
and endosulfan
Endosulfan
Endosulfan is an off-patent organochlorine insecticide and acaricide that is being phased out globally. Endosulfan became a highly controversial agrichemical due to its acute toxicity, potential for bioaccumulation, and role as an endocrine disruptor...
are several times more likely to give birth to children with autism. The association appeared to increase with dose and decrease with distance from field site to residence. The study's findings suggest that on the order of 7% of autism cases in the California Central Valley
California Central Valley
California's Central Valley is a large, flat valley that dominates the central portion of California. It is home to California's most productive agricultural efforts. The valley stretches approximately from northwest to southeast inland and parallel to the Pacific Ocean coast. Its northern half is...
might have been connected to exposure to the insecticides drifting off fields into residential areas. These results are highly preliminary due to the small number of women and children involved and lack of evidence from other studies. It is not known whether these pesticides are human teratogens, though endosulfan has significant teratogenic effects in laboratory rat
Laboratory rat
A laboratory rat is a rat of the species Rattus norvegicus which is bred and kept for scientific research. Laboratory rats have served as an important animal model for research in psychology, medicine, and other fields.- Origins :...
s.
A 2005 study showed indirect evidence that prenatal exposure to organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
pesticides such as diazinon
Diazinon
Diazinon , a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company...
and chlorpyrifos
Chlorpyrifos
Chlorpyrifos is a crystalline organophosphate insecticide that inhibits acetylcholinesterase and is used to control insect pests. It is known by many trade names...
may contribute to autism in genetically vulnerable children. Several other studies demonstrate the neurodevelopmental toxicity of these agents at relatively low exposure levels.
It has been suggested that exposure during pregnancy to pyrethrin
Pyrethrin
The pyrethrins are a pair of natural organic compounds that have potent insecticidal activity. Pyrethrins are neurotoxins that attack the nervous systems of all insects. When present in amounts not fatal to insects, they still appear to have an insect repellent effect. Pyrethrins are gradually...
, a common ingredient in antiflea and antitick pet shampoos, can cause autism in the child. One retrospective study suggesting an association has been conducted, but has not been published.
Other maternal conditions
Diabetes in the mother during pregnancy is a significant risk factor for autism; a 2009 meta-analysis found that gestational diabetesGestational diabetes
Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy . It is widely accepted as a disease only in the United States, there is some question whether the condition is natural during pregnancy...
was associated with a twofold increased risk. Although diabetes causes metabolic and hormonal abnormalities and oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
, no biological mechanism is known for the association between gestational diabetes and autism risk.
Thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
problems that lead to thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
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
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
in the diet, and by environmental agents that interfere with iodine uptake
Goitrogen
Goitrogens are substances that suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of the thyroid, i.e., a goitre.-Goitrogenic drugs and chemicals:...
or act against thyroid hormones
Antithyroid agent
An antithyroid agent is a hormone antagonist acting upon thyroid hormones.The main antithyroid drugs are carbimazole , methimazole , and propylthiouracil/PTU...
. Possible environmental agents include flavonoid
Flavonoid
Flavonoids , are a class of plant secondary metabolites....
s in food, tobacco smoke, and most herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...
s. This hypothesis has not been tested. A related untested hypothesis is that exposure to pesticides could combine with suboptimal iodine nutrition in a pregnant mother and lead to autism in the child.
Research at UC Davis Medical School has found a link between certain maternal antibodies to fetal brain and autism. One particular pattern of maternal antibodies has only been found in the mothers of autistics, and never in the mothers of typically developing children.
Other in utero
It has been hypothesized that folic acidFolic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
taken during pregnancy could play a role in causing autism by modulating gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
through an epigenetic mechanism. This hypothesis is untested.
Prenatal stress
Prenatal stress
Prenatal stress is exposure of an expectant mother to distress, which can be caused by stressful life events or by environmental hardships. The resulting changes to the mother's hormonal and immune system may harm the fetus's immune function and brain development....
, 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.
The fetal testosterone theory hypothesizes that higher levels of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
in the amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of 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. The theory and findings are controversial and many studies contradict the idea that baby boys and girls respond differently to people and objects.
A 2006 study found that sustained exposure of mouse embryos to ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
waves caused a small but statistically significant number of neurons to fail to acquire their proper position during neuronal migration. It is highly unlikely that this result speaks directly to risks of fetal ultrasound as practiced in competent and responsible medical centers. There is no scientific evidence of an association between prenatal ultrasound exposure and autism, but there are very little data on human fetal exposure during diagnostic ultrasound, and the lack of recent epidemiological research and human data in the field has been called "appalling".
Perinatal environment
Autism is associated with some perinatal and obstetric conditions. A 2007 review of risk factorsRisk factors
A risk factor is a concept in finance theory such as the CAPM, APT and other theories that use pricing kernels. In these models, the rate of return of an asset is a random variable whose realization in any time period is a linear combination of other random variables plus a disturbance term or...
found associated obstetric conditions that included low birth weight
Low birth weight
Low birth weight is defined as a birth weight of a liveborn infant of less than 2,500 g. regardless of gestational age-Causes:LBW is either the result of preterm birth or of the infant being small for gestational age , or a combination of...
and gestation
Gestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
duration, and hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
during childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
. This association does not demonstrate a causal relationship; an underlying cause could explain both autism and these associated conditions. A 2007 study of premature infants found that those who survived cerebellar hemorrhagic injury (bleeding in the brain that injures the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
) were significantly more likely to show symptoms of autism than controls without the injury.
Postnatal environment
A wide variety of postnatal contributors to autism have been proposed, including gastrointestinal or immune system abnormalities, allergies, and exposure of children to drugs, vaccines, infection, certain foods, or heavy metals. The evidence for these risk factors is anecdotal and has not been confirmed by reliable studies. The subject remains controversialControversies in autism
Controversies in autism encompass the disagreement over the exact nature of autism, its causes and manifestations. Autism is considered to be a neurodevelopmental condition which manifests itself in markedly abnormal social interaction, communication ability, and patterns of interests.The cause of...
and extensive further searches for environmental factors are underway.
Mercury
This theory hypothesizes that autism is associated with mercury poisoningMercury poisoning
Mercury poisoning is a disease caused by exposure to mercury or its compounds. Mercury is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses...
, based on perceived similarity of symptoms and reports of mercury or its biomarkers in some autistic children. This view has gained little traction in the scientific community as the typical symptoms of mercury toxicity are significantly different than symptoms seen in autism. The principal source of human exposure to organic mercury is via fish consumption and for inorganic mercury is dental amalgams. Other forms of exposure, such as in cosmetics and vaccines, also occur. The evidence so far is indirect for the association between autism and mercury exposure after birth, as no direct test has been reported, and there is no evidence of an association between autism and postnatal exposure to any neurotoxicant. A meta-analysis published in 2007 concluded that there was no link between mercury and autism (based on a literature search by two independent reviewers who did a med-line search from 1980 to 2003).
Vaccines
The scientific consensus is that there is no evidence of a causal relationship between vaccinations and autism. Despite this, many parents believe that vaccinations cause autism and therefore delay or avoid immunizing their children 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. As diseases like measles can cause severe disabilities and death, the risk of a child's death or disability due to not vaccinating a child is significantly larger than any minuscule risks due to vaccinating.Thiomersal
Perhaps the best-known hypothesis involving mercury and autism involves the use of the mercury-based compound thiomersalThiomersal
Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....
, a preservative that has been phased out from most childhood vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
s in developed countries such as the USA. Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination. There is no scientific evidence for a causal connection between thiomersal and autism, but parental concern about the thiomersal controversy
Thiomersal controversy
The thiomersal controversy describes claims that vaccines containing the mercury-based preservative thiomersal contribute to the development of autism and other brain development disorders...
has led to decreasing rates of childhood immunizations and increasing likelihood of disease outbreaks. Because of public concerns, thiomersal content was completely removed or dramatically reduced from childhood vaccines that contained it in the 1990s; despite this, autism rates continued to climb well into the late 2000s.
A causal link between thimerosal and autism has been rejected by international scientific and medical professional bodies including the American Medical Association
American Medical Association
The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
, the American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
, the American College of Medical Toxicology
American College of Medical Toxicology
The American College of Medical Toxicology , founded in 1993, is the largest organization of medical toxicologists in the United States and the world....
, the Canadian Paediatric Society
Canadian Paediatric Society
The Canadian Paediatric Society is a national association of paediatricians, committed to working together to advance the health of children and youth by nurturing excellence in health care, advocacy, education, research and support of its membership....
, the U.S. National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
, Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
, the Public Health Agency of Canada
Public Health Agency of Canada
The Public Health Agency of Canada is an agency of the Government of Canada that is responsible for public health, emergency preparedness, and response and infectious and chronic disease control and prevention...
, and the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
.
MMR vaccine
The MMR vaccineMMR vaccine
The MMR vaccine is an immunization shot against measles, mumps, and rubella . It was first developed by Maurice Hilleman while at Merck in the late 1960s....
theory of autism is one of the most extensively debated theories regarding the origins of autism. Andrew Wakefield
Andrew Wakefield
Andrew Wakefield is a British former surgeon and medical researcher, known as an advocate for the discredited claim that there is a link between the measles, mumps and rubella vaccine, autism and bowel disease, and for his fraudulent 1998 research paper in support of that claim.Four years after...
et al. reported a study of 12 children who had autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and bowel symptoms, in some cases reportedly with onset after MMR. Although the paper, which was later retracted by the journal, concluded "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described," Wakefield nevertheless suggested during a 1998 press conference that giving children the vaccines in three separate doses would be safer than a single dose. This suggestion has been heavily criticized, both on scientific grounds and for triggering a decline in vaccination rates. Using separate, single vaccines in place of MMR is widely believed to put children at increased risk since the combined vaccine reduces the risk of them catching the diseases while they are waiting for full immunization cover. Numerous peer-reviewed studies have also since failed to show any association between MMR vaccine and autism.
In 2004, the interpretation of a causal link between MMR vaccine and autism was formally retracted by ten of Wakefield's twelve co-authors. The retraction followed an investigation by The Sunday Times
The Sunday Times
The Sunday Times is a British Sunday newspaper.The Sunday Times may also refer to:*The Sunday Times *The Sunday Times *The Sunday Times *The Sunday Times...
, which stated that Wakefield "acted dishonestly and irresponsibly". The Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
, the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
of the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
, and the U.K. National Health Service
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
have all concluded that there is no evidence of a link between the MMR vaccine and autism.
In July 2007 Andrew Wakefield and coauthors John Walker-Smith and Simon Murch faced charges of serious professional misconduct at the General Medical Council
General Medical Council
The General Medical Council registers and regulates doctors practising in the United Kingdom. It has the power to revoke or restrict a doctor's registration if it deems them unfit to practise...
. It is alleged that the trio acted unethically in preparing the research into safety of the MMR vaccine. Wakefield denies the charges. In February 2009 The Sunday Times reported that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.
In 2009, the US Federal Vaccine Court
Vaccine court
Vaccine court is the popular term which refers to the Office of Special Masters of the U.S. Court of Federal Claims, which administers a no-fault system for litigating vaccine injury claims. These claims against vaccine manufacturers cannot normally be filed in state or federal civil courts, but...
rejected "speculative and unpersuasive" claims that the MMR vaccine caused autism.
In February 2010, The Lancet, which published Wakefield's study, fully retracted it after an independent auditor found the study to be flawed. In January 2011, an investigation published in the journal BMJ described the Wakefield study as the result of deliberate fraud and manipulation of data.
Autoimmune disease
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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and the nervous system begin early during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
, 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 ASD. 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 ASD, and are not always present in ASD, the relationship between immune disturbances and autism remains unclear and controversial.
Viral infection
Many studies have presented evidence for and against association of autism with viral infection after birth. Laboratory rats infected with Borna disease virus show some symptoms similar to those of autism but blood studies of autistic children show no evidence of infection by this virus. Members of the herpes virus familyHerpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
may have a role in autism, but the evidence so far is anecdotal. Viruses have long been suspected as triggers for immune-mediated diseases such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
but showing a direct role for viral causation is difficult in those diseases, and mechanisms whereby viral infections could lead to autism are speculative.
Excessive hygiene
The hygiene hypothesisHygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
is to some extent the inverse of the viral infection hypothesis: it states that a lack of early childhood exposure to microbes or parasites contributes to autism. This hypothesis relies on some similarities between autism and asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
and other autoimmune disorders which are already hypothesized to be affected by hygiene: for example, autism and asthma affect more boys than girls, affect more urban than rural children, and are associated with increased neonatal
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
head circumference. This hypothesis has not been tested scientifically.
Oxidative stress
This theory hypothesizes that toxicity and oxidative stressOxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
may cause autism in some cases. Evidence includes genetic effects on metabolic pathways, reduced antioxidant capacity, enzyme changes, and enhanced biomarkers for oxidative stress; however, the overall evidence is weaker than it is for involvement oxidative stress with disorders such as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. One theory is that stress damages Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s in the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
after birth, and it is possible that glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
is involved.
Amygdala neurons
This theory hypothesizes that an early developmental failure involving the amygdalaAmygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
cascades on the development of cortical areas that mediate social perception in the visual domain. The fusiform face area
Fusiform face area
The fusiform face area is a part of the human visual system which might be specialized for facial recognition, although there is some evidence that it also processes categorical information about other objects, particularly familiar ones.-Localization:...
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.
Locus coeruleus–noradrenergic system
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.Lack of Vitamin D
This theory hypothesizes that autism is caused by vitamin DVitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
deficiency, and that recent increases in diagnosed cases of autism are due to medical advice to avoid the sun. The theory has not been studied scientifically.
Lead
Lead poisoningLead poisoning
Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
has been suggested as a possible risk factor for autism, as the lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
blood levels of autistic children has been reported to be significantly higher than typical. The atypical eating behaviors of autistic children, along with habitual mouthing and pica
Pica (disorder)
Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...
, make it hard to determine whether increased lead levels are a cause or a consequence of autism.
Leaky gut syndrome
Parents have reported gastrointestinal (GI) disturbances in autistic children, and several studies have investigated possible associations between autism and the gut. The disputed Wakefield et al. paper also suggested that some bowel disorders may allow antigens to pass from food into the bloodstream and then to contribute to brain dysfunction. Although Wakefield later proposed the term autistic enterocolitisAutistic enterocolitis
"Autistic enterocolitis" is a controversial term first used by discredited British gastroenterologist Andrew Wakefield to describe a number of common clinical symptoms and signs which he contends are distinctive to autism...
, his studies' methodology has been criticized, their results have not been replicated by other groups, and Wakefield has been accused of manipulating patient data and misreporting results.
There is no research evidence that autistic children are more likely to have GI symptoms than typical children. In particular, design flaws in studies of elimination diets mean that the data are inadequate to guide treatment recommendations. A 2008 study found that children with autism had no more peptides in their urine than typical children, casting doubt on the proposed mechanism underlying the leaky-gut theory.
In another example, a 1998 study of three children with ASD treated with secretin
Secretin
Secretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
infusion reported improved GI function and dramatic improvement in behavior, which suggested an association between GI and brain function in autistic children, although the low number of patients is statistically insignificant. After this study, many parents sought secretin treatment and a black market for the hormone developed quickly. However, later studies found secretin ineffective in treating autism.
Paracetamol
A 2008 preliminary case-control study based on a parent survey presented evidence that paracetamolParacetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen, Tylenol) following MMR vaccine is apparently associated with development of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
in children aged 1–5 years. The effect has not been independently confirmed. More evidence for the hypothesis is that in the U.S. paracetamol began to replace aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
for infants and young children in the 1980s, about the same time that the number of known autism cases began to rise. However, a similar rise in autism occurred in France, where children continued to receive aspirin.
Rain
It has been hypothesized that rain, or some environmental trigger positively associated with rain, acts together with an underlying genetic predisposition to cause autism. A 2008 study found that precipitationPrecipitation (meteorology)
In meteorology, precipitation In meteorology, precipitation In meteorology, precipitation (also known as one of the classes of hydrometeors, which are atmospheric water phenomena is any product of the condensation of atmospheric water vapor that falls under gravity. The main forms of precipitation...
was associated with autism by examining county-level autism data for California, Oregon, and Washington. Noel S. Weiss was highly critical of the publication of this work in an editorial published in the same journal, and argued that it is possible that nonprofessionals will misinterpret this result, and that it may not lead to insights about the causes of autism.
Refrigerator mother
Bruno BettelheimBruno Bettelheim
Bruno Bettelheim was an Austrian-born American child psychologist and writer. He gained an international reputation for his work on Freud, psychoanalysis, and emotionally disturbed children.-Background:...
believed that autism was linked to early childhood trauma, and his work was highly influential for decades both in the medical and popular spheres. Parents, especially mothers, of individuals with autism were blamed for having caused their child's condition through the withholding of affection. Leo Kanner
Leo Kanner
Leo Kanner was a Jewish American psychiatrist and physician known for his work related to autism. Kanner's work formed the foundation of child and adolescent psychiatry in the U.S. and worldwide....
, 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, it came out that his reported rates of cure (around 85%) were found to be fraudulent.
Other psychogenic theories
Psychogenic theories in general have become increasingly unpopular, particularly since twin studies have shown that autism is highly heritable. Nevertheless, some case reports have found that deep institutional privation can result in "quasi-autistic" features without the neuroanatomical differences. Other case reports have suggested that children predisposed genetically to autism can develop "autistic devices" in response to traumatic events such as the birth of a sibling.Social construct
Like ADHD, which has a similar social construct theory, a spectral disorder such as autism may be understood as a cultural or social construct. The theory says that the boundary between normal and abnormal is subjective and arbitrary, so autism does not exist as an objective entity, but only as a social construct. It further argues that autistic individuals themselves have a way of being that is partly socially constructed.Asperger syndrome
Asperger syndrome
Asperger's syndrome that is characterized by significant difficulties in social interaction, alongside restricted and repetitive patterns of behavior and interests. It differs from other autism spectrum disorders by its relative preservation of linguistic and cognitive development...
and high-functioning autism
High-functioning autism
High-functioning autism is an informal term applied to autistic people who are deemed to be "higher functioning" than other autistic people, by one or more metrics. There is no consensus as to the definition. HFA is not yet a recognised diagnosis in the DSM-IV-TR or the ICD-10.The amount of...
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.
Evolutionary psychology
The "extreme male brain theory" of autism views autism as an extreme version of male-female differences regarding "systemizing" and empathizingEmpathy
Empathy is the capacity to recognize and, to some extent, share feelings that are being experienced by another sapient or semi-sapient being. Someone may need to have a certain amount of empathy before they are able to feel compassion. The English word was coined in 1909 by E.B...
abilities. Evolutionary psychological
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...
explanations for these sex differences include that moderate systemizing would be helpful for male dominated activities such as hunting while empathizing would be similarly helpful in female dominated activities such as caring for children. However, extreme systemizing in combination with low empathizing would lead to autism. One explanation for the increased prevalence of autism may be increased assortative mating
Assortative mating
Assortative mating , and the related concept Disassortative mating, is the phenomenon where a sexually reproducing organism chooses to mate with individuals that are similar or dissimilar to itself in some specific manner...
between high systemizers.
The "imprinted brain theory
Imprinted brain theory
The imprinted brain theory is an evolutionary psychology theory regarding the causes of autism spectrum disorders and psychosis.- The conflict theory of imprinting :...
" is a somewhat similar but not identical theory that considers autism and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
to be contrasting disorders on a number of different variables. This is argued to caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.