Misplaced Pages

This is an old revision of this page, as edited by Eubulides (talk | contribs) at 06:16, 14 February 2009 (Update URLs that have moved. Remove dangling lnk to pm.gov.uk (Gordon Brown cleaned house, perhaps?) along with claim that it supports.). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Autism and autism spectrum disorders are complex neurodevelopmental disorders. Many causes of autism have been proposed, but its theory of causation is still incomplete. Heritability contributes about 90% of the risk of a child developing autism, but the genetics of autism are 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 exposure of children to vaccines; these proposals are controversial and the vaccine hypotheses have no convincing scientific evidence.

Autism and related disorders

Autism is a condition involving abnormalities of brain development and behavior which manifests itself before a child is three years old and has a steady course with no remission. It is characterized by impairments in social interaction and communication, as well as restricted and repetitive behavior. It is part of a larger family called the autism spectrum disorders (ASD) or pervasive developmental disorders (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. 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. An increase in prevalence would suggest directing more attention and funding toward changing environmental factors instead of continuing to focus on genetics.

The consensus among mainstream autism researchers is that genetic factors predominate, but some are concerned, as one anonymous researcher put it, that "geneticists are running the show, and ignoring the environmental aspects." 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, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, and vaccines. 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.

In 2007 the National Institutes of Health announced an Autism Centers of Excellence (ACE) research program to find the causes of autism and identify new treatments for the disorder. Initial recipients are focusing on genetic factors, brain imaging, brain chemicals and functions including mirror neurons, effect of early parent-child behavior on autism, and learning in autistic children.

Genetics

Genetic factors are the most significant cause for autism spectrum disorders. Early studies of twins estimated heritability 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 mutations 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.

A 2007 review of risk factors found associated parental characteristics that included advanced maternal age, advanced paternal age, and maternal place of birth outside Europe or North America. It is not known whether these associations reflect genetic, epigenetic, or environmental factors.

Prenatal environment

The risk of autism is associated with several prenatal risk factors. Autism has been linked to birth defect agents acting during the first eight weeks from conception, though these cases are rare. Other potential prenatal environmental factors do not have convincing scientific evidence.

Maternal infection

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 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. 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.

Teratogens

Teratogens are environmental agents that cause birth defects. Some agents that are known to cause other birth defects have also been found to be related to autism risk. These include exposure of the embryo to thalidomide, 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 current 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.

Pesticides

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 rats.

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.

Thyroid problems

Thyroid problems that lead to thyroxine deficiency in the mother in weeks 8–12 of pregnancy has 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.

Folic acid

It has been hypothesized that folic acid taken during pregnancy could play a role in causing autism by modulating gene expression through epigenetic mechanism. This hypothesis is untested.

Stress

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.

Fetal testosterone

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 EQ SQ 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.

Ultrasound

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".

Perinatal environment

Autism is associated with some perinatal and obstetric conditions. A 2007 review of risk factors 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.

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 controversial and extensive further searches for environmental factors are underway.

Autoimmune disease

This theory hypothesizes that autoantibodies that target the brain may cause or exacerbate autism. It is related to the maternal antibodies 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. Several symptoms consistent with a poorly regulated immune response have been reported in autistic children. It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD. As autoantibodies have not been associated with pathology, 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.

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 controversial Wakefield et al. vaccine paper discussed in MMR vaccine below 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 enterocolitis, 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.

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. 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.

Leaky gut syndrome theories inspired several dietary treatments, including gluten-free diets, casein-free diets, antifungal diets, low-sugar diets, as well as supplements that include nystatin, B₁₂, and probiotics. Parents are more likely to get advice about these diets from other parents, the media, and the Internet than from medical experts. There is no solid 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 currently available 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.

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 family 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.

Excessive hygiene

The hygiene hypothesis 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 head circumference. This hypothesis has not been tested scientifically.

Oxidative stress

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; 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 cells in the cerebellum after birth, and it is possible that glutathione is involved.

Amygdala neurons

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.

Vitamin D

This theory hypothesizes that autism is caused by vitamin D 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 poisoning 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.

Mercury

This theory hypothesizes that autism is associated with mercury poisoning, based on perceived similarity of symptoms and reports of mercury or its biomarkers in some autistic children. 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.

There is little evidence of an increased body burden of mercury in autistic children. A 2003 study reported that mercury measurements of hair samples from autistic children's first haircuts were significantly lower than a matched group of normal children, declining as measures of severity increased, but a later meta-analysis based on two studies found that there was not enough evidence to conclude that hair mercury level is lower in autistic children. A 2006 study found a slight association between autism and environmental releases of mercury, primarily from coal power plants; this study used Texas county-wide data and did not distinguish between prenatal and postnatal exposure. A 2009 followup study found a similar slight association between autism rates and distance to industrial and power plant mercury sources in Texas.

Perhaps the best-known theory 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. Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination. There is no convincing scientific evidence for a causal connection between thiomersal and autism, but parental concern about the thiomersal controversy has led to decreasing uptake of childhood immunizations and increasing likelihood of disease outbreaks.

MMR vaccine

The MMR vaccine theory of autism is one of the most extensively debated theories regarding the origins of autism. A controversial 1998 paper by Andrew Wakefield et al. reported a study of 12 children who had autism and bowel symptoms, in some cases reportedly with onset after MMR. Though the paper 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 jab. 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 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.

Paracetamol

A 2008 preliminary case-control study based on a parent survey presented evidence that paracetamol (acetaminophen) following MMR vaccine is apparently associated with development of autism in children aged 1–5 years. The effect has not been independently confirmed.

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 precipitation was associated with autism by examining county-level autism data for California, Oregon, and Washington. It is possible that nonprofessionals will misinterpret this result, and that it may well not lead to insights about the causes of autism.

Precipitation is also associated with television watching, and a 2006 analysis by three of the same authors, all economists, concluded that just under 40% of autism diagnoses in the three states result from television watching due to precipitation. The previous study was widely publicized but was not published in a refereed journal, and was strongly criticized on several grounds, including confusing association with causality: one environmental health researcher wrote, "Little details like the 'ecological fallacy,' confounding, and exposure assessment apparently do not apply in the world of economists, and all associations are causal in this parallel universe."

Refrigerator mother

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. 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.

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. This theory does not say that there are no neurological or quality-of-life differences between groups deemed "autistic" and "non-autistic". To falsify this theory it would need to be shown that an objective characteristic can clearly separate both groups. For example, a genetic test that can fully substitute for a psychiatric diagnosis would undermine this theory.

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.

References

1. ^ Trottier G, Srivastava L, Walker CD (1999). "Etiology of infantile autism: a review of recent advances in genetic and neurobiological research". J Psychiatry Neurosci. 24 (2): 103–115. PMID 10212552. Retrieved 2007-07-16.{{cite journal}}: CS1 maint: multiple names: authors list (link)
2. ^ Freitag CM (2007). "The genetics of autistic disorders and its clinical relevance: a review of the literature". Mol Psychiatry. 12 (1): 2–22. doi:10.1038/sj.mp.4001896. PMID 17033636.
3. ^ Arndt TL, Stodgell CJ, Rodier PM (2005). "The teratology of autism". Int J Dev Neurosci. 23 (2–3): 189–99. doi:10.1016/j.ijdevneu.2004.11.001. PMID 15749245.{{cite journal}}: CS1 maint: multiple names: authors list (link)
4. ^ Rutter M (2005). "Incidence of autism spectrum disorders: changes over time and their meaning". Acta Paediatr. 94 (1): 2–15. doi:10.1080/08035250410023124. PMID 15858952.
5. American Psychiatric Association (2000). "Diagnostic criteria for 299.00 Autistic Disorder". Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision (DSM-IV-TR) ed.). ISBN 0890420254. {{cite book}}: |access-date= requires |url= (help); External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
6. World Health Organization (2006). "F84. Pervasive developmental disorders". International Statistical Classification of Diseases and Related Health Problems (10th ed. (ICD-10) ed.). {{cite book}}: |access-date= requires |url= (help); External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
7. ^ Happé F, Ronald A (2008). "The 'fractionable autism triad': a review of evidence from behavioural, genetic, cognitive and neural research". Neuropsychol Rev. doi:10.1007/s11065-008-9076-8. PMID 18956240.
8. ^ Happé F, Ronald A, Plomin R (2006). "Time to give up on a single explanation for autism". Nat Neurosci. 9 (10): 1218–20. doi:10.1038/nn1770. PMID 17001340.{{cite journal}}: CS1 maint: multiple names: authors list (link)
9. Mandy WP, Skuse DH (2008). "What is the association between the social-communication element of autism and repetitive interests, behaviours and activities?". J Child Psychol Psychiatry. doi:10.1111/j.1469-7610.2008.01911.x. PMID 18564070.
10. ^ Newschaffer CJ, Croen LA, Daniels J; et al. (2007). "The epidemiology of autism spectrum disorders". Annu Rev Public Health. 28: 235–58. doi:10.1146/annurev.publhealth.28.021406.144007. PMID 17367287. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
11. ^ Szpir M (2006). "Tracing the origins of autism: a spectrum of new studies". Environ Health Perspect. 114 (7): A412–8. PMID 16835042.
12. ^ Christison GW, Ivany K (2006). "Elimination diets in autism spectrum disorders: any wheat amidst the chaff?". J Dev Behav Pediatr. 27 (2 Suppl 2): S162–71. doi:10.1097/00004703-200604002-00015. PMID 16685183.
13. ^ Doja A, Roberts W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–6. PMID 17168158.
14. Taylor B (2006). "Vaccines and the changing epidemiology of autism". Child Care Health Dev. 32 (5): 511–9. doi:10.1111/j.1365-2214.2006.00655.x. PMID 16919130.
15. "NIH funds new program to investigate causes and treatment of autism" (Press release). National Institutes of Health. 2007-08-02. Retrieved 2007-08-03.
16. ^ Sykes NH, Lamb JA (2007). "Autism: the quest for the genes". Expert Rev Mol Med. 9 (24): 1–15. doi:10.1017/S1462399407000452. PMID 17764594.
17. Folstein SE, Rosen-Sheidley B (2001). "Genetics of autism: complex aetiology for a heterogeneous disorder". Nat Rev Genet. 2 (12): 943–55. doi:10.1038/35103559. PMID 11733747.
18. Persico AM, Bourgeron T (2006). "Searching for ways out of the autism maze: genetic, epigenetic and environmental clues". Trends Neurosci. 29 (7): 349–58. doi:10.1016/j.tins.2006.05.010. PMID 16808981.
19. Beaudet AL (2007). "Autism: highly heritable but not inherited". Nat Med. 13 (5): 534–6. doi:10.1038/nm0507-534. PMID 17479094.
20. Crespi B, Badcock C (2008). "Psychosis and autism as diametrical disorders of the social brain". Behav Brain Sci. 31 (3): 241–61. doi:10.1017/S0140525X08004214. PMID 18578904.
21. ^ Kolevzon A, Gross R, Reichenberg A (2007). "Prenatal and perinatal risk factors for autism". Arch Pediatr Adolesc Med. 161 (4): 326–33. doi:10.1001/archpedi.161.4.326. PMID 17404128.{{cite journal}}: CS1 maint: multiple names: authors list (link)
22. Patterson PH (2008). "Immune involvement in schizophrenia and autism: etiology, pathology and animal models". Behav Brain Res. doi:10.1016/j.bbr.2008.12.016. PMID 19136031.
23. Mendelsohn NJ, Schaefer GB (2008). "Genetic evaluation of autism". Semin Pediatr Neurol. 15 (1): 27–31. doi:10.1016/j.spen.2008.01.005. PMID 18342258.
24. Meyer U, Yee BK, Feldon J (2007). "The neurodevelopmental impact of prenatal infections at different times of pregnancy: the earlier the worse?". Neuroscientist. 13 (3): 241–56. doi:10.1177/1073858406296401. PMID 17519367.{{cite journal}}: CS1 maint: multiple names: authors list (link)
25. Dalton P, Deacon R, Blamire A; et al. (2003). "Maternal neuronal antibodies associated with autism and a language disorder". Ann Neurol. 53 (4): 533–7. doi:10.1002/ana.10557. PMID 12666123. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
26. Braunschweig D, Ashwood P, Krakowiak P; et al. (2008). "Autism: maternally derived antibodies specific for fetal brain proteins". Neurotoxicology. 29 (2): 226–31. doi:10.1016/j.neuro.2007.10.010. PMC 2305723. PMID 18078998. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
27. Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG (2008). "Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism". Brain Behav Immun. doi:10.1016/j.bbi.2007.12.007. PMID 18262386. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
28. Fombonne E (2002). "Is exposure to alcohol during pregnancy a risk factor for autism?". J Autism Dev Disord. 32 (3): 243. doi:10.1023/A:1015466100838. PMID 12108626.
29. Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C (2007). "Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley". Environ Health Perspect. 115 (10): 1482–9. doi:10.1289/ehp.10168. PMID 17938740. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
30. Singh ND, Sharma AK, Dwivedi P, Patil RD, Kumar M (2007). "Citrinin and endosulfan induced teratogenic effects in Wistar rats". J Appl Toxicol. 27 (2): 143–51. doi:10.1002/jat.1185. PMID 17186572.{{cite journal}}: CS1 maint: multiple names: authors list (link)
31. D'Amelio M, Ricci I, Sacco R; et al. (2005). "Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions". Mol Psychiatry. 10 (11): 1006–16. doi:10.1038/sj.mp.4001714. PMID 16027737. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
32. Karr CJ, Solomon GM, Brock-Utne AC (2007). "Health effects of common home, lawn, and garden pesticides". Pediatr Clin North Am. 54 (1): 63–80. doi:10.1016/j.pcl.2006.11.005. PMID 17306684.{{cite journal}}: CS1 maint: multiple names: authors list (link)
33. Román GC (2007). "Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents". J Neurol Sci. 262 (1–2): 15–26. doi:10.1016/j.jns.2007.06.023. PMID 17651757.
34. Muskiet FA, Kemperman RF (2006). "Folate and long-chain polyunsaturated fatty acids in psychiatric disease". J Nutr Biochem. 17 (11): 717–27. doi:10.1016/j.jnutbio.2006.02.001. PMID 16650750.
35. Kinney DK, Munir KM, Crowley DJ, Miller AM (2008). "Prenatal stress and risk for autism". Neurosci Biobehav Rev. 32 (8): 1519–32. doi:10.1016/j.neubiorev.2008.06.004. PMID 18598714.{{cite journal}}: CS1 maint: multiple names: authors list (link)
36. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G (2009). "Fetal testosterone and autistic traits". Br J Psychol. 100 (1): 1–22. doi:10.1348/000712608X311731. PMID 18547459. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
37. Manson JE (2008). "Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes". Metabolism. 57 (Suppl 2): S16–21. doi:10.1016/j.metabol.2008.07.010. PMID 18803959.
38. Rivers C (2006-09-28). "Discrimination against the female brain". AlterNet. Retrieved 2006-12-10.
39. Ang ES Jr, Gluncic V, Duque A, Schafer ME, Rakic P (2006). "Prenatal exposure to ultrasound waves impacts neuronal migration in mice". Proc Natl Acad Sci U S A. 103 (34): 12903–10. doi:10.1073/pnas.0605294103. PMC 1538990. PMID 16901978.{{cite journal}}: CS1 maint: multiple names: authors list (link)
40. Caviness VS, Grant PE (2006). "Our unborn children at risk?". Proc Natl Acad Sci U S A. 103 (34): 12661–2. doi:10.1073/pnas.0605505103. PMC 1568904. PMID 16912111.
41. Abramowicz JS (2007). "Prenatal exposure to ultrasound waves: is there a risk?". Ultrasound Obstet Gynecol. 29 (4): 363–7. doi:10.1002/uog.3983. PMID 17352453.
42. Limperopoulos C, Bassan H, Gauvreau K; et al. (2007). "Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?". Pediatrics. 120 (3): 584–93. doi:10.1542/peds.2007-1041. PMID 17766532. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
43. Ashwood P, Van de Water J (2004). "Is autism an autoimmune disease?". Autoimmun Rev. 3 (7–8): 557–62. doi:10.1016/j.autrev.2004.07.036. PMID 15546805.
44. Ashwood P, Wills S, Van de Water J (2006). "The immune response in autism: a new frontier for autism research". J Leukoc Biol. 80 (1): 1–15. doi:10.1189/jlb.1205707. PMID 16698940.{{cite journal}}: CS1 maint: multiple names: authors list (link)
45. Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J (2007). "Autoantibodies in autism spectrum disorders (ASD)". Ann N Y Acad Sci. 1107: 79–91. doi:10.1196/annals.1381.009. PMID 17804535.{{cite journal}}: CS1 maint: multiple names: authors list (link)
46. Schmitz C, Rezaie P (2008). "The neuropathology of autism: where do we stand?". Neuropathol Appl Neurobiol. 34 (1): 4–11. doi:10.1111/j.1365-2990.2007.00872.x. PMID 17971078.
47. ^ Johnson TW (2006). "Dietary considerations in autism: identifying a reasonable approach". Top Clin Nutr. 21 (3): 212–25.
48. ^ Wakefield A, Murch S, Anthony A; et al. (1998). "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children". Lancet. 351 (9103): 637–41. doi:10.1016/S0140-6736(97)11096-0. PMID 9500320. Retrieved 2007-09-05. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
49. MacDonald TT, Domizio P (2007). "Autistic enterocolitis; is it a histopathological entity?". Histopathology. 50 (3): 371–9. doi:10.1111/j.1365-2559.2007.02606.x. PMID 17257133.
50. ^ Deer B (2009-02-08). "MMR doctor Andrew Wakefield fixed data on autism". Sunday Times. Retrieved 2009-02-09.
51. Horvath K, Stefanatos G, Sokolski KN, Wachtel R, Nabors L, Tildon JT (1998). "Improved social and language skills after secretin administration in patients with autistic spectrum disorders". J Assoc Acad Minor Phys. 9 (1): 9–15. PMID 9585670.{{cite journal}}: CS1 maint: multiple names: authors list (link)
52. Sturmey P (2005). "Secretin is an ineffective treatment for pervasive developmental disabilities: a review of 15 double-blind randomized controlled trials". Res Dev Disabil. 26 (1): 87–97. doi:10.1016/j.ridd.2004.09.002. PMID 15590241.
53. Cass H, Gringras P, March J; et al. (2008). "Absence of urinary opioid peptides in children with autism". Arch Dis Child. doi:10.1136/adc.2006.114389. PMID 18337276. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
54. Libbey JE, Sweeten TL, McMahon WM, Fujinami RS (2005). "Autistic disorder and viral infections". J Neurovirol. 11 (1): 1–10. doi:10.1080/13550280590900553. PMID 15804954.{{cite journal}}: CS1 maint: multiple names: authors list (link)
55. Becker KG (2007). "Autism, asthma, inflammation, and the hygiene hypothesis". Med Hypotheses. 69 (4): 731–40. doi:10.1016/j.mehy.2007.02.019. PMID 17412520.
56. Ng F, Berk M, Dean O, Bush AI (2008). "Oxidative stress in psychiatric disorders: evidence base and therapeutic implications". Int J Neuropsychopharmacol. doi:10.1017/S1461145707008401. PMID 18205981.{{cite journal}}: CS1 maint: multiple names: authors list (link)
57. Kern JK, Jones AM (2006). "Evidence of toxicity, oxidative stress, and neuronal insult in autism". J Toxicol Environ Health B Crit Rev. 9 (6): 485–99. doi:10.1080/10937400600882079. PMID 17090484.
58. Schultz RT (2005). "Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area". Int J Dev Neurosci. 23 (2–3): 125–41. doi:10.1016/j.ijdevneu.2004.12.012. PMID 15749240.
59. Cannell JJ (2007). "Autism and vitamin D". Med Hypotheses. PMID 17920208.
60. Zafeiriou DI, Ververi A, Vargiami E (2007). "Childhood autism and associated comorbidities". Brain Dev. 29 (5): 257–72. doi:10.1016/j.braindev.2006.09.003. PMID 17084999.{{cite journal}}: CS1 maint: multiple names: authors list (link)
61. Austin D (2008). "An epidemiological analysis of the 'autism as mercury poisoning' hypothesis". Int J Risk Saf Med. 20 (3): 135–42. doi:10.3233/JRS-2008-0436.
62. Davidson PW, Myers GJ, Weiss B (2004). "Mercury exposure and child development outcomes". Pediatrics. 113 (4 Suppl): 1023–9. doi:10.1542/peds.113.4.S1.1023. PMID 15060195.{{cite journal}}: CS1 maint: multiple names: authors list (link)
63. Weber W, Newmark S (2007). "Complementary and alternative medical therapies for attention-deficit/hyperactivity disorder and autism". Pediatr Clin North Am. 54 (6): 983–1006. doi:10.1016/j.pcl.2007.09.006. PMID 18061787.
64. Holmes AS, Blaxill MF, Haley BE (2003). "Reduced levels of mercury in first baby haircuts of autistic children". Int J Toxicol. 22 (4): 277–85. doi:10.1080/10915810305120. PMID 12933322.{{cite journal}}: CS1 maint: multiple names: authors list (link)
65. Ng DK, Chan CH, Soo MT, Lee RS (2007). "Low-level chronic mercury exposure in children and adolescents: meta-analysis". Pediatr Int. 49 (1): 80–7. doi:10.1111/j.1442-200X.2007.02303.x. PMID 17250511.{{cite journal}}: CS1 maint: multiple names: authors list (link)
66. Palmer RF, Blanchard S, Stein Z, Mandell D, Miller C (2006). "Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas". Health Place. 12 (2): 203–9. doi:10.1016/j.healthplace.2004.11.005. PMID 16338635.{{cite journal}}: CS1 maint: multiple names: authors list (link)
67. Palmer RF, Blanchard S, Wood R (2009). "Proximity to point sources of environmental mercury release as a predictor of autism prevalence". Health Place. 15 (1): 18–24. doi:10.1016/j.healthplace.2008.02.001. PMID 18353703. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
68. "MMR the facts". NHS. Retrieved 2007-07-29.
69. Murch SH, Anthony A, Casson DH; et al. (2004). "Retraction of an interpretation". Lancet. 363 (9411): 750. doi:10.1016/S0140-6736(04)15715-2. PMID 15016483. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
70. Deer B (2008-11-02). "The MMR-autism crisis - our story so far". Retrieved 2008-12-06.
71. "Measles, mumps, and rubella (MMR) vaccine". Centers for Disease Control and Prevention. 2008-12-23. Retrieved 2009-02-14.
72. "Immunization safety review: vaccines and autism". Institute of Medicine, National Academy of Sciences. 2004. Retrieved 2007-06-13.
73. "MMR the facts". National Health Service. Retrieved 2007-06-13.
74. "MMR scare doctor 'paid children'". BBC News. 2007-07-16. Retrieved 2007-07-29.
75. Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M (2008). "Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey". Autism. 12 (3): 293–307. doi:10.1177/1362361307089518. PMID 18445737.{{cite journal}}: CS1 maint: multiple names: authors list (link)
76. Waldman M, Nicholson S, Adilov N, Williams J (2008). "Autism prevalence and precipitation rates in California, Oregon, and Washington counties". Arch Pediatr Adolesc Med. 162 (11): 1026–34. doi:10.1001/archpedi.162.11.1026. PMID 18981350. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
77. Weiss NS (2008). "Precipitation and autism: do these results warrant publication?". Arch Pediatr Adolesc Med. 162 (11): 1095–6. doi:10.1001/archpedi.162.11.1095. PMID 18981361.
78. Waldman M, Nicholson S, Adliov N (2006). "Does television cause autism?". Johnson School Research Paper Series No. 01-07. Retrieved 2007-07-27. {{cite journal}}: Cite journal requires |journal= (help)CS1 maint: multiple names: authors list (link)
79. Wallis C (2006-10-20). "Does watching TV cause autism?". TIME. Retrieved 2007-07-28.
80. Guidotti T (2005). "Evidence of causation". Arch Environ Occup Health. 60 (6): 283–4. doi:10.3200/AEOH.60.6.283-286. PMID 17447569.
81. Bettelheim B (1967). The Empty Fortress: Infantile Autism and the Birth of the Self. Free Press. ISBN 0029031400.
82. Kanner L (1943). "Autistic disturbances of affective contact". Nerv Child. 2: 217–50. "Reprint". Acta Paedopsychiatr. 35 (4): 100–36. 1968. PMID 4880460. {{cite journal}}: Unknown parameter |quotes= ignored (help)
83. Kanner L (1949). "Problems of nosology and psychodynamics in early childhood autism". Am J Orthopsychiatry. 19 (3): 416–26. PMID 18146742.
84. Gardner M (2000). "The brutality of Dr. Bettelheim". Skeptical Inquirer. 24 (6): 12–4.
85. Rutter ML, Kreppner JM, O'Connor TG, English and Romanian Adoptees (ERA) study team (2001). "Specificity and heterogeneity in children's responses to profound institutional privation". Br J Psychiatry. 179 (2): 97–103. doi:10.1192/bjp.179.2.97. PMID 11483469.{{cite journal}}: CS1 maint: multiple names: authors list (link)
86. Hoksbergen R, ter Laak J, Rijk K, van Dijkum C, Stoutjesdijk F (2005). "Post-Institutional Autistic Syndrome in Romanian adoptees". J Autism Dev Disord. 35 (5): 615–23. doi:10.1007/s10803-005-0005-x. PMID 16167089.{{cite journal}}: CS1 maint: multiple names: authors list (link)
87. Gomberoff M, De Gomberoff LP (2000). "Autistic devices in small children in mourning". Int J Psychoanal. 81 (5): 907–20. PMID 11109576.
88. Timimi S, Taylor E (2004). "ADHD is best understood as a cultural construct". Br J Psychiatry. 184: 8–9. doi:10.1192/bjp.184.1.8. PMID 14702221.
89. Timimi S (2004). "Diagnosis of autism: current epidemic has social context". BMJ. 328 (7433): 226. doi:10.1136/bmj.328.7433.226-a. PMID 14739199.
90. Hacking I (1999). The Social Construction of What?. Harvard University Press. pp. 114–23. ISBN 0674004124.
91. "Does autism exist?". Natural Variation – Autism Blog. 2006-02-24. Retrieved 2007-07-29.
92. Nadesan MH (2005). "The dialectics of autism: theorizing autism, performing autism, remediating autism, and resisting autism". Constructing Autism: Unravelling the 'Truth' and Understanding the Social. Routledge. pp. 179–213. ISBN 0415321816.

• Autism