A wide variety of postnatal contributors to autism have been proposed, including gastrointestinal or immune system abnormalities, allergies, and exposure of children to drugs, infection, certain foods, or heavy metals. The evidence for these risk factors is anecdotal and has not been confirmed by reliable studies.
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.
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 and the nervous system begin early during
embryogenesis, and successful neurodevelopment depends on a balanced immune response. It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of autism. A small percentage of autism cases are associated with infection, usually before birth. Results from immune studies have been contradictory. Some abnormalities have been found in specific subgroups, and some of these have been replicated. It is not known whether these abnormalities are relevant to the pathology of autism, for example, by infection or autoimmunity, or whether they are secondary to the disease processes. As
autoantibodies are found in diseases other than autism, and are not always present in autism, the relationship between immune disturbances and autism remains unclear and controversial. A 2015 systematic review and meta-analysis found that children with a family history of autoimmune diseases were at a greater risk of autism compared to children without such a history. When an underlying maternal autoimmune disease is present, antibodies circulating to the fetus could contribute to the development of autism spectrum disorders.
Gastrointestinal connection Gastrointestinal problems are one of the most commonly
associated medical disorders in people with autism. These are linked to greater social impairment, irritability, behavior and sleep problems, language impairments and mood changes, so the theory that they are an overlap syndrome has been postulated. Studies indicate that
gastrointestinal inflammation,
food allergies,
gluten-related disorders (
celiac disease,
wheat allergy,
non-celiac gluten sensitivity),
visceral hypersensitivity,
dysautonomia and
gastroesophageal reflux are the mechanisms that possibly link both. A 2018 review suggests that the frequent association of
gastrointestinal disorders and autism is due to abnormalities of the
gut–brain axis. It is based on the idea that defects in the
intestinal barrier produce an excessive increase in
intestinal permeability, allowing substances present in the intestine (including bacteria, environmental toxins, and food
antigens) to pass into the blood. The data supporting this theory are limited and contradictory, since both increased intestinal permeability and normal permeability have been documented in people with autism. Studies with mice provide some support to this theory and suggest the importance of
intestinal flora, demonstrating that the normalization of the intestinal barrier was associated with an improvement in some of the autism-like behaviors. This allows passage of bacterial
endotoxins from the gut into the bloodstream, stimulating liver cells to secrete
tumor necrosis factor alpha (TNFα), which modulates
blood–brain barrier permeability. Studies on ASD people showed that TNFα cascades produce proinflammatory cytokines, leading to peripheral inflammation and activation of microglia in the brain, which indicates
neuroinflammation. Later studies found secretin clearly ineffective in treating autism.
Endogenous opiate precursor theory In 1979, a possible association between autism and
opioids was proposed, it was noted that injecting small amounts of opiates into young laboratory animals resulted in symptoms similar to those seen in autistic children. The possibility of a relationship between autism and the consumption of
gluten and
casein was first articulated by
Kalle Reichelt in 1991. Opiate theory hypothesizes that autism is the result of a metabolic disorder in which opioid peptides
gliadorphin (aka gluteomorphin) and
Casomorphin, produced through metabolism of gluten (present in wheat and related cereals) and casein (present in dairy products), pass through an abnormally permeable intestinal wall and then proceed to exert an effect on neurotransmission through binding with opioid receptors. It has been postulated that the resulting excess of opioids affects brain maturation and causes autistic symptoms including
: behavioral difficulties, attention problems, and alterations in communicative capacity and social and cognitive functioning. Although high levels of these opioids are eliminated in the urine, it has been suggested that a small part of them cross into the brain causing interference of signal transmission and disruption of normal activity. Three studies have reported that urine samples of people with autism show an increased 24-hour peptide excretion. As of 2021, reliable studies have not demonstrated the benefit of gluten-free diets in the treatment of autism. In the subset of people who have
gluten sensitivity there is limited evidence that suggests that a gluten-free diet may improve some autistic behaviors. Although there have been many studies on the role of vitamin D in the development of autism, the majority of them are limited by their inability to assess the deficiency prior to an autism diagnosis.
Toxic exposure Multiple studies have attempted to study the relationship between toxic exposure and autism, despite limitations related to the measurement of toxic exposure the methods for which were often indirect and cross-sectional. Systematic reviews have been conducted for numerous toxins including air pollution, thimerosal, inorganic mercury, and levels of heavy metals in hair, nails, and bodily fluids. Significant evidence has not been found of an association between autism and the concentration of copper, cadmium, selenium, and chromium in the hair, nails, and bodily fluids.
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.
Oxidative stress Oxidative stress, oxidative
DNA damage and disruptions of
DNA repair have been postulated to play a role in the etiopathology of both ASD and schizophrenia. Physiological factors and mechanisms influence by oxidative stress are believed to be highly influential to autism risk. Interactions between environmental and genetic factors may increase oxidative stress in children with autism. This theory hypothesizes that toxicity and
oxidative stress may cause autism in some cases. Evidence includes genetic effects on metabolic pathways, reduced antioxidant capacity, enzyme changes, and enhanced biomarkers for oxidative stress. Polymorphism of genes involved metabolization of glutathione is evidenced by lower levels of total glutathione, and higher levels of oxidized glutathione in autistic children. Based on this theory,
antioxidants may be a useful treatment for autism. Environmental factors can influence oxidative stress pre, peri, and postnatally and include heavy metals, infection, certain drugs, and toxic exposure from various sources including cigarette smoke, air pollutants, and
organophosphate pesticides. It has been theorized that perceptions towards the characteristics of autistic individuals have been heavily influenced by neurotypical ideologies and social norms. Mild and moderate variations of autism are particular targets of the theory that social factors determine what it means to be autistic. The theory hypothesizes that individuals with these diagnoses inhabit the identities that have been ascribed to them, and promote their sense of well-being by resisting or appropriating autistic ascriptions. Lynn Waterhouse suggests that autism has been reified, in that social processes have endowed it with more reality than is justified by the scientific evidence. Although social construction of the autistic identity can have a positive impact on the well-being and treatment of autistic individuals, that is not always the case when the individuals in question belong to historically marginalized populations.
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. ==Evolutionary explanations==