This article duplicates the scope of other articles, specifically Pathophysiology of autism.(June 2023) |
It has been suggested that this article be merged with Pathophysiology of autism . (Discuss) Proposed since June 2023. |
The mechanisms of autism are the molecular and cellular processes believed to cause or contribute to the symptoms of autism. Multiple processes are hypothesized to explain different autism spectrum features. These hypotheses include defects in synapse structure and function, [1] [2] reduced synaptic plasticity, [3] disrupted neural circuit function, gut–brain axis dyshomeostasis, [4] [5] [6] neuroinflammation, [7] and altered brain structure or connectivity. [8] [9] [10] [11]
Unlike some brain disorders which have clear molecular hallmarks that can be observed in every affected individual, such as Alzheimer's disease or Parkinson's disease, autism does not have a unifying mechanism at the molecular, cellular, or systems level. The autism spectrum may comprise a small set of disorders that converge on a few common molecular pathways, or it may be a large set of disorders with diverse mechanisms. [13] Autism appears to result from developmental factors that affect many or all functional brain systems. [14] Some factors may disturb the timing of brain development rather than the final product. [12]
Neuroanatomical studies and the association between autism and teratogens strongly suggest that autism affects brain development soon after conception. [15] This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors. [16] Just after birth, the brains of children with autism tend to grow faster than usual, followed by normal or relatively slower growth in childhood. [17] It is unknown whether early brain overgrowth occurs in all children with autism. It appears to be most prominent in the frontal and temporal lobes, which are associated with higher cognitive specializations such as social cognition, and language development. [18] Hypotheses for the cellular and molecular bases of pathological early overgrowth include an excess of neurons that causes local overconnectivity in key brain regions, [17] and disturbed neuronal migration during early gestation. [19] [20]
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Synapse and dendritic spine growth may be disrupted in autism due to impaired neurexin–neuroligin cell-adhesion signaling [21] or dysregulated synthesis of synaptic proteins. [22] [23] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated. [24] Studies have suggested that excitatory–inhibitory networks may be imbalanced in autism. [20]
Neurotransmitters such as serotonin, dopamine, and glutamate have been implicated in autism. [1] Fragile X, the most common genetic cause of autism, is linked to dysfunction of group I metabotropic glutamate receptors (mGluR), leading some to consider their potential role in autism. [25]
The underconnectivity theory of autism posits that autistic people tend to have fewer high-level neural connections and less global synchronization, along with an excess of low-level processes. [27] Functional connectivity studies have found both hypo- and hyperconnectivity in brains of autistic people. [28] Hypoconnectivity is commonly observed for interhemispheric and cortico-cortical functional connectivity. [29] Some studies have found local overconnectivity in the cerebral cortex and weak functional connections between the frontal lobe and the rest of the cortex. [30] Abnormal default mode network (task-negative) connectivity is often observed. Toggling between task-negative network activation and task-positive network activation (consisting of the dorsal attention network and salience network) may be less efficient, possibly reflecting a disturbance of self-referential thought. [31] Such patterns of low function and aberrant activation in the brain may depend on whether the brain is performing social or nonsocial tasks. [32]
Some studies have suggested that autism is a disorder of the association cortex. [33] Event-related potentials with respect to attention, orientation to auditory and visual stimuli, novelty detection, language and face processing, and information storage are altered in autistic individuals; several studies have found a preference for nonsocial stimuli. [34] Magnetoencephalography studies have observed delayed processing of auditory signals in autistic children. [35]
The mirror neuron system (MNS) theory of autism hypothesizes that disrupted development of the MNS impairs autistic people's ability to imitate others, leading to core autistic features of social impairment and communication difficulties. In animals, the MNS activates when an animal performs an action or observes another animal perform the same action. The MNS may contribute to an individual's understanding of other people by enabling the modeling of their behavior via embodied simulation of their actions, intentions, and emotions. [36] [37] Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with ASD, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD. [38] However, individuals with autism also have abnormal brain activation in many circuits outside the MNS [39] and the MNS theory does not explain the normal performance of children with autism on imitation tasks that involve a goal or object. [40]
Common copy number variation associations have suggested similarities between the mechanisms of autism and schizophrenia. For loci such as 16p11.2, 16p13.1, 22p11, and 22q13, deletion is associated with autism whereas duplication is associated with schizophrenia. Conversely, 1q21.1 and 22p11.2 duplication is associated with autism and deletion with schizophrenia. [41]
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The immune system is thought to play an important role in autism. Children with autism have been found by researchers to have inflammation of both the peripheral and central immune systems as indicated by increased levels of pro-inflammatory cytokines and significant activation of microglia. [42] [43] [7] Biomarkers of abnormal immune function have also been associated with increased impairments in behaviors that are characteristic of the core features of autism such as, deficits in social interactions and communication. [43] Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. It is thought that activation of a pregnant mother's immune system such as from environmental toxicants or infection can contribute to causing autism through causing a disruption of brain development. [44] [45] [46] This is supported by recent studies that have found that infection during pregnancy is associated with an increased risk of autism. [47] [48]
Some evidence suggests that gut–brain axis abnormalities may be involved by means of impaired serotonin signaling and inflammation. [6] A 2015 review proposed that immune dysregulation, gastrointestinal inflammation, autonomic nervous system malfunction, gut microbiota alterations, and food metabolites may cause brain neuroinflammation and dysfunction. [4] A 2016 review concluded that enteric nervous system abnormalities might play a role in neurological disorders such as autism. [5]
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Some data suggests neuronal overgrowth observed in autism may be caused by an increase in several growth hormones [49] or impaired regulation of growth factor receptors. Some inborn errors of metabolism are associated with autism, but probably account for less than 5% of cases. [50]
Two major categories of cognitive theories have been proposed to explain links between autistic brains and behavior.
The first category focuses on deficits in social cognition. Simon Baron-Cohen's empathizing–systemizing theory postulates that autistic individuals can systemize—that is, they can develop internal rules of operation to handle events inside the brain—but are less effective at empathizing by handling events generated by other agents. An extension, the extreme male brain theory, hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing. [51] These theories are somewhat related to Baron-Cohen's earlier theory of mind approach, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others. The theory of mind hypothesis is supported by the atypical responses of children with autism to the Sally–Anne test for reasoning about others' motivations, [51] and the mirror neuron system theory of autism described in Pathophysiology maps well to the hypothesis. [38] However, most studies have found no evidence of impairment in autistic individuals' ability to understand other people's basic intentions or goals; instead, data suggests that impairments are found in understanding more complex social emotions or in considering others' viewpoints. [52]
The second category focuses on nonsocial or general processing: the executive functions such as working memory, planning, inhibition. In his review, Kenworthy states that "the claim of executive dysfunction as a causal factor in autism is controversial", however, "it is clear that executive dysfunction plays a role in the social and cognitive deficits observed in individuals with autism". [53] Tests of core executive processes such as eye movement tasks indicate improvement from late childhood to adolescence, but performance never reaches typical adult levels. [54] A strength of the theory is predicting stereotyped behavior and narrow interests; [55] two weaknesses are that executive function is hard to measure [53] and that executive function deficits have not been found in young children with autism. [56]
Weak central coherence theory hypothesizes that a limited ability to see the big picture underlies the central disturbance in autism. One strength of this theory is predicting special talents and peaks in performance in autistic people. [57] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals. [58] Yet another, monotropism, posits that autism stems from a different cognitive style, tending to focus attention (or processing resources) intensely, to the exclusion of other stimuli. [59] These theories map well from the underconnectivity theory of autism.
Neither category is satisfactory on its own; social cognition theories poorly address autism's rigid and repetitive behaviors, while most of the nonsocial theories have difficulty explaining social impairment and communication difficulties. [60] A combined theory based on multiple deficits may prove to be more useful. [61]
Asperger syndrome (AS), also known as Asperger's syndrome, formerly described a neurodevelopmental disorder characterized by significant difficulties in social interaction and nonverbal communication combined with restricted and repetitive patterns of behavior and interests. The syndrome has been merged with other disorders into autism spectrum disorder (ASD) and is no longer considered a stand-alone diagnosis. It was considered to differ from other diagnoses that were merged into ASD by relatively unimpaired spoken language and intelligence.
In psychology, theory of mind refers to the capacity to understand other people by ascribing mental states to them. A theory of mind includes the knowledge that others' beliefs, desires, intentions, emotions, and thoughts may be different from one's own. Possessing a functional theory of mind is crucial for success in everyday human social interactions. People utilise a theory of mind when analyzing, judging, and inferring others' behaviors. The discovery and development of theory of mind primarily came from studies done with animals and infants. Factors including drug and alcohol consumption, language development, cognitive delays, age, and culture can affect a person's capacity to display theory of mind. Having a theory of mind is similar to but not identical with having the capacity for empathy or sympathy.
Diagnoses of autism have become more frequent since the 1980s, which has led to various controversies about both the cause of autism and the nature of the diagnoses themselves. Whether autism has mainly a genetic or developmental cause, and the degree of coincidence between autism and intellectual disability, are all matters of current scientific controversy as well as inquiry. There is also more sociopolitical debate as to whether autism should be considered a disability on its own.
Autism spectrum disorders (ASD) are neurodevelopmental disorders that begin in early childhood, persist throughout adulthood, and affect three crucial areas of development: communication, social interaction and restricted patterns of behavior. There are many conditions comorbid to autism spectrum disorders such as attention-deficit hyperactivity disorder and epilepsy.
A mirror neuron is a neuron that fires both when an organism acts and when the organism observes the same action performed by another. Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting. Mirror neurons are not always physiologically distinct from other types of neurons in the brain; their main differentiating factor is their response patterns. By this definition, such neurons have been directly observed in humans and primate species, and in birds.
Mind-blindness, mindblindness or mind blindness is a theory initially proposed in 1990 that claims that all autistic people have a lack or developmental delay of theory of mind (ToM), meaning they are unable to attribute mental states to others. According to the theory, a lack of ToM is considered equivalent to a lack of both cognitive and affective empathy. In the context of the theory, mind-blindness implies being unable to predict behavior and attribute mental states including beliefs, desires, emotions, or intentions of other people. The mind-blindness theory asserts that children who delay in this development will often develop autism.
The causes of autism are environmental or genetic factors that predispose an individual to develop autism, also known as autism spectrum disorder (ASD). Many causes of autism have been proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction and restricted/repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals.
The sensorimotor mu rhythm, also known as mu wave, comb or wicket rhythms or arciform rhythms, are synchronized patterns of electrical activity involving large numbers of neurons, probably of the pyramidal type, in the part of the brain that controls voluntary movement. These patterns as measured by electroencephalography (EEG), magnetoencephalography (MEG), or electrocorticography (ECoG), repeat at a frequency of 7.5–12.5 Hz, and are most prominent when the body is physically at rest. Unlike the alpha wave, which occurs at a similar frequency over the resting visual cortex at the back of the scalp, the mu rhythm is found over the motor cortex, in a band approximately from ear to ear. People suppress mu rhythms when they perform motor actions or, with practice, when they visualize performing motor actions. This suppression is called desynchronization of the wave because EEG wave forms are caused by large numbers of neurons firing in synchrony. The mu rhythm is even suppressed when one observes another person performing a motor action or an abstract motion with biological characteristics. Researchers such as V. S. Ramachandran and colleagues have suggested that this is a sign that the mirror neuron system is involved in mu rhythm suppression, although others disagree.
Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activity-dependent plasticity is a form of neuroplasticity that arises from intrinsic or endogenous activity, as opposed to forms of neuroplasticity that arise from extrinsic or exogenous factors, such as electrical brain stimulation- or drug-induced neuroplasticity. The brain's ability to remodel itself forms the basis of the brain's capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is associated with neural plasticity and therefore many of the functions individuals perform on a daily basis. This plasticity occurs as a result of changes in gene expression which are triggered by signaling cascades that are activated by various signaling molecules during increased neuronal activity.
In psychology and neuroscience, executive dysfunction, or executive function deficit, is a disruption to the efficacy of the executive functions, which is a group of cognitive processes that regulate, control, and manage other cognitive processes. Executive dysfunction can refer to both neurocognitive deficits and behavioural symptoms. It is implicated in numerous psychopathologies and mental disorders, as well as short-term and long-term changes in non-clinical executive control. Executive dysfunction is the mechanism underlying ADHD Paralysis, and in a broader context, it can encompass other cognitive difficulties like planning, organizing, initiating tasks and regulating emotions. It is a core characteristic of ADHD and can elucidate numerous other recognized symptoms.
Classic autism, also known as childhood autism, autistic disorder, (early) infantile autism, infantile psychosis, Kanner's autism,Kanner's syndrome, or (formerly) just autism, is a neurodevelopmental condition first described by Leo Kanner in 1943. It is characterized by atypical and impaired development in social interaction and communication as well as restricted, repetitive behaviors, activities, and interests. These symptoms first appear in early childhood and persist throughout life.
Autism, formally called autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder characterized by deficits in social communication and social interaction, and repetitive or restricted patterns of behaviors, interests, or activities, which can include hyper- and hyporeactivity to sensory input. Autism is clinically regarded as a spectrum disorder, meaning that it can manifest very differently in each person. For example, some are nonverbal, while others have proficient spoken language. Because of this, there is wide variation in the support needs of people across the autism spectrum.
The imprinted brain hypothesis is an unsubstantiated hypothesis in evolutionary psychology regarding the causes of autism spectrum and schizophrenia spectrum disorders, first presented by Bernard Crespi and Christopher Badcock in 2008. It claims that certain autistic and schizotypal traits are opposites, and that this implies the etiology of the two conditions must be at odds.
The evolution of schizophrenia refers to the theory of natural selection working in favor of selecting traits that are characteristic of the disorder. Positive symptoms are features that are not present in healthy individuals but appear as a result of the disease process. These include visual and/or auditory hallucinations, delusions, paranoia, and major thought disorders. Negative symptoms refer to features that are normally present but are reduced or absent as a result of the disease process, including social withdrawal, apathy, anhedonia, alogia, and behavioral perseveration. Cognitive symptoms of schizophrenia involve disturbances in executive functions, working memory impairment, and inability to sustain attention.
This relationship between autism and memory, specifically memory functions in relation to Autism Spectrum Disorder (ASD), has been an ongoing topic of research. ASD is a neurodevelopmental disorder characterised by social communication and interaction impairments, along with restricted and repetitive patterns of behavior. In this article, the word autism is used to refer to the whole range of conditions on the autism spectrum, which are not uncommon.
Paul Ashwood is an associate professor of immunology at the MIND Institute at the University of California Davis. His lab conducts research regarding the potential role of immune system disorders in autism, as well as other neurodevelopmental disorders such as Fragile X syndrome, Tourette syndrome, schizophrenia and mood disorders.
The development of an animal model of autism is one approach researchers use to study potential causes of autism. Given the complexity of autism and its etiology, researchers often focus only on single features of autism when using animal models.
Sex and gender differences in autism exist regarding prevalence, presentation, and diagnosis.
Autism is characterized by the early onset of impairments in reciprocal social interaction and communication and restricted repetitive behaviors or interests. One of the many hypotheses explaining the psychopathology of autism, the deficit in joint attention hypothesis is prominent in explaining the disorder's social and communicative deficits. Nonverbal autism is a subset of autism spectrum where the person does not learn how to speak. It is estimated that 25% to 50% of children diagnosed with autism spectrum never develop spoken language beyond a few words or utterances.
The pathophysiology of autism is the study of the physiological processes that cause or are otherwise associated with autism spectrum disorders.