This is currently being
merged. After a discussion, consensus to merge this into Mechanism of autism was found. You can help implement the merge by following the instructions at Help:Merging and the resolution on the discussion. Process started in June 2023. |
The pathophysiology of autism is the study of the physiological processes that cause or are otherwise associated with autism spectrum disorders.
Autism's symptoms result from maturation-related changes in various systems of the brain. [1] How autism occurs is not yet well understood. Its mechanism can be divided into two areas: the pathophysiology of brain structures and processes associated with autism, and the neuropsychological linkages between brain structures and behaviors. [1] The behaviors appear to have multiple pathophysiologies. [2]
There is evidence that gut–brain axis abnormalities may be involved. [3] [4] [5] A 2015 review proposed that immune, gastrointestinal inflammation, malfunction of the autonomic nervous system, gut flora alterations, and food metabolites may cause brain neuroinflammation and dysfunction. [4] A 2016 review concludes that enteric nervous system abnormalities might play a role in neurological disorders such as autism. Neural connections and the immune system are a pathway that may allow diseases originated in the intestine spread to the brain. [5]
Several lines of evidence point to synaptic dysfunction as a cause of autism. [6] Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion. [7] All known teratogens (agents that cause birth defects) related to the risk of autism 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, there is strong evidence that autism arises very early in development. [8]
In general, neuroanatomical studies support the concept that autism may involve a combination of brain enlargement in some areas and reduction in others. [9] These studies suggest that autism may be caused by abnormal neuronal growth and pruning during the early stages of prenatal and postnatal brain development, leaving some areas of the brain with too many neurons and other areas with too few neurons. [10] Some research has reported an overall brain enlargement in autism, while others suggest abnormalities in several areas of the brain, including the frontal lobe, the mirror neuron system, the limbic system, the temporal lobe, and the corpus callosum. [11] [12]
In functional neuroimaging studies, when performing theory of mind and facial emotion response tasks, the median person on the autism spectrum exhibits less activation in the primary and secondary somatosensory cortices of the brain than the median member of a properly sampled control population. This finding coincides with reports demonstrating abnormal patterns of cortical thickness and grey matter volume in those regions of autistic peoples' brains. [13]
The imbalance in excitatory and inhibitory neurotransmission, particularly involving neurotransmitters such as glutamate and gamma-aminobutyric acid, has also been proposed as a potential mechanism underlying the behavioral and cognitive manifestations observed in individuals with ASD. [14]
Brains of autistic individuals have been observed to have abnormal connectivity and the degree of these abnormalities directly correlates with the severity of autism. Following are some observed abnormal connectivity patterns in autistic individuals: [15] [16]
Listed below are some characteristic findings in ASD brains on molecular and cellular levels regardless of the specific genetic variation or mutation contributing to autism in a particular individual:
46% to 84% of autistic individuals have GI-related problems like reflux, diarrhea, constipation, inflammatory bowel disease, and food allergies. [18] It has been observed that the makeup of gut bacteria in autistic people is different than that of neurotypical individuals which has raised the question of influence of gut bacteria on ASD development via inducing an inflammatory state. [19] Listed below are some research findings on the influence of gut bacteria and abnormal immune responses on brain development: [19]
A number of discrete brain regions and networks among regions that are involved in dealing with other people have been discussed together under the rubric of the social brain. As of 2012 [update], there is a consensus that autism spectrum is likely related to problems with interconnectivity among these regions and networks, rather than problems with any specific region or network. [20]
Functions of the temporal lobe are related to many of the deficits observed in individuals with ASDs, such as receptive language, social cognition, joint attention, action observation, and empathy. The temporal lobe also contains the superior temporal sulcus and the fusiform face area, which may mediate facial processing. It has been argued that dysfunction in the superior temporal sulcus underlies the social deficits that characterize autism. Compared to neurotypical individuals, one study found that individuals with high-functioning autism had reduced activity in the fusiform face area when viewing pictures of faces. [21][ verification needed]
ASD could be linked to mitochondrial disease, a basic cellular abnormality with the potential to cause disturbances in a wide range of body systems. [22] A 2012 meta-analysis study, as well as other population studies show that approximately 5% of autistic children meet the criteria for classical mitochondrial dysfunction. [23] It is unclear why this mitochondrial disease occurs, considering that only 23% of children with both ASD and mitochondrial disease present with mitochondrial DNA abnormalities. [23]
Serotonin is a major neurotransmitter in the nervous system and contributes to formation of new neurons ( neurogenesis), formation of new connections between neurons ( synaptogenesis), remodeling of synapses, and survival and migration of neurons, processes that are necessary for a developing brain and some also necessary for learning in the adult brain. 45% of ASD individuals have been found to have increased blood serotonin levels. [16] Abnormalities in the serotonin transporter have also been found in ASD individuals. It has been hypothesized that increased activity of serotonin in the developing brain may facilitate the onset of ASD, with an association found in six out of eight studies between the use of selective serotonin reuptake inhibitors (SSRIs) by the pregnant mother and the development of ASD in the child exposed to SSRI in the antenatal environment. [24]
The study could not definitively conclude SSRIs caused the increased risk for ASD due to the biases found in those studies, and the authors called for more definitive, better conducted studies. [25] Confounding by indication has since then been shown to be likely. [26] However, it is also hypothesized that SSRIs may help reduce symptoms of ASD and even positively affect brain development in some ASD patients. [16]
immune dysregulation, GI inflammation, malfunction of the ANS, genetic and metabolic activity of the microbiome, and dietary metabolites may contribute to brain dysfunction and neuroinflammation depending upon individual genetic vulnerability
Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them.
This is currently being
merged. After a discussion, consensus to merge this into Mechanism of autism was found. You can help implement the merge by following the instructions at Help:Merging and the resolution on the discussion. Process started in June 2023. |
The pathophysiology of autism is the study of the physiological processes that cause or are otherwise associated with autism spectrum disorders.
Autism's symptoms result from maturation-related changes in various systems of the brain. [1] How autism occurs is not yet well understood. Its mechanism can be divided into two areas: the pathophysiology of brain structures and processes associated with autism, and the neuropsychological linkages between brain structures and behaviors. [1] The behaviors appear to have multiple pathophysiologies. [2]
There is evidence that gut–brain axis abnormalities may be involved. [3] [4] [5] A 2015 review proposed that immune, gastrointestinal inflammation, malfunction of the autonomic nervous system, gut flora alterations, and food metabolites may cause brain neuroinflammation and dysfunction. [4] A 2016 review concludes that enteric nervous system abnormalities might play a role in neurological disorders such as autism. Neural connections and the immune system are a pathway that may allow diseases originated in the intestine spread to the brain. [5]
Several lines of evidence point to synaptic dysfunction as a cause of autism. [6] Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion. [7] All known teratogens (agents that cause birth defects) related to the risk of autism 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, there is strong evidence that autism arises very early in development. [8]
In general, neuroanatomical studies support the concept that autism may involve a combination of brain enlargement in some areas and reduction in others. [9] These studies suggest that autism may be caused by abnormal neuronal growth and pruning during the early stages of prenatal and postnatal brain development, leaving some areas of the brain with too many neurons and other areas with too few neurons. [10] Some research has reported an overall brain enlargement in autism, while others suggest abnormalities in several areas of the brain, including the frontal lobe, the mirror neuron system, the limbic system, the temporal lobe, and the corpus callosum. [11] [12]
In functional neuroimaging studies, when performing theory of mind and facial emotion response tasks, the median person on the autism spectrum exhibits less activation in the primary and secondary somatosensory cortices of the brain than the median member of a properly sampled control population. This finding coincides with reports demonstrating abnormal patterns of cortical thickness and grey matter volume in those regions of autistic peoples' brains. [13]
The imbalance in excitatory and inhibitory neurotransmission, particularly involving neurotransmitters such as glutamate and gamma-aminobutyric acid, has also been proposed as a potential mechanism underlying the behavioral and cognitive manifestations observed in individuals with ASD. [14]
Brains of autistic individuals have been observed to have abnormal connectivity and the degree of these abnormalities directly correlates with the severity of autism. Following are some observed abnormal connectivity patterns in autistic individuals: [15] [16]
Listed below are some characteristic findings in ASD brains on molecular and cellular levels regardless of the specific genetic variation or mutation contributing to autism in a particular individual:
46% to 84% of autistic individuals have GI-related problems like reflux, diarrhea, constipation, inflammatory bowel disease, and food allergies. [18] It has been observed that the makeup of gut bacteria in autistic people is different than that of neurotypical individuals which has raised the question of influence of gut bacteria on ASD development via inducing an inflammatory state. [19] Listed below are some research findings on the influence of gut bacteria and abnormal immune responses on brain development: [19]
A number of discrete brain regions and networks among regions that are involved in dealing with other people have been discussed together under the rubric of the social brain. As of 2012 [update], there is a consensus that autism spectrum is likely related to problems with interconnectivity among these regions and networks, rather than problems with any specific region or network. [20]
Functions of the temporal lobe are related to many of the deficits observed in individuals with ASDs, such as receptive language, social cognition, joint attention, action observation, and empathy. The temporal lobe also contains the superior temporal sulcus and the fusiform face area, which may mediate facial processing. It has been argued that dysfunction in the superior temporal sulcus underlies the social deficits that characterize autism. Compared to neurotypical individuals, one study found that individuals with high-functioning autism had reduced activity in the fusiform face area when viewing pictures of faces. [21][ verification needed]
ASD could be linked to mitochondrial disease, a basic cellular abnormality with the potential to cause disturbances in a wide range of body systems. [22] A 2012 meta-analysis study, as well as other population studies show that approximately 5% of autistic children meet the criteria for classical mitochondrial dysfunction. [23] It is unclear why this mitochondrial disease occurs, considering that only 23% of children with both ASD and mitochondrial disease present with mitochondrial DNA abnormalities. [23]
Serotonin is a major neurotransmitter in the nervous system and contributes to formation of new neurons ( neurogenesis), formation of new connections between neurons ( synaptogenesis), remodeling of synapses, and survival and migration of neurons, processes that are necessary for a developing brain and some also necessary for learning in the adult brain. 45% of ASD individuals have been found to have increased blood serotonin levels. [16] Abnormalities in the serotonin transporter have also been found in ASD individuals. It has been hypothesized that increased activity of serotonin in the developing brain may facilitate the onset of ASD, with an association found in six out of eight studies between the use of selective serotonin reuptake inhibitors (SSRIs) by the pregnant mother and the development of ASD in the child exposed to SSRI in the antenatal environment. [24]
The study could not definitively conclude SSRIs caused the increased risk for ASD due to the biases found in those studies, and the authors called for more definitive, better conducted studies. [25] Confounding by indication has since then been shown to be likely. [26] However, it is also hypothesized that SSRIs may help reduce symptoms of ASD and even positively affect brain development in some ASD patients. [16]
immune dysregulation, GI inflammation, malfunction of the ANS, genetic and metabolic activity of the microbiome, and dietary metabolites may contribute to brain dysfunction and neuroinflammation depending upon individual genetic vulnerability
Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them.