Autism spectrum disorders (ASDs) are ten times more prevalent now than earlier in the 1980’s and 1990’s. Currently, about 0.6% of the population is said to have an ASD (Happe, 2006). Autism spectrum disorder (ASD) is a term coined by doctors to make it understood that there are many related variants that range widely in severity yet share characteristic symptoms. Some diagnostic symptoms are social isolation, poor or no eye contact, inadequate language capacity and absence of empathy. People with ASD often display eccentric preoccupation with objects while ignoring important aspects of their surroundings, especially the social aspect (Ramachandran and Oberman, 2006). The neurological basis has been elusive and most attention in the 1990’s focused on the amygdala, hippocampus and cerebellum (Bailey, Braeutigam, Jousmaki, and Swithenby, 2005).
According to the criteria for autism from the DSM-IV-TR, repetitive and stereotyped patterns of behavior may be present at cognitive (obsessive routines) and motor (hand flapping and rocking of body) levels. Sensory and motor disadvantages have been linked to early detectable symptoms occurring within the first few months of life before the onset of social dysfunctions (Mizuno, Villalobos, Davies, Dahl, and Muller, 2006). Neurodevelopmental disorders such as ASD involve poor social interaction and unbalanced mentalizing abilities, connected to abnormal regional cerebral activity. The most observed discrepancies with people with ASD are increased volume of the whole brain, parietal-lobe, and cerebellar hemisphere, as well as unusual sizes of the amygdala, hippocampus, and corpus callosum (Mazur-Kolecka, Cohen, Jenkins, Kaczmarski, Flory, and Frackowiak, 2007). The core abnormalities in the pathology of autism in the brain are located in the amygdala, adjacent limbic structures, and the corpus callosum (Anckarsater, 2006).
The Amygdala is a small structure about the size of a pea in the group of structures known as the limbic system located in the temporal lobe of the brain. People with a compromised amygdala have an inability to discriminate facial expressions and show poor social judgement (Pickett, 2001). Damage to the amygdala is associated with impaired social cognition and understanding emotions (Anckarsater, 2006). The complex limbic system circuitry and the close relation to the amygdala strengthen its association to autism. The heavily reciprocal pathways provide the amygdala with visual cues of faces and facial expression, body posture and gestures, and cues of specific sounds. The amygdala is responsible for decoding these cues and assigning an emotional value to the cues it receives and transmitting it to higher order areas of the brain. In monkeys and rats studied with damage to the amygdala there may be contributions to increased anxiety (Kuemerie, Gulden, Cherosky, Williams, and Herrup, 2007).
The thalamus is known as a sensory gate receiving afferent messages from sensory receptors and projecting received sensory messages to cortical regions. The thalamus is part of the cerebello-thalamo-cortical pathway. Early decreases in Purkinje cells in autism can cause weaknesses in this pathway which are inherent in many people with ASD (Mizuno, Villobos, Davies, Dahl, and Muller, 2006). Pickett (2001) suggests that the synapses between neurons of the brain are abnormal in more than one site, to include the limbic system and brainstem. It is in the cell to cell connections or synapses that there are structural abnormalities.
Neuronal progenitor cells (NPCs) in blood sera of children with autism leads to altered early neuronal development that leads to autism. The proliferation of the neuronal network of processes and synaptogenesis are altered in autism due to the reduced NPCs but stimulates cell migration, development of small neurons with processes, and the length of processes. Blood of some people with autism contains altered levels of serotonin, a monoamine neurotransmitter that regulates neurogenesis neuronal differentiation, neuropil formation, axon myelination, and synaptogenesis (Mazur-Kolecka, Cohen, Jenkins, Kaczmarski, Flory, and Frackowiak, 2007). The neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) is associated with autism in that there are elevated 5-HT levels in the blood of people with autism. Serotonin re-uptake inhibitors (SSRIs such as sertraline and fluoxetine) are beneficial in treating autism. In humans, there is a complex protein called the serotonin transporter on presynaptic cell membranes that regulate the amount of serotonin that there is. There are fifteen known serotonin receptor subtypes, postsynaptically (Pickett, 2001). It has been established that the presence of more than 99% of serotonin in the platelets leads to the theory that platelet serotonin accounts for the hyperserotoninemia in people with autism. Hyperserotoninemia in platelets relates to 5-HTT in that it regulates the serotonin neurotransmitter. 5-HTT is the candidate gene in autism in which selective serotonin reuptake inhibitors combat ritualistic behavior in autism. The specific location of gene SLC6A4 in the susceptible region on chromosome 17q is targeted (Guhathakurta, et al. 2006).
The cerebellum in the brain is a structure responsible for coordinating complex voluntary muscle movements (Ramachandran & Oberman, 2006). The cerebellum plays an important role in sensory tracking, prediction, association, and anticipatory learning. In autism, cerebellar activation is found to be abnormally low during selective attention and abnormally high during a simple motor task. The reduction in purkinje cells in specific regions of the sutistic cerebellum could release some neurons in the deep cerebellar nuclei from inhibition. This can result in an abnormally strong physical connectivity along the cerebello-thalamocortical circuit making abnormalities in cortical maps of motor function and face processing, as well as abnormally large frontal lobes (Kuemerie, Gulden, Cherosky, Williams, and Herrup, 2007). Abnormalities include increased thickness, high neuronal density, neurons in the molecular layer, neuronal disorganization, poor definition of grey and white boundaries, neuronal heterotopias and focally increased numbers of single neurons in the white matter (Kleinhans, Schweinsburg, Cohen, Muller, and Courchesne, 2007).
Cerebellar damage inflicted by a stroke in a child sometimes exhibit tremors, swaying gait, and abnormal eye movements rarely seen in autism. The changes seen in the area of the brain may be unrelated side effects of abnormal genes whose other effects are the true causes of the disorder. The Mu wave is emitted anytime there is a voluntary muscle movement. In autism, the Mu wave is blocked anytime a person makes voluntary movement such as opening or closing one’s hand and blocked even when someone else performs the same action (Ramachandrun & Oberman, 2006). The cerebellum needs both neuronal and non-neuronal cells to interact cohesively to have a normal functioning organ. The altered biochemical maturity of cells adhesive molecules could explain the observed alterations in structure and function of the cerebellum (Pickett, 2001).
Most of the brain’s cognitive and executive functions are manifested by large numbers of neurons that are distributed within and around different specialized brain areas (Uhlhaas & Wolf, 2007). Increase in brain volume in people with autism may be caused by an increase in non-neuronal elements such as astrocytes and intercellular tissue, which are by and large rarely seen in the corpus callosum. Three to four year old children with ASD have increased cerebral volume but also exhibit smaller corpus callosums when adjested for cerebral volume. Structural abnormalities tend to be more elevated in children with more classical autism as compared to those with fewer autism symptoms (Begor-Megiddo, et al. 2006). Indications of an abundant lose of white matter growth across cerebral lobes and an increase in white matter volume in myelinating frontal white matter, along with the decreased size of the corpus callosum indicate atypical neuronal connections in the autistic brain (Mizuno, Villabobos, Davies, Dahl, and Muller, 2006).
In conclusion, the structures of the brain may be altered but the connections need to be the same for a child to grow without autism. If the synapses do not link because of blockage in the disappearances of white matter, lack of connectivity between cells, or serotonin saturation then there is a high possibility that the child will have autism. Mutations in the brain formation are not conclusive to causing autism. What is conclusive is that there are many traits which all children and adults with autism share. It is a highly heritable disorder characterized by symptoms such as social inadequacies, eccentric behavior, isolation, abnormal or lack of eye contact, and a lack of emotional understanding.
There seems to be a common gene SLC6A4 chromosome 17q which is associated with autism. Further studies need to be carried out with gene therapy. The serotonin reuptake inhibitors help people with autism. The more research on neuronal pathways and neurons then the more help that can be offered to treat this disorder. In the meantime, parents and teachers should take advice from their doctors on treating the symptoms and being open to as much new scientific information as possible. Knowing the symptoms and matching the symptoms up with therapies that have helped others is the right path to take. The brain can be an elusive and mysterious organ but at the same time the most fascinating. Solutions to this disorder are awaiting.
UNLV Library References
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