The Causes of the Autistic Disorder
by Marina Tonti (Nov 10, 2008)
This essay aims to present various causes of Autism, on psychological, behavioral, environmental, neurobiological, and genetic areas of study. A critical analysis follows, and suggestions are made, for areas of further research that needs to follow, in order to approach the Autistic Disorder in a holistic manner, and become more effective in its treatment. ΄
In 1940s both Leo Kanner and Hans Asperger independently discovered this developmental disorder which according to studies that took place in USA, it afflicts one in 150 children. By coincidence, they both named this syndrome «autism», from the Greek word autos, meaning «self», due to the reason that the most conspicuous feature of the disorder is a withdrawal from social interaction. Later on the term ADS «autism spectrum disorder» was used, to denote that although the disorder has some characteristic symptoms, has many related variants that range widely in severity (Vilayanur et al, 2007). The word «autism» was also used by Bleuler to indicate a cardinal sign of schizophrenia as a distinct syndrome, which led to a 30 years of controversy, questioning if autism indeed is different than adult psychoses. Autism was initially recognized as a disorder of brain development, which is a long life handicap, despite important gains. Later studies showed that Autism is different than childhood schizophrenia, language and other developmental disorders, syndromes seen in institutionalized or suffering from maternal deprivation children. Finally, in the early 1970’s, studies showed developmental gains in children, that were educated with active rather than passive techniques, and parents acted as cotherapists (Fombonne, 2003).
Autism is a neurodevelopmental disorder of childhood, presenting deficits, in communication, social interaction and behavior (Gallagher et al, 2003). The diagnosis of Autism, depend on a triad of deficits as impaired social interaction, impaired communication, restricted interests and repetitive behaviors. Autism is a behavioral diagnosis, with no single cause or etiology (Belmonte et al, 2006). Some other diagnostic signs of autism are social isolation, lack of eye contact, poor language capacity, absence of empathy, problems with understanding metaphors, difficulty with miming other people’s actions, display an eccentric preoccupation with trifles, ignore important aspects of their environment, especially their social surroundings and show an extreme aversion to certain sounds (Vilayanur et al, 2007).
Psychological characterization of core deficits in individuals with autism, contribute in the search of factors in the areas of etiology and pathogenesis of various conditions defined by early onset social disabilities. Psychological research focused on disruptions of symbolic and conceptual development, specific social cognitive mechanisms, and general perceptual and cognitive learning mechanisms (Volkmar et al, 2004). One of the most ingenious psychological theory that tries to explain the autistic disorder is the «theory of other minds.» Frith and Baron-Cohen argued that people with autism cannot interact socially because they lack a specialized neural circuitry in the brain that allows them to create sophisticated hypotheses about the inner workings of other people’s minds (Vilayanur et al, 2007).
Over the last decades, research in Autism, and other related conditions, has increased dramatically in both quantity and quality. Recent epidemiological studies have shown that ADS are common, psychological research has helped to develop new developmental models for the disorder, and there have been significant advances in molecular genetics, as well as understanding the underlying neurological processes (Volkmar et al, 2004). Autism is not associated with localized damage, but it is primarily caused by the effects of multiple genetic risk factors on many or all functional brain systems. Thus Autism can be viewed, as a disturbed disorder, on various levels of study, from genes to anatomic brain development, to functional brain organization and to behavioral sequelae (Müller, 2007). With the exception of Rett syndrome, there is no current evidence that other DSM-IV subtypes of autism are linked to any particular genetic or nongenetic disorder (Muhle et al, 2004).
Autism used to be considered largely psychogenic, but research in the last two decades, proved that autism is largely caused by genetic factors that lead to abnormal brain development. It is suggested that Autism is a genetic defect in the control of neurodevelopment which result in structural and functional changes predisposing an individual to autism (Nicolson et al, 2003). Other studies demonstrate that neuroimmune abnormalities occur in the brain of autistic patterns, and this may contribute to a diversity of autistic phenotypes (Pardo et al, 2005). One of the most common genetic causes of Autism Spectrum Disorders (ASD) could be duplications on chromosome 15, which are located in the Angelman-Prader-Willi region (15q11-q13). Duplication may result from partial trisomy 15, or from intrachromosomal duplications (Cohen et al, 2007). Another study shows that specific conditions, such as fragile X anomaly and tuberous sclerosis, account for a small proportions of the cases (Rutter, 2005). Furthermore, on resent studies, molecular approaches showed that dysregulation of intracellular signalling through the TSC1/2-mTOR pathway may also lead to autism, and to socialization deficits (De Vries, 2008).
In about 5% of the cases of Autism, chromosomal and DNA anomalies are reported, with most common being fragile X syndrome followed by maternally inherited trisomy or tetrasomy of chromosome 15q11.2. Further research also has proven an association between Autism, and the deletion of chromosome 2q (Gallagher et al, 2003). Investigations on Fragile X syndrome (FXS) and what role plays within complex genetic and neural network processes may suggest targets for autism research or make suggestions on relation autism to more singular genetic syndromes (Belmonte et al, 2006). An RNA binding and transport protein which regulates the translation of many messages important for synaptic plasticity, is missing or is deficient in FXS or FMRP, in individuals with autistic disorders (Hagerman, 2008).
Another case studied, suggested that mutations in ribosomal protein gene RLP10 located in Xq28, is a modulating mechanism for autism (Klauk et al, 2006). Mutations in Neuroligin Genes (NLGN3 and NLGN4) may also be the cause of autism, although they are not commonly reported, in the autism population (Talebizadeh et al, 2004). Another case of study, reports an association of Per1 and Npas2 with Autism, supporting that the clock genes are implicated in the Autistic Disorder (Nicholas et al, 2007). New clues on Autism mysteries suggest that some rare forms of Autism are linked to vaccination, and mutations on X chromosome (Harvard Medical School, 2003). Later research has showed that mirror neurons, located in the cingulate and insular cortices, may play a role, in empathetic emotional responses. Mirror neurons give the ability to see ourselves as others see us, which is an essential aid for self-awareness and introspection (Vilayanur et al, 2007).
Most cases of autistic disorders are proven to be multifactorial involving, possibly more than 10 susceptibility genes, that interact to produce the phenotype. Even if the genetic causes of autism are well understood, it will be necessary to identify also environmental factors that may contribute to the expression of the symptoms. Genetic and environmental factors are not viewed as mutually exclusive in the investigation of causes of birth defects. Questions have been risen as to if there is a contribution to the risk of autism, due to pre– or neonatal exposure to infectious diseases, due to general factors in pre- and perinatal life, due to the family history, due to exposures to teratogenic drugs or other chemicals. There is also research conducted into gene-environment interactions, as to how we can investigate environmental factors in genetic disorders, such as teratogens, and how do brain-damaging genetic disorders act to increase the risk of autism (Rodier et al, 1998).
Further epidemiologic studies indicate prenatal infections such as rubella and cytomegalovirus account for a few cases of autism (Muhle et al, 2004). In accordance with recent UK AND Swedish studies, nearly 60% of pervasive development disorders were atypical autism. Epidemiological studies contacted showed that there is no ethnic difference in the high prevalence of pervasive developmental disorders. (Kurita, 2006).
There is no single genetic or cognitive cause for the diverse symptoms defining Autism. If different features of autism are associated with different genes, brain regions, core cognitive impairments, it seems likely they will respond to different types of treatment. (Happé et al, 2006)
Further research needs to be done in order to understand underlying brain abnormalities, causes of autism, and enhance early detection, prevention, diagnosis, and treatment. The combination of continually evolving methodologically and technologically, will only yield to many more exciting and important clues to autism’s etiology and pathogenesis, and bring us closer to the goal of earlier and successful intervention, in order to minimize the symptoms.
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