Etiology of Autism Spectrum Disorder

  Karina Dolgilevica 07.01.2013

  Word count: 1 637

  5) There are many questions about the etiology (cause) of Autism Spectrum Disorder. Please pick one (1) perspective

(neurological, cognitive, or social) and discuss the research that

explores ASD.

  (1500words +/- 10%) The investigation of the causes of Autism Spectrum Disorders (ASDs) has been surrounded by myth and controversy throughout history, mainly because of difficulties of diagnosis and a lack of feasible evidence. With technological progress, however, a large body of scientific evidence has emerged during the past few decades. The fields of neuroscience and neurogenetics have contributed enormously to our understanding of ASDs, but the underlying cause of this complex neurodevelopmental disorder is yet to be discovered.

  Autism Spectrum Disorder comprises a range of conditions that vary in their individual characteristics and severity, but the main symptoms found in people diagnosed with ASD are a lack of empathy, the inability to interpret and understand other peoples’ emotions and feelings, and impaired verbal and non-verbal communication and social interaction, often accompanied by repetitive behaviours (Kanner, 1943; Geschwind, 2007; The National Autistic Society, 2012). This essay is going to look at recent research evidence from studies of the basis of ASD, focusing mainly on the recent genetic and neurobiological research within the field of neurology. Contemporary research indicates a strong association between genes and manifestations of ASD symptoms. ASDs are thought to be of genetic origin and are considered as polygenic, meaning that they are determined by a number of genes, as opposed to a single gene (Chugani, 2000). From very early studies of twins, ASD was believed to be highly heritable (Kanner & Eisenberg, 1955). Later findings have also supported the heritability of ASD (Silverman et al., 2002), and a recent study by Klei et al. (2012) has been investigating common genetic variants and has determined that heritability plays a significant role in ASD. Klei et al. (2012) studied numerous families with more than one member affected by ASD (multiplex) and families with one affected member (simplex). Their findings show that offspring of multiplex have a higher risk of developing ASDs. Current research concludes that more than twenty different genes could be giving rise to ASD, for example those genes responsible for grammar and language (Fisher, 1998). Furthermore, environmental factors, such as the development in the womb, a range of individual differences in the anatomy of the brain and genotype of the individuals diagnosed with ASD, must to be considered and highlighted when studying the origin of ASD. Researchers apply various methods in their studies to prove the genetic basis of these conditions, but the attempt at isolating gene(s) causing specific ASD symptoms and linking then together have so far proved to be very complex and relatively unsuccessful. Statistics show that a vast majority of individuals diagnosed with ASD are male, with a ratio of four males to one female. It has been widely found that an autistic brain contains higher levels of testosterone hormone than a normal human brain, (Baron-Cohen, 2005; Hu, 2011; Green, 1997), which has encouraged researchers to look at the neurodevelopment of an autistic brain in more detail and to try to illuminate the question of the sex bias in autism.

  Some of the latest research investigating sex bias in autism, has found some evidence that explains abnormal levels of testosterone in the autistic brain (Sarachana et al., 2011). A study conducted by Sarachana et al. (2011) has concluded that higher levels of testosterone during the pre-natal development of the foetus are more likely in the male foetus and could be contributing to the development of autism. Earlier research had demonstrated that a gene called retinoic acid-related orphan receptor (RORA), which is responsible for the development of the cerebellum, had been less expressed in autistic individuals. RORA has been found to be responsible for the accumulation of testosterone by regulating the gene in control of the aromatase enzyme that converts testosterone to oestrogen (Baron-Cohen et al. 2011). Normal functioning of aromatase can be restricted if RORA is under-expressed, which subsequently causes the accumulation of testosterone. Moreover, excess testosterone may keep repressing the expression of RORA. The female foetus contains more oestrogen hormone and it is more likely to promote RORA than repress it (Sarachana et al. 2011). These findings explain why the build-up of excess testosterone is less likely in females, which could explain the male-female ratio of 4 to 1 in people diagnosed with ASD and possibly add another likely contributor to the source of development of ASDs. Neuroimaging studies demonstrate the difference between workings of a normal human brain and that of an individual diagnosed with ASD, by examining the neuroanatomy of an atypically developing human brain and nervous system. From the evidence of various magnetic resonance imaging (MRI) studies many developmental disorders, such as autism, indeed show structural and functional differences in the biology and chemistry of the brain (Green, 1997; Komuro & Rakic, 1998). The activation of numerous brain regions (in particular temporal, parietal and occipital regions as well as temporal lobes and amygdala, involved in language and social cognition) appear to differ from case to case due to heterogeneity of ASD. Perhaps one of the biggest differences observed in an autistic brain is the atypical wiring (Baron-Cohen et al. 2011) which appears to be caused by a speeded up growth of the brain at a wrong period of time, around the age of 12 months, but later (around 10 years of age) the brain is of a normal size, but the wiring of the brain becomes abnormal as a result, which causes an autistic brain to function differently from a normal human brain (Minshev et al. 2006; Taylor, 1993). Abnormal wiring of the brain is also believed to be initiated by abnormal neuronal migration during the early development of the foetus where neurons travel from the original place to their ultimate destination in the brain (Komuro & Rakic, 1998) Nadarajah et al. 2001). Disturbances in multimodal stimulation, that affects the neural development of the foetus is also implicated in the abnormal development, and could potentially be causing ASD symptoms in post-natal development (Edelman, 1987; Gottlieb, 1997; Lickliter, 2005). Neuroimaging studies consistently found that cerebral volumes of an autistic brain are increased (“macrocephaly”), particularly in the temporal, parietal and occipital regions, in most cases in white matter, which is an indication of disturbance in the neural network during early development (South et al., 2008;Smith, 2011; Frazier et al., 2012). One of the recent studies conducted by Frazier et al. (2012) includes a longitudinal study that followed and measured changes in the corpus callosum of 23 children diagnosed with autism. The study involved two MRI screenings per participant with a two year gap between screenings. Frazier et al. (2012) found a persistent reduction in overall volume of corpus callosum in all the autistic subjects relative to the control group of subjects. Findings of an MRI study (Chura et al. (2009) looking at the effects of the foetal testosterone on the autistic brain are consistent with findings of Frazier et al. (2012) with regard to the size of the corpus callosum, but also observe asymmetry in the corpus callosum. The conclusions of the Chura et al. (2009) study suggest that such asymmetry of corpus callosum is shaping and

affecting the structural and functional development of the brain, behaviour, and cognition in people with ASD.

  A timesaving method of diagnosis of ASD has been recently devised by the Institute of Psychiatry in London (Laurance, 2010). This involves an MRI scan and special software (involving facial recognition and handwriting techniques) that allows a distinction to be made between the normal brain and an autistic brain. The procedure only takes about fifteen minutes. The software is programmed to respond to certain patterns of autistic brains. This expeditious method is still in development, but could allow the screening to be used for common diagnostic purposes in the future, especially with children, which would probably allow earlier diagnosis of ASDs and encourage people to come forward. The research team has tested 20 adult male subjects with ASD against 20 normal subjects during the programming stage of the software. One of the other advantages of such technology is that it is more equipped to pick up on subtle and intricate neuroanatomical details. Further research would be necessary to ensure that this method is sufficiently accurate and reliable. This non- invasive and efficient diagnostic test would potentially contribute to our knowledge of the autistic brain and perhaps help classify the diagnosed individuals, but it is not very likely to serve as a means to identifying causes of ASD. Being able to match the studied subjects better would decrease the heterogeneity of the ASDs and allow the decrease of some of the inconsistencies gathered from various MRI studies.

  Studying the ASD and its origin proves to be very challenging due to the complexity of the human brain and the complex nature of the disorder itself. Contemporary research is heading towards more efficient and accurate methods of diagnostic measures of ASDs. The search for the cause of ASD needs to be directed towards the opportunity of being able to test and follow subjects of a greater risk of developing ASD from much earlier stages of development, during the period of early neural development. There are many methodological limitations attached to the extensive research which has been conducted so far and therefore drawing definite conclusions is impossible at this stage. Although the scientific community has observed and reviewed many advances in the research of ASDs and established a few potential causes, such as genetic, abnormal early development of the brain and biochemistry, which look credible, perhaps an earlier and more careful diagnosis of cases is required to reduce the heterogeneity of ASD more longitudinal studies, and a more systematic programme that would allow a clearer classification, would potentially reduce the complexity of our definition of the disorder, and help to discover the cause/causes of ASDs, leading to better treatment.

  

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