General Neuroscience

An Overview of Autism Spectrum Disorders (ASD)

Shreya Gurusankar


Introduction

Autism is a “developmental disability that typically appears during early childhood and can impact a person's social skills, communication, relationships, and self-regulation” [1]. Autism spectrum disorders, known as ASD, are the range of neurological disorders that cause changes in an individual’s social, cognitive, and emotional performance [2]. Since the symptoms of Autism can greatly vary in severity from person to person, it is known as a "spectrum" of disorders. Some individuals with autism need more assistance in their lives than others, and some are “gifted” in areas where their peers are “severely challenged” [2]. From the analysis of recent trends (using data from the Center for Disease Control’s Autism and Developmental Disorders Monitoring network), it is discernible that rates of autism in children have increased significantly, roughly 178% by calculation, in sixteen years [3]. The following review aims to provide a broad overview of ASD from a cognitive, genetic, and neuroanatomical standpoint.
 

The Cognitive Effects of Autism

ASD primarily impacts an individual’s ability to display and practice empathy - a broad term that describes both “the ability to attribute mental states to oneself and others, as a natural way to make sense of agents, and having an emotional reaction that is appropriate to the other person’s mental state” [4]. The lack of empathy is the reason for difficulties that individuals with ASD face in “social and communicative development and in the imagination of others’ minds” [4]. While a model known as the Triad of Deficits (Figure 1)

illustrates the three main channels through which individuals with ASD struggle to make connections with the world around them, the model known as the Triad of strengths (Figure 2)  illustrates the abilities which they possess that are sound or exceptional for their age [4]. Individuals with autism often demonstrate constantly repeated behaviors as a result of their compulsion for, or “obsession” with consistent and regular systems [4]. These include mechanical systems such as light switches, or any system that can be understood methodically [4]. ‘Islets of ability’ indicate that autistic individuals often demonstrate exceptional ability in certain areas (such as Mathematics or Music) which can also be thought of as examples of systems that can be comprehensively broken down and understood [5]. 

 

The Genetics of ASD

It remains unknown whether ASD is a hereditary condition or not. In fact, it is estimated that “Non-genetic factors may contribute up to about 40 percent of ASD risk,” making it a polygenetic disease: a disease that is caused by a variety of factors [6] [7]. However, ASD has a heritability index of 0.9, meaning that the majority of variation amidst the disease’s spectrum itself comes from genetic factors [7][8]. While scientists have yet to identify the exact genes that directly correlate with ASD, it is thought that “many of the genes associated with ASD are involved in the development of thebrain.” The corresponding proteins for these genes  “affect multiple aspects of brain development, including production, growth, and organization of nerve cells (neurons),” all of which are regulatory factors in the functioning and expression of the brain. Due to their major roles in brain development, these genes can be influential in contributing to the presence of ASD [6].  

Certain studies have been conducted to test the extent to which genetics influence ASD, and have suggested that there may be an important correlation between genes and onset of ASD. For example, in a study that analyzed same sex autistic twins, it was concluded that “60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic, (DZ) pairs” [4]. In other words,  the majority of monozygotic twins - identical twins that share the same DNA - both had autism, whereas there were no fraternal twins - twins that have different DNA - that both had autism. This is indicative of a correlation between genetics and the presence of ASD, which was further confirmed by a supplemental study that analyzed the presence of a broader range of social and communicative disorders within twins [4]. This study once again indicated a larger presence in monozygotic twins, with a 92% prevalence of the disease in both individuals, against a 10% prevalence in fraternal, or dizygotic twins [4]. 

 

MEMO1

An example of a gene which may be involved in ASD is MEMO1, a gene responsible for organising “brain cells called radial progenitors necessary for the orderly formation of the brain” [9]. A UNC research team found that in individuals with ASD, the MEMO1 gene is mutated, which indicates that ASD could be caused when the cerebral cortex of the brain is developing in its initial stages [9].  The cerebral cortex is the site of “perception, speech, long-term memory, and consciousness” in the brain. Broadly speaking, the cerebral cortex develops by sprouting “stalk-like structures” from radial glial cells (RGCs) that form at the bottom of the cortex [9]. These RCG cells also produce neurons, which then climb the stalk-like structures to assume their places in the brain as it develops, consequently forming an organised network of neurons which together make up the cerebral cortex [9]. This research shows that the MEMO1 genes have a crucial role in encoding a protein whose primary function is to “organize the tiled radial glial cell scaffold” and therefore facilitate orderly functioning and development of the cerebral cortex [9]. To further investigate the function of this gene, the research team looked at mice which did not possess the MEMO1 gene at all.  In these mice, they  found that there were “neuronal misplacements and disorganized layers” in their cortex as a result of the RCG cells forming an excess of stalks. This excessive growth of stalks was because these mice could not utilize the regulatory mechanisms of the MEMO1 gene [9].  Interestingly, in the mice without the MEMO1 gene, it was also observed that they did not possess any “explorative activity,” thus demonstrating characteristics akin to those often observed in individuals with autism and hence, indicating a correlation between the (absence of the) MEMO1 gene and ASD [9]. 

 

Serotonin

There is also thought to be an association between serotonin and the presence of ASD [4]. Serotonin is a neurotransmitter — a chemical “messenger” that carries signals between neurons — that plays a role in emotions and self-regulation, commonly associated with one’s state of happiness and being [10][17]. Potential alterations in the serotonin transportation pathway and function could therefore be associated with ASD due to its impact on emotion regulation, expression and empathy, which are characteristic traits of individuals with ASD [4]. 

 

The Neuroanatomy of ASD

A study which analyzed the growth and development of the cerebellum and the brainstem in individuals with autism concluded that ASD’s impact on the brain is due to an initially incomplete development (also referred to as hypoplasia) of the brain  as opposed to  “a progressive degenerative process” [11]. The brainstem (the central area of the brain which helps to control crucial functions such as breathing, heart rate, and blood pressure) is an important anatomical factor in ASD because of the correlation between many of ASD’s symptoms and the functions of the brainstem  [12][13].  In general, research indicates that irregularities in the brainstem’s development could have lasting impacts on the formation of the cerebellum and cortex, eventually yielding ASD symptoms [13]. The reason for this is that the brainstem holds a rudimentary  role in brain development, being the “initiating link” for all subsequent brain development to occur [13]. Thus, the brainstem is significant in influencing the entire range of brain functionality and can therefore be critical in influencing the onset of ASD  [13]. 

Similarly, it has been found that individuals with autism possess irregularly dense neuron composition in areas including the hippocampus and the amygdala [4]. Typically, the amount of mature neurons in the human brain is said to increase with age [14]. However, in individuals with ASD, the number of mature neurons are in an excess in childhood and follow  a declining trend into adulthood, in an almost ‘reversed’ manner [14].  This is suggestive of ASD’s degenerative properties in cognition and development, specifically in the emotional sense, as regulated by the amygdala [14]. Moreover, it has been found that the average head circumference of individuals with autism was “disproportionate to height and weight”, with 15-20% of individuals with ASD having a head circumference greater than the 99th percentile relative to their anthropometry; the individual’s exact bodily measurements such as height and weight [7].

 

ASD and Epilepsy

Interestingly, it has also been found that Epilepsy, a similar disorder causing irregularities in behavior due to “clusters of nerve cells or neurons”, is around 20% more common in individuals with ASD, even though  there are currently no known means through which ASD can cause this disorder [15][16]. Although there is no direct link, it is speculated that their “co-occurrence is almost certainly the result of underlying factors predisposing the individuals to both conditions” [16]. These common causative factors, both genetic and environmental, can be traced back to both ASD and Epilepsy given their similar impacts on cognition and behavioral irregularity [16].

 

Conclusion

Developmental disorders such as ASD continue to be a major area of focus for researchers in furthering one’s understanding of the disease and its impacts on individuals. As said by Eva S. Anton, PhD, “For disorders of brain development such as ASD, it is important to understand the origins of the problem even if we are still far away from being able to correct developmental disruptions" [9]. It is hoped that in the future, increased research and understanding of ASD can better help prevent and possibly cure the disease. 


References


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  2. “What is Autism Spectrum Disorder?” CDC. https://www.cdc.gov/ncbddd/autism/facts.html. Retrieved: 06/30/2020.

  3. “Data & Statistics on Autism Spectrum Disorder”. CDC. https://www.cdc.gov/ncbddd/autism/data.html. Retrieved: 06/30/2020.

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  8. “What is heritability?” Genetics Home Reference. June 2018. https://ghr.nlm.nih.gov/primer/inheritance/heritability. Retrieved: 07/02/2020.

  9. University of North Carolina Health Care. 02/07/2019. “The neuroscience of autism: New clues for how condition begins” ScienceDaily.  https://www.sciencedaily.com/releases/2019/07/190702112842.htm. Retrieved: 06/29/2020.

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  11. Hashimoto, T. Tayama, M. Murakawa, K. Yoshimoto, T. Miyazaki, M. Harada, M. Kuroda, Y. February 1995. “Development of the brainstem and cerebellum in autistic patients” PubMed. https://pubmed.ncbi.nlm.nih.gov/7608030/. Retrieved: 07/11/2020.

  12. Crumbie, Lorenzo. Mytilinaios, Dimitrios. Last reviewed: 08/07/2020. “Brainstem” Kenhub. https://www.kenhub.com/en/library/anatomy/the-brainstem. Retrieved: 07/11/2020.

  13. I. Dadalko, Olga, G. Travers, Brittany. 04/10/2018. “Evidence for Brainstem Contributions to Autism Spectrum Disorders” PubMed.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180283/. Retrieved: 07/28/2020.

  14. A. Avino, Thomas. Barger, Nicole. V. Vargas, Martha. L. Carson, Erin. G. Amaral, David. D. Bauman, Meilssa. M. Schumann, Cynthia. 03/04/2018. “Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism” PNAS. https://www.pnas.org/content/115/14/3710. Retrieved: 07/13/2020.

  15. P. Cunha, John. “Epilepsy (Seizure Disorder)” MedicineNet. https://www.medicinenet.com/seizure/article.htm#epilepsy_facts. Retrieved: 07/19/2020.

  16. MC Besag, Frank. 18/12/2017 “Epilepsy in patients with autism: links, risks, and treatment challenges.” PubMed.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739118/#:~:text=epilepsy%20and%20autism.-,Conclusion,based%20on%20recent%20epidemiologic%20studies. Retrieved: 07/28/2020.

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Shreya Gurusankar

Shreya Gurusankar


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