Autism Spectrum Disorder & SHANK3 Gene
The way our brains develop give rise to how we understand the world. But what happens when an ingredient to making a brain is missing?
What is Autism Spectrum Disorder?
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that encompasses a wide range of different diagnoses. Within the spectrum, there are various manifestations of the condition with autism and Asperger’s syndrome the most commonly referred to. ASD differs from other neurodevelopmental conditions as it is characterized by impaired social behaviour, as well as reduced muscle tone and varying degrees of intellectual disability. The root of ASD has a strong genetic basis that has been extensively studied. What has only recently been discovered is how these genetic distinctions contribute to behaviour that is presented in these conditions.
Genetic Basis of ASD
“Science is the process that takes us from confusion to understanding” – Brian Green
To understand what current research knows, it is important to cover some foundational concepts. Humans inherit genes from their parents through 23 pairs of chromosomes. The genes we inherit encode for proteins which ultimately give rise to every aspect of our being. SHANK3 is one such gene that is found on chromosome-22. This gene contains the recipe needed to make the SHANK3 protein which is integral in neuron-to-neuron communication. Mutations, or complete absence, of the SHANK3 gene is associated with PhelanMcDermid syndrome; a cognitive disability where regions of the brain associated with behaviour and social communication are affected.
This is where our story begins.
SHANK3 & ASD
In 2014, French researchers identified that SHANK3 mutations also occur in ASD individuals who are not diagnosed with PhelanMcDermid syndrome. This is a significant finding as it relates a gene deficiency to the behavioural characteristics presented in ASD. Prior to this, scientists had general assumptions of the way missing genes could play a down-stream effect in influencing behaviour. With this knowledge, came the power to predict it.
A Deeper Look
“Look deep into nature, and you will understand everything better.” – Albert Einstein
In 2019, researchers at the Functional Neuroimaging Lab (Italy) published a paper in The Journal of Neuroscience aiming to further collective understanding of SHANK3 and its role in ASD. The purpose of their experiment was to observe how insufficient neuron-toneuron connections contribute to disfunction in behaviours such as social communication. As social creatures, we depend on our ability to understand and perform in social contexts. When this ability is impaired, stereotyped ASD behaviours transpire. The brain region responsible for governing this social awareness is called the ‘pre-frontal cortex’. This region, located behind the forehead, was the main area of focus in this study. The research concentrated on male mice who were missing both pairs of the SHANK3 gene. When contrasted to groups who were not genetically deficient, a couple of things were discovered. Firstly, the extent of connectivity between the pre-frontal cortex and other structures was decreased when SHANK3 was missing. Further, mice that were gene deficient had reduced grey-matter volume.
What Does This Mean?
To a certain extent, everything in the brain is connected.
If the pre-frontal connections are disrupted, then communication with other brain regions is impacted. The study’s findings suggest that SHANK3 deficiency not only predisposes to sociocommunicative impairments but may also be responsible for other intellectual disabilities as the pre-frontal cortex cannot communicate with other areas of the brain. Grey matter consists of the bulk of neurons. If grey matter is reduced, then that’s an indication of a reduction in the number of neurons. The study’s findings imply that not only is communication between structures impacted by SHANK3 deficiency but the number of neurons able to facilitate communication is also affected.
Future Exploration
This study provides mechanistic explanations for particular ASD behaviours. However, there still remains unanswered questions. For example, how can the broad range of ASD conditions be attributed to just one genetic deficiency? Likewise, what contributes to this deficiency in the first place? In terms of the experiment itself, it focused on male mice but whether these findings translate into humans, or even female mice, requires further investigation.
Good vs Evil
“Science in itself is morally neutral; it becomes good or evil according as it is applied.” – Aldous Huxley
Finally, whenever a study highlights biological differences between people, we have to ask – how can false assumptions related to these findings be interpreted?
This isn’t a trivial question. Inaccurate interpretations of biological research have a history of fuelling dangerous ideologies such as eugenics. This does not imply that scientific research into these differences should be restricted, rather, as global citizens we should consider how to make informed decisions with this scientific information. Moving forward, there are several concepts of this research area that contribute to broader 21st century topics. With growing interest in bioengineering and “designer babies”, the question is reiterated – will genetic conditions such as autism spectrum disorder one day be a thing of the past?
Only time will tell.
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