The Significance of Research in the Autism Spectrum

How well has autism been researched and documented? Well, that has been a question asked for many decades. Research is vital to improving current practices and models for interacting with individuals with autism. Additionally, such research can both improve and find new neurodevelopmental disorders. Fortunately, the knowledge and specific biological causes of autism that have been discovered are only increasing. 

Autism, otherwise known as the autism spectrum disorder (ASD), refers to "a developmental disability that can cause significant social, communication and behavioral challenges," as defined by the Centers for Disease Control and Prevention. So far, researchers believe that the cause of autism is a combination of multiple factors: genetic factors, environmental influences, and heredity. 

Multiple studies have found that dopamine concentrations, a neurotransmitter in the brain known to have a regulating effect on feelings of pleasure and motivation, are altered in individuals with ASD (Zeliadt 14). Neurotransmitters are chemical messengers that are released in the synapse, which is the space between two neurons. 

A spontaneous mutation in the dopamine transporter gene SLC6A3 has been linked to the onset of autism (Ross 13). SLC6A3 is a gene that codes for a dopamine regulation protein, further validating the hypothesis that dopamine regulation has a solid correlation to autism. Researchers were able to support this link by testing the gene mutation on fruit flies. This mutation, later named T356M, created a single point-mutation (alteration in one amino acid), which affects the resulting protein. This altered protein, instead of increasing the dopamine concentration in the brain, actually decreases it. When this mutation was induced in the fruit flies, the researchers observed hyperactivity, a common characteristic of autism.

Like the T356M mutation, there are many other variants in the dopamine transporter gene. However, that all impair the function of the dopamine regulator protein and thus decrease dopamine concentrations in the brain. For example, instead of altering the amino acid sequence in the protein, one mutation alters the concentration of the transporter protein itself, thus decreasing dopamine transport. 

Another researcher, Mustafa Sahin, MD, Ph.D., found another relationship between autism and dopaminergic neurons (McCarthy 21). This special type of neuron is found in the midbrain and is responsible for dopamine synthesis or creation. His study primarily relied on a finding from 2008, which concluded that the 16p11.2 chromosomal region is linked with autism spectrum disorder (ASD).

Sahin's team formulated a method of separating induced pluripotent stem cells— made from patients' stem cells and containing 16p11.2 copy number alterations (a difference in the number of copies of a specific gene from individual to individual) — into dopaminergic neurons. The team then, at that point, studied how neurons missing the 16p11.2 chromosomal region acted in a dish. Such an experimental model was extremely complex as these neurons contain more than 1,000 sensors which were used to determine neuron activity in the experiment. 

"We discovered that dopaminergic neurons that are missing this 16p11.2 region were hyperactive compared to the control cells," says Sahin. This hyperactivity was later linked to the neuron misfiring or causing excess sensors to go off when it is not necessary, thus increasing the neuron activity. 

The group also utilized their dopaminergic neurons to check whether they could discover pathways and drugs that decrease dopaminergic neuron misfiring. Utilizing data from prior investigations, the group zeroed in on the KCTD13 gene in the 16p11.2 chromosomal region, a gene known to control the RhoA pathway. The RhoA pathway is known to control nerve cell development. 

Adding rhosin, a medication that explicitly represses RhoA's pathway activity eased back misfiring of the dopaminergic neurons with 16p11.2 deletions to a level equivalent to that of control cells. 

"Rhosin basically protected the strange organization action of the 16p11.2-erasure neurons," says Sundberg, first author of the published study.

Such findings from this study provide a new model for pharmaceutical companies to address autism, as well as bring their product to market through FDA approval and multi-phase trials. More studies and research in the RhoA pathway, as well as other pathways, may increase the chances of a therapeutic being available to the general public.

The limiting factor for many of these experiments and findings is the availability of mapped genes for individuals on the autism spectrum. Thus, there has recently been a movement to improve and increase the number of mapped genes recorded.

Nickolas Johnston, a 15-year-old, was one of 100 young people picked to have their whole gene codes recorded with a goal to foster more targeted medicines for autism. 

Johnston and his family reported that the spectrum nature of autism makes it unique for each individual — thus, it is difficult to create a therapy that applies to all those on the autism spectrum.
Research about autism and other neurodiverse conditions is especially important because it raises awareness of the neurodiverse community, which pushes forward tips for parents to support their child with autism.

The goal of most research, especially within the autism aspect, aims to help individuals with autism as well as their parents provide assistance in an assortment of settings, from the home, classroom, and community.

Current research has provided many goals for parenting which includes a consistent schedule, rewarding satisfactory or good behavior, making sure that the home area is safe for kids, and paying attention to the child’s sensory inputs as well as sensitivities.  

In all, further advancements in autism research will provide the basis for the future of understanding autism and neurodivergence, an essential tool priceless for many.