The current research in autism and epigenetics looks at environmental factors that influence gene expression, opening doors for new levels of diagnosis and possible therapies.

What Is Epigenetics?

Epigenetics is the study of how environment and behavior can cause changes that affect the way a person’s genes work. This is different from genetic changes that can alter a DNA sequence. Epigenetic changes are reversible, but they can influence how the human body computes a DNA sequence. 

A critical factor in epigenetics is gene expression, which is how often, or when, the genes create proteins. Genetic changes — the ones that can alter a DNA sequence — can change which protein is made. Epigenetic changes, however, can turn specific genes on or off.

Diet and exercise, for instance, are good examples of an epigenetic change because of the connection between genes and the environment. 

Autism & Epigenetics

The research into what causes autism spectrum disorder (ASD) incorporates epigenetics. In addition to a genetic component of the development of the condition, researchers for JAMA Psychiatry have also been looking at the likelihood of environmental factors that may increase the chances of a child developing ASD.

Current research suggests that a few inherited genes are enough to lead to the development of autism. However, these “autism genes” only represent the risk that an infant will develop autism. They are, by no means, the only genetic factors present in that combination. 

The growing body of evidence suggests that the threshold will be met as the result of not only genetic susceptibility but also the environmental factors that play a role in genetics. 

Environmental Epigenetics

It is at this point that epigenetics, as the study of the factors that influence gene expression, intersects with autism research. Specifically, it is environmental epigenetics, the study of how external (outside) influences modify the chemicals that surround a gene’s DNA sequence (also known as gene markers) and how they affect genetic activity. 

In these terms, “environment” can undoubtedly mean pollutants and other forms of chemical exposure, which are widely implicated as risk factors in the development of autism. But “environment” here can also refer to any influence beyond standard genetic mutation. 

One example of such an influence is the parents’ age at the time of conception. As explained in Autism Research, the investigation of the role the father’s age at conception plays in the development of autism falls under the environmental epigenetics umbrella. Similarly, birth complications, such as oxygen deprivation and significant prematurity, are also issues of environmental epigenetics.

Epigenetic Regulation & Gene Expression

Environment constantly influences epigenetics. Everything shapes gene expression —  from diet to exercise, from stress to the rate of alcohol consumption (or lack thereof), and the exposure to pollutants in the air. Any disruption to epigenetic regulation can lead to abnormal gene expression, including mutations and deletions in the gene, which can lead to developmental disorders and problems with neural development. 

Epigenetics allows researchers to examine the relationship between genes and the surrounding environment. As this relationship is better understood, scientists hope to develop therapies and interventions to target the most severe and disruptive autism symptoms preemptively. 

Mapping out epigenetic markers in the brain is critical to understanding gene processing changes in autism.

The mechanisms of epigenetics are the connection points between how genetic and environmental factors regulate the development of the brain and resultant autism risk. Studies of brain tissue have shown that the epigenetic markers mentioned above are different in people with autism and in people in control groups who do not have ASD. 

Epigenetic Modifications

Factors such as air quality, hormones, the patterns of communication between neurons, and diet are all forms of epigenetic modifications. One example is folate.

This B vitamin, which is normally absorbed from food such as legumes, asparagus, and eggs, is required for the synthesis of DNA. A 2020 article in Molecular Autism reported that women who consume food with high folate content even before they conceive had some “protection” from autism. 

Researchers hope that identifying epigenetic differences between standard and affected cells at progressive stages of brain development could unveil more of the causes of autism. 

While the study of epigenetics and autism tends to focus on child development, a 2019 article in the Scientific Reports journal showed that epigenetic changes can also take place in adult brain cells. When this happens, the changes can be “activity-dependent,” activated by brain activity in response to experience or exposure.

These neural responses to changes in the surrounding environment are a key part of adaptive brain functioning. Any disruptions to these responses could be a factor in the form of maladaptive behavior, such as the sensory sensitivity seen in autism. 

A 2017 study in JAMA suggested that in identical twins, if one twin has autism, the other twin will also develop the disorder anywhere from 40% to 90% percent of the time.

Learning more about how the prenatal surrounding environment plays a role in epigenetics could help expectant parents and specialists determine the early risk factors in the parents’ environment that might be implicated in the development of autism. These factors can include everything from where they live to what they eat. This information could shed light on why only one twin develops autism and the other is unaffected.

Current Research in Autism & Epigenetics

The research into autism and epigenetics is a rapidly growing field. Even in 2022, diagnosis and treatment are complex issues because of how varied and diverse the traits and symptoms of autism can be in different people. 

Due to advancements in sequencing technology, researchers have more chances to examine the epigenome at higher resolutions, getting literal insights into the human brain that did not exist even five years ago. 

This has led to an entire body of research and study looking at the epigenetic systems behind the formation of autism, which scientists hope will lead to better forms of treatment and therapy. 

A 2018 study in the Nature Neuroscience journal found that mouse models of autism responded positively to the inhibition of an enzyme that removes a molecule from protein groups in a DNA sequence. The mice in the study did not have the SHANK3 gene, which is a high-risk target that has been implicated in autism. Mutations in this gene result in problems in emotional and cognitive responses in humans as well as mice. 

The researchers in this study discovered that the anti-cancer drug romidepsin, administered in low doses, fully restored gene functioning and “completely reversed the social deficits of the mice” after three days. The effect lasted three weeks in the mice, which is the equivalent of many years for humans.

Biomarkers in Sperm

In January 2021, a study conducted by scientists at Washington State University and Valencia University in Spain found a link between biomarkers in sperm and whether a man is likely to father a child with autism.

Researchers publishing their work in the Clinical Epigenetics journal explained that they discovered DNA methylation regions (a set of genomic features) in sperm from men who had autistic children. They then performed a series of blind tests to see whether they could anticipate which men fathered children on the autism spectrum, which they did 9 times out of 10. 

One of the authors of the study told BioNews UK that this can “potentially assess whether a man is going to pass autism on to his children.” It also opens the door to identifying more of the factors that play a role in autism’s development. 

The researchers noted that while their study is small, it still proved that epigenetic biomarkers can be helpful in diagnosing the likelihood a man may conceive a child who has autism.
Geneticists have discovered that the rate of autism transmission is higher in fathers than in mothers. Further research in the biomarkers found in human sperm could determine how the initial epigenetic changes took place. They could then work backwards to see what, in the father’s surrounding environment, may have precipitated any changes. 

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