Because ASD occurs more frequently in specific families, ASD appears to be strongly influenced by genetics. However, many of these same families also have an increased risk of other health conditions, such as asthma, epilepsy, heart attacks, obesity, anxiety, autoimmunity, depression, and cancer. A reason for this risk is these families have epigenetically enhanced inflammatory responses. Importantly, these epigenetic changes can happen because of inflammation itself.

Epigenetic changes affect how the cells read the DNA for instructions. Epigenetics are not actual DNA mutations. Therefore, a DNA test not designed to look for epigenetic changes cannot detect those changes.

Epigenetic changes behave like a website blocker. The website exists, but the website blocker does not allow access. Similarly, the DNA exists, but the epigenetic changes block the ability of the cell to read parts of the DNA for instructions.

Importantly, epigenetic changes can also provide access to DNA previously blocked, such as DNA that increases inflammation or the risk of cancer. This is a critical fact discussed further in Chapter 6.

In evolution, epigenetic enhancement of inflammation is beneficial during an increased pathogen presence in the environment. For example, viral or bacterial attacks can increase inflammation in parents, causing an epigenetic enhancement of their inflammatory responses, which then transfers to their future children.

The children are then born with a stronger inflammatory response that is better at destroying the pathogen still in the environment. This better response increases survival chances. Research notes how “parental experience with parasites and pathogens can lead to increased offspring resistance to infection, through a process known as transgenerational immune priming (TGIP) (1).”

One reason for an epigenetic ability is how quickly the changes occur. Researchers note that the rate of epigenetic changes “is estimated to be substantially higher than the genetic mutation rate” and how this higher rate enables “survival in new environments before genetic adaptation evolves (2).” Rapid adjustments to the environment give epigenetic changes a strong survival advantage.

Methylation, discussed in chapter 3, creates many of the epigenetic changes. Interestingly, “DNA methylation is important in the regulation of inflammatory genes (3).” There is also an association between hypomethylation of the Toll-like receptor 2 (TLR2) promoter and an elevated pro-inflammatory response (3). Other researchers found mice fed a western diet had an enhancement of toll-like receptor responses, indicating “a primed cell state (4).” They also noticed these epigenetic changes persisted even after the mice shifted back to the control diet (4).

Others also noticed epigenetic changes “are enriched for immune response pathways, and can implicate genes not directly identified” by genome-wide association studies alone (5). This difference is important because, depending on the type of genetic research, these epigenetic changes are invisible. The same researchers also note how other studies implicate epigenetic changes to immune function in ASD (5).

Furthermore, other researchers remark how there is:

“converging evidence of a multidirectional interaction between immune system activation in the mother during pregnancy and epigenetic regulation in the brain of the fetus that may cooperate to produce an autistic phenotype. This interaction includes immune factor-induced changes in epigenetic signatures in the brain, dysregulation of epigenetic modifications specifically in genomic regions that encode immune functions, and aberrant epigenetic regulation of microglia. Overall, the interaction between immune system activation in the mother and the subsequent epigenetic dysregulation in the developing fetal brain may be a main consideration for the environmental factors that cause autism (6).”

Likely, the amount of inflammatory food and pollution in the environment causes inflammation so much that the epigenetic changes excessively raise inflammation. The enhancement of the inflammatory response in the womb disrupts neuron network formation, affecting the risk of ASD.

In an ASD child, epigenetic changes to genes that affect the immune response may also increase the sensitivity to many different sources of inflammation. This may lead to a lot of food sensitivities and being easily stressed by the outside environment.

When incorrect nutrition mixes with the modern polluted environment, then this causes the epigenetic changes to excessively increase inflammation, further depleting the body of antioxidant defenses. This depletion of defenses and enhanced inflammation causes some families to be much more vulnerable to sources of inflammation, such as incorrect nutrition, environmental pollution, lifestyle choices, and excessive psychological stress. These factors affect ASD risk by increasing inflammation in the womb and worsening ASD symptoms at any point in life.

Epigenetically enhanced inflammation is the reason that health conditions are more common in families that have an ASD child. For example, research found the autoimmune conditions rheumatoid arthritis and celiac disease occur more frequently in those families (7) (8).

ASD people are often born with a sensitive inflammatory system because the parents were already experiencing an excessive amount of inflammation. Since inflammation and epigenetic changes tend to increase with age, this is the reason older parents have a higher risk of having an ASD child. There is a discussion of age as a risk factor in Chapter 9.

Epigenetically enhanced inflammation and accumulation of inflammatory damage in some families explains why ASD appears to be genetic, despite there being no specific gene that causes a significant number of ASDs. Research has not discovered a single gene that explains more than 1% of ASD (9).

This is an important point because, currently, millions of research dollars are poorly spent searching for a genetic cause. Redirecting this money to epigenetic, nutritional, and environmental factors will get results and help more people.

Unfortunately, epigenetically enhanced inflammation is harmful when it is combined with the continual sources of inflammation in modern society. Unlike a pathogen, an enhanced response cannot stop sources of inflammation, such as pollution, refined carbohydrates, and sustained psychological stress. Combating these sources is not the design of the body because they were not a problem in our evolutionary history. The body is an elegant machine, but there are multiple factors in modern society that are not compatible with maintaining good health.

Although coming from an epigenetically enhanced family raises susceptibility, inflammation can still negatively impact someone without this type of family. The difference is someone without an enhanced inflammatory response can tolerate more inflammatory sources before the body becomes overwhelmed.

Inflammation alters many different genes epigenetically without a definite pattern. There are extreme differences in epigenetic changes, but they often increase the inflammatory response. The many various inflammatory effects and its epigenetic changes explain why ASD has such a wide spectrum.

If families of an ASD child already experience enhanced inflammation, then there may be relatives in the family that have health conditions associated with inflammation, such as autoimmune diseases. Multiple researchers note there are links between autoimmune diseases and increased inflammation (10) (11) (12).

In agreement with this concept, research found relatives of ASD children were more likely to have an autoimmune disease (13). Also, reviews found an increased chance of ASD occurrence if relatives had autoimmune diseases (14) (15).

Interestingly, some maternal antibodies may accurately predict the risk of having an ASD child (16). Research notes these antibodies may affect fetal development (17).

These studies indicate the involvement of autoimmunity, often caused by inflammation. Considering this and other information in this book, then understanding the factors that increase inflammation is likely the secret to solving the autism mystery.

However, the current trend of technology-driven science is to seek specific genes to find the cause of ASD. The fact that identical twins have an increased risk of both being autistic strongly affects this focus on genetics. Research found the chance of both twins being ASD was 31% for fraternal twins and 88% for identical twins (18). While other research, using a strict definition of ASD, found the rate to be about 60% for identical twins of the same sex (19).

However, twin studies are not an accurate measurement of genetic impact. Twins share not only genetic material but also intrauterine environments (20). Researchers note the rate of identical twins sharing a placenta is 60% (21). The researchers also note how “animal studies support the point that two-thirds of” identical twins “share the same placenta, which means that they are sharing key environmental factors” not shared by most fraternal twins (21).

If more than one placenta is in the womb, then the mother’s body may better control the damage in one placenta to increase the chance of survival for at least one of her children. Environmental problems can negatively affect one placenta much more than the other. This placenta difference explains why fraternal twins are less likely to both be autistic than twins that share the same placenta.

To further support of a greater environmental impact are a few observations.

The first observation is identical twins have significant variation in how ASD affects them (22). Also, there are a lot of epigenetic differences between identical twins (23). This is because reactive oxygen species change the epigenetic arrangements differently in each person.

The second observation is the differences in cerebellar morphometry in identical ASD twins (24). This variance occurs because of the different ways inflammation affects individuals.

The third observation is a single gene may only explain 1% of ASD (9). This is an incredible fact that really should shift ASD research money away from genetics.

The fourth observation is reactive oxygen species cause many genetic mutations (25) (26) (27) (28).

This is a critical point.

Beyond epigenetic changes, reactive oxygen species can cause DNA mutations. This means environmental and lifestyle factors can be the original cause of many genetic health conditions.

Inflammation also affects the ability to repair DNA copy errors. This is because methylation inefficiency limits the DNA repair activities. As discussed in Chapter 3, inflammation can cause methylation inefficiency.

These observations mean that the obsessive focus on ASD genetics is incorrect. The more likely causes of ASD and many other health conditions are nutritional, environmental, and lifestyle factors that lead to excessive reactive oxygen species generation.

Of course, research does find a few associations between genetics and ASD, but a major cause of those variants is DNA damage from reactive oxygen species. In addition, other genetic problems, such as copy errors, are often a result of reduced genome stability caused by methylation inefficiency, which itself is frequently a result of reactive oxygen species inhibiting methylation cycle enzymes.

Therefore, factors that increase inflammation may be the main cause of many different health conditions, including conditions with well-established genetic problems, like Fragile X, cystic fibrosis, and Huntington’s disease. For example, many generations ago an ancestor could have gotten the genetic condition from environmental factors and then passed those genes on to future generations.

Genetic researchers need to frequently ask the following questions:

What factors increase the risk?

What is causing genetic changes?

Do the genetic changes have a useful purpose?

How does inflammation affect this pattern?

Genetic alterations may often be the middleman between inflammation and many health effects. As an analogy, a lightbulb emits light, but electricity is the source of the light. Redirecting research money away from genes and towards environmental, nutritional, and lifestyle factors will lead to a significantly better return on investment and help many people.