New studies point to environmental causes for autism

As the numbers of children with Autism Spectrum Disorder have continued to climb through the years — the latest official figures from last year show that 1 in 36, or 2.8 percent, of 8-year-olds had autism in 2020 — scientists have intensified their efforts to pinpoint a cause or causes, and new studies this past year have added to a growing belief that environmental factors play a pivotal role.

Researchers from Case Western Reserve University School of Medicine, from the University of Texas at San Antonio, and from Rowan-Virtua School of Osteopathic Medicine and Rutgers University-New Jersey Medical School have all added to an already massive body of work pointing to chemical exposures as a key contributing factor to the development of Autism Spectrum Disorder, or ASD.

ASD is a developmental disorder that can be characterized by social and communication challenges, along with limited interests and repetitive behaviors. The most recent prevalence rates in the report were based exclusively on documented ASD diagnostic statements, documented ASD special education classifications, or documented ASD ICD medical codes.

The numbers released last year — they will be updated next year — showed a 22-percent increase in prevalence from the previous reporting period when the number was 1 in 44. 

Most astonishing, those prevalence rates reflect a 320-percent increase in the disorder since 2000, when 1 in 150 8-year-olds were diagnosed with ASD. That number climbed to 1 in 88 by 2008, and to 1 in 59 in 2014.

The numbers come from the Centers for Disease Control and Prevention Autism and Developmental Disabilities Monitoring (ADDM) sites in Wisconsin, Maryland, Arizona, Arkansas, California, Georgia, Minnesota, Missouri, New Jersey, Tennessee, and Utah. The study was published in the March 23, 2023, Morbidity and Mortality Weekly Report.

For years, many public health officials insisted that the cause was almost totally genetic, despite the absence of widespread observable autism in the past. But they also had an arsenal of scientific studies on their side, albeit many with pharmaceutical company funding ties. However, through the years, the studies isolating environmental factors have also gained traction.

None of which are necessarily contradictory. In recent years a non-binary view has emerged that attributes autism to both a genetic predisposition and environmental exposures serving as triggers.

In any case, the most recent research builds on the growing body of work pointing to at least a contributing role for environmental factors, a line of thought that began to tick upward in 2010 with the publication of Dr. Dennis Kinney’s “Environmental Risk Factors for Autism,” which found increased autism risks associated with preconceptual exposures to such substances as mercury, cadmium, nickel, vinyl chloride, and trichloroethylene. 

In 2014, a study by Dr. Irva Hertz-Picciotto of the University of California-Davis found that pregnant women who lived in close proximity to fields and farms where chemical pesticides were applied experienced a two-thirds increased risk of having a child with autism or other developmental delay.

Such papers proliferated, and even a 2015 paper published in JAMA Psychiatry that concluded that autism was almost entirely genetic couldn’t eliminate environmental factors.

Just recently three new studies have added to the tome.

It’s the chemicals, stupid

A recently released study from Case Western Reserve University School of Medicine indicates that chemicals found in a broad range of household items harms specialized brain cells. The chemicals, found in everything from furniture and electronics to hair care products and hand disinfectants, might be linked to neurological diseases like multiple sclerosis and autism, the study warned, urging more research.

Specifically, the study, published in the journal Nature Neuroscience, uncovered evidence that common home products affect the oligodendrocytes, a specialized brain cell that generates protective insulation around nerve cells.

“Loss of oligodendrocytes underlies multiple sclerosis and other neurological diseases,” Dr. Paul Tesar, the director of the Institute for Glial Sciences at the School of Medicine, said in releasing the study. “We now show that specific chemicals in consumer products can directly harm oligodendrocytes, representing a previously unrecognized risk factor for neurological disease.” 

The researchers pored over 1,823 chemicals that people routinely come in contact with, discovering that two classes of chemicals selectively damaged the oligodendrocytes: organophosphate flame retardants and quaternary ammonium compounds.

Quaternary ammonium compounds are frequently found in personal-care products and disinfectants that have been in greater demand since the pandemic.

“Quaternary compounds are common in personal care products, pharmaceuticals, and anti-static agents,” the study stated. “Their prevalent use in disinfectants, including more than half of EPA-registered products for eliminating SARS-CoV-2, is a likely cause of increased human exposure, demonstrated by the doubling in blood levels of some quaternary ammonium compounds since before the Covid-19 pandemic.”

Meanwhile, organophosphate flame retardants often show up in furniture and electronics and in such products as dyes, varnishes, textiles, adhesives, and synthetic resins.

“The pervasive use of organophosphate flame retardants has contaminated the environment and increased human exposure, demonstrated by the detection of these chemicals in human blood, urine, breast milk, and cerebrospinal fluid,” the study stated. “We show that the organophosphate flame retardant TDCIPP arrests the development of mouse oligodendrocytes and inhibits oligodendrocyte generation in human cortical organoids at concentrations similar to estimated blood concentrations in children.”

For example, the researchers explained, previous human epidemiological studies that evaluate prenatal exposure to TDCIPP have identified associations between maternal exposure and delayed cognitive development, but the researchers asked, given the prolonged period of oligodendrogenesis and myelination after birth, whether postnatal neurodevelopment would be impacted by organophosphate flame retardant exposure throughout childhood and adolescence. 

The researchers analyzed the CDC’s 2017-2018 data to identify associations between childhood exposure to organophosphate flame retardants and abnormal neurodevelopmental outcomes. 

“Our logistic regression analyses demonstrate that there are significantly increased odds ratios for children with the highest urinary BDCIPP concentrations for multiple abnormal cognitive and motor outcomes,” the study stated. “… These results indicate that children with high exposure are between 2.7 and 6 times more likely to experience adverse neurodevelopmental outcomes, providing strong evidence of a positive association between organophosphate flame retardant exposure and abnormal neurodevelopment.”

The researchers stressed that the study found a correlation but not causative proof and urged further study.

“We found that oligodendrocytes — but not other brain cells — are surprisingly vulnerable to quaternary ammonium compounds and organophosphate flame retardants,” said Erin Cohn, lead author and graduate student in the School of Medicine’s Medical Science Training Program. “Understanding human exposure to these chemicals may help explain a missing link in how some neurological diseases arise.”

BPA linked to autism, attention deficit hyperactivity disorder

In another study, published in PLOS One by researchers at Rowan-Virtua School of Osteopathic Medicine and Rutgers University-New Jersey Medical School, researchers found that children with ASD and ADHD often have a reduced ability to clear a common plastic additive, bisphenol A (BPA), from their bodies, thereby increasing their exposure to BPA.

It’s not the first study to find associations between children with autism and exposure to BPA, the researchers stated, but this study advanced the science by finding that in certain children there is a decreased efficiency in a key step involved in BPA detoxification. 

“The major pathway for BPA and DEHP excretion is via glucuronidation,” the study stated. “Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.”

But, the researchers stated, humans vary in the genetic ability to detoxify BPA and genetically susceptible individuals have more difficulty detoxifying their blood. The practical effect is to expose body tissues to BPA for increased periods of time and at higher concentrations.

“The metabolic consequence of this greater residence time in the body of the active forms of the two plasticizers is more exposure to the tissues of the two plasticizers,” the study stated. “Elevated blood levels of BPA and MEHP for children with ASD and ADHD have been reported.”

That does not necessarily prove causation, the researchers cautioned.

“However while consistent with, it does not necessarily follow that this is due to decreased glucuronidation efficiency although elevated blood concentrations are consistent with the impaired glucuronidation hypothesis because the expected result is higher blood concentrations,” the researchers wrote.

That said, they added, it is not likely to be without consequence. 

“Numerous studies have shown both function as endocrine disruptors,” the study stated. “Endocrine disruption is a very broad term that can encompass multiple metabolic processes ranging from altered gene expression to altered oxidative stress. In rodent models MEHP and BPA impede fetal growth, development, and behavior.”

For ADHD, the researchers wrote, there is direct evidence of a systemic difference in metabolism from control children. 

“The whole body protein synthesis and breakdown rates (turnover) and amino acid flux are elevated in children with ADHD and the BMR is increased,” they wrote. “Protein turnover is a systemic process accounting for about 20 percent of the BMR and directly related to energy expenditure as well as nucleotide metabolism. A difference in the whole-body protein synthesis rate will reflect underlying differences in a significant proportion of the numerous metabolic processes that lead to the synthesis and degradation of proteins.”

There is no analogous whole-body data available for ASD even though there is a very extensive literature on the association of multiple specific differences in intermediary metabolism with neurodevelopment disease which is consistent with a systemic response, the researchers observed.

Overall, the study results indicated that glucuronidation efficiencies for BPA were reduced by 11 percent for ASD compared to controls and 17 percent for ADHD.

“The compromised ability to clear such environmental pollutants from the body is the first hard biochemical evidence of what the linkage is between BPA and the development of autism or ADHD,” T. Peter Stein, the study’s lead author and a Rowan-Virtua professor of surgery, said. “We were surprised to find that ADHD shows the same defect in BPA detoxification.” 

More research is needed to determine whether autism and ADHD are developed in utero through increased exposure to the mother or to the child sometime following birth, Stein said. 

Stein also said there were likely to be other factors behind the development of autism and ADHD because the inability to effectively clear those chemicals from the blood was not present in every child with the neurodevelopmental disorders. 

“Almost certainly there are other pathways that lead to ASD and ADHD,” the study stated. “The scheme presented applies only to the plasticizer associated pathway. How important plasticizer originated neurodevelopmental disorder is in the overall occurrence of these disorders is not known, but it must account for a significant proportion or it would not have been so easy to detect in a metabolic study of moderate size such as this study.”

The team studied glucuronidation efficiency in three groups of children recruited from Rutgers-New Jersey Medical School clinics: 66 with autism, 46 with ADHD and 37 healthy children. 

The study’s co-authors are Margaret D. Schluter and Robert A. Steer at the Rowan-Virtua School of Osteopathic Medicine and Xue Ming at Rutgers University–New Jersey Medical School.

Chemical intolerance

Yet a third recent study assessed how chemical intolerance in parents could predict the risk of autism and ADHD in their children.

The study by Dr. Claudia S. Miller, Dr. Raymond Palmer, and colleagues of the University of Texas Health Science Center at San Antonio sought to replicate their 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. What they discovered was that parental avoidance of toxic exposures could help prevent those disorders.

“Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link,” the researchers stated. 

Using the internationally validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) in a population-based survey of U.S. adults, the researchers assessed symptom severity and chemical intolerance. 

“Parents were asked how many of their biological children had been diagnosed with autism and/or ADHD,” the study stated. “Parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for ADHD.”

The researchers concluded that high chemical intolerance scores among parents of children with autism, coupled with the 2021 discovery of mast cell activation as a plausible biomechanism for chemical intolerance, suggested that the survey could identify individuals at increased risk and that environmental counseling may reduce personal exposures and risk.

Further, the researchers concluded that the global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically “turning on” or “turning off” critical mast cell genes that can be transmitted transgenerationally. 

The researchers stressed the observational nature of the study and called for further research using controlled trials to confirm causality.

“This is the first-ever article in the medical literature showing that chemical intolerance in parents can predict the risk of autism and ADHD in their children, and suggests that reducing exposures prior to and during pregnancy could help prevention,” said the study’s senior author, Dr. Claudia S. Miller, professor emeritus with the Department of Family and Community Medicine at UT Health San Antonio. “Up to now, most interventions have been behavioral or medical, after a child is diagnosed.”

The study, “Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children,” was published this month in the Journal of Xenobiotics. Co-authors included Dr. Rodolfo Rincon of the Department of Family and Community Medicine at UT Health San Antonio and David Kattari, a statistician with the Marilyn Brachman Hoffman Foundation in Fort Worth, Texas.

More specifically, in 2021 Miller and colleagues discovered a strong association between chemical intolerance and “mast cells,” which they say are considered the immune system’s first responders, originating in the bone marrow and migrating to the interface between tissues and the external environment where they then reside.

When exposed to “xenobiotics,” foreign substances like chemicals and viruses, they can release thousands of inflammatory molecules called mediators, the researchers stated. That response results in allergic-like reactions, some very severe. 

“These cells can be sensitized by a single acute exposure to xenobiotics, or by repeated lower-level exposures,” they stated. “Thereafter, even low levels of those and other unrelated substances can cause the mast cells to release the mediators that can lead to inflammation and illness.”

The researchers concluded that after mast cells are sensitized, diverse xenobiotics that never bothered the person previously and do not bother most people trigger multisystem symptoms that wax and wane over time. That persistent activation and triggering of mast cells may underlie the brain inflammation in autism, the researchers assert.

“The potential role of environmental toxicants in influencing epigenetics and mast cell function is a complex and emerging area of research,” they wrote. “Acknowledging the need for further evidence, we hope this study contributes to an improved understanding of the potential role of environmental factors in the global rise of autism and ADHD.”

In 1996, Miller first proposed a two-stage disease process of initiation by exposure and then triggering of symptoms called TILT, for Toxicant-Induced Loss of Tolerance, as the mechanism behind chemical intolerance, the University of Texas observed, noting that her published papers have explored the impact of pesticides, the Gulf War, breast and other implants, 9/11, toxic molds, combustion products from fires, and indoor air pollutants in so-called “sick” homes, schools and workplaces, including the EPA’s own headquarters building in Washington, D.C.

Richard Moore is the author of “Dark State” and may be reached at richardd3d.substack.com.