Autism Rising: Autism Rates Higher Near Toxic Dump Sites

The ideologically based belief that autism is entirely genetic has been taking a beating in the past few years as an Autism Research Paradigm Shift has been taking place which focuses more attention on the possible environmental factors involved in causing autism disorders. And the evidence of possible environmental causes or triggers of autism disorders continues to accumulate.

The UC Davis Mind Institute study is a recent highlight of this shift towards open examination of environmental triggers and factors contributing to the increasing diagnoses of autism disorders. The The Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research - January 26, 2009 essentially codified the Autism Research Paradigm Shift with numerous elements of its Strategic Plan emphasizing possible environmental contributors and causes of autism disorders.

Now Catherine DeSoto has published a correlational study, Ockman's Razor and Autism: The case for developmental neurotoxins contributing to a disease of neurodevelopment, at Neurotoxicology doi:10.1016/j.neuro.2009.03.003 which finds that:

"within the state with the highest rate of ASD, the rate is higher for schools near EPA Superfund sites, t (332) = 3.84, p = .0001. The reasons for the rise in diagnoses likely involve genetically predisposed individuals being exposed to various environmental triggers at higher rates than in past generations.

The study is the subject of a synopsis by Heather Patisaul, Ph.D. of North Carolina State University, at Environmental Health News. Ms Patisaul explains that the Superfund sites frequently contain such pollutants as chloroethelyenes, benzene and metals (lead, mercury, cadmium, chormium, arsenic). She reports that the study found autism rates signficantly higher near the toxic Superfund Sites:

Rates of the disorder were one and a half times higher in the districts within 10 miles of the toxic sites. That translates into 1 child in 92 in districts closer to the sites compared to 1 child in 132 in the districts farther away. Schools within a 20-mile radius of Superfund sites had similar autism trends as the schools with 10 miles of the sites.

Ms Patisaul cautions that correlational studies such as this might first identify possible causal relationships but will require further information to verify any such association. Hopefully the studies necessary to verify or refute possible connections and causes will be conducted without unecessary delay.

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Environmental Causes of Autism - It Is Time To Get The Research Done

The new UC Davis Mind Institute study indicating the likelihood of environmental factors in the dramatic increases in autism cases in California is a step forward in the still developing autism research paradigm shift that investigates autism disorders and their causes from the perspective that autism is caused by a combination of environmental influence and genetic vulnerabilities:

Autism research is poised for another paradigm shift, from an irreversible condition to a treatable disease. In the revolutionary paradigm, autism is not a rare disorder with a constant rate but frequent condition with a rising incidence. It is a combination of environmental influence and genetic vulnerabilities. It is both preventable and treatable, not by any one method but by a combination of behavioral and biomedical approaches. Autistic kids are not defective, they are sick but otherwise normal kids, and thus, recoverable. 

University of Minnesota, Press Release, July 2007

The move to a combined environmental-genetic research model seems to be long overdue. The vaccine-autism controversy may well have pushed public authorities away from possible environmental causes of autism generally but it is difficult to understand why anyone ever assumed that autism is entirely genetically determined. In a December 2007 interview piece published on TimesOnLine, Freedom of Expression, Professor Simon Baron-Cohen made the following salient observiation:

Studies of twins have established that it is not 100 per cent genetic, since even among identical twins, when one has autism, the likelihood of both twins having autism is only about 60 per cent. This means there must also be an environmental component, but what it is remains unknown. 

The vaccine-autism controversies have generated entrenched positions and ideologies on all sides of those controversies.  One of the unfortunate tendencies has been a tendency to berate and ridicule any mention of possible environmental causes of autism disorders. Another has been a focus on genetic research to the near exclusion of environmental factors.  That has begun to change, as called for in the University of Minnesota 2007 press release but the change is not as fast as it could be.  

The vaccines we give children still contain the mercury based preservative thimerosal, according to the FDA web site and children are exposed to a variety of toxic materials in toys and jewelry including mercury, lead, and arsenic.  If specific environmental factors are causing or contributing to autism, whether in isolation, or in concert, then preventative measures can be taken and research into curing autism can, and should,  incorporate those factors.

It is time to drop the rigid, ideological belief that autism is 100% genetic and get the environmental research done to help our children.

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Autism Rising - UC Davis Mind Institute Study Points To Environmental Factors

Although Classics Professor Kristina Chew, ASAN co-founder Dora Raymaker, and the once progressive Change.org have decreed that autism is most likely entirely genetic, with no environmental contributing factors, recent research says otherwise. The UC Davis MIND Institute has published a news release of a study indicating that the dramatic rise in California autism cases probably arises from environmental factors. The news release also calls for an autism research paradigm shift from simplistic focus on genetic causes of autism to an examination of both genetic and environmental factors. ... with the funding necessary to fully implement the shift. In fact UC Davis Mind Institute has already been a leader in this autism research paradigm shift with its CHARGE program, a major epidemiological study investigating environmental factors and gene-environment interactions in autism disorders.

January 7, 2009 (SACRAMENTO, Calif.) — A study by researchers at the UC Davis M.I.N.D. Institute has found that the seven- to eight-fold increase in the number children born in California with autism since 1990 cannot be explained by either changes in how the condition is diagnosed or counted — and the trend shows no sign of abating.

Published in the January 2009 issue of the journal Epidemiology, results from the study also suggest that research should shift from genetics to the host of chemicals and infectious microbes in the environment that are likely at the root of changes in the neurodevelopment of California’s children.

“It’s time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California,” said UC Davis M.I.N.D. Institute researcher Irva Hertz-Picciotto, a professor of environmental and occupational health and epidemiology and an internationally respected autism researcher. .... Hertz-Picciotto said that the study is a clarion call to researchers and policy makers who have focused attention and money on understanding the genetic components of autism. She said that the rise in cases of autism in California cannot be attributed to the state’s increasingly diverse population because the disorder affects ethnic groups at fairly similar rates.

...

“Right now, about 10 to 20 times more research dollars are spent on studies of the genetic causes of autism than on environmental ones. We need to even out the funding,” Hertz-Picciotto said.

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"MARBLES" - Rare Study Examines Environmental Factors In Autism Disorders

MARBLES, Markers of Autism Risk in Babies - Learning Early Signs, is a rarity. The study being conducted by UC Davis researcher Irva Hertz-Picciotto is looking at possible environmental triggers for autism.

The Autism Knowledge Revolution advances almost daily with announcements of genetic studies and breakthroughs in understanding genetic causes or bases for autism spectrum disorders. But there seem to be fewer studies focusing on possible environmental factors.

The News10/KXTV report quotes Ms. Hertz-Picciotto:

"Autism is very clearly not a single cause type of condition. It's got to be multiple factors," said Hertz-Picciotto, who hopes her study will reveal environmental factors that combined with genetics can trigger autism.

"We expect to find a number of different exposures that affect neurodevelopment and may be related to autism mildly, small increments of risk, for each exposure, but there may be multiple exposures," said Hertz-Picciotto.

To date the study involves 100 women and 59 babies who are being followed for a three year period. Blood samples will be withdrawn at regular periods.

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More On Autism and Maternal IgG Antibodies From the UC Davis MIND Institute

The UC Davis Mind Institute has issued a press release elaborating on its new study on maternal IgG antibodies and autism which found that "antibodies in the blood of mothers of children with autism bind to fetal brain cells, potentially interrupting healthy brain development" and that "the reaction was most common in mothers of children with the regressive form of autism"

Some cases of autism may be traced to the immune system of mothers during pregnancy

UC-Davis discovery could lead to prenatal identification and prevention

(SACRAMENTO, Calif.) – New research from the UC Davis M.I.N.D. Institute and Center for Children’s Environmental Health has found that antibodies in the blood of mothers of children with autism bind to fetal brain cells, potentially interrupting healthy brain development. The study authors also found that the reaction was most common in mothers of children with the regressive form of autism, which occurs when a period of typical development is followed by loss of social and/or language skills. The findings, to be published in the March 2008 issue of Neurotoxicology, raise the possibility that the transfer of maternal antibodies during pregnancy is a risk factor for autism and, at some point, that a prenatal test and treatment could prevent the disorder for some children.

“While a growing body of research is dedicated to finding distinctions in the immune systems of children with autism, this is one of the first studies to identify immunological factors in mothers that could be linked to autism in the very earliest stages of life,” said Judy Van de Water, senior author of the study and professor of rheumatology, allergy and clinical immunology. “Our results should lead to more research on the prenatal environment and the onset of autism. We are also optimistic that in the future a prenatal test and therapeutic intervention preventing IgG exposure during pregnancy could protect some children from ever getting autism.”

Van de Water and her team began their research with blood samples from 123 mothers – 61 whose children have autism and 62 whose children are typically developing. They isolated IgG antibodies from the samples then exposed the antibody to fetal brain tissue by western blot analysis, which detects antibody reactivity to proteins. The outcome revealed a highly specific reactivity pattern to two fetal brain proteins in seven of the 61 samples from the autism group, six of which were from mothers of children who had regressive autism. None of the IgG samples from mothers in the control group produced this same result.

“We’re not entirely sure why the IgG response against fetal brain proteins was so specific for later onset autism,” said Van de Water. “It’s possible that early exposure to maternal antibodies sets in motion a biological path to autism with the behavioral outcomes not apparent until much later. It’s also possible that an environmental exposure sometime after birth could be required to set this process in motion. We are hopeful that this study will help build our understanding of the foundations of the regressive form of the disorder.”

Characteristic features of autism – social deficits, language impairments and limited, repetitive behaviors – are often clear early in an affected child’s life. Other children seem to progress normally until 12-to-24 months of age, when developmental milestones disappear. These distinct pathways have led clinicians to identify autism as one of two types – early onset or regressive – potentially with distinct causes and disease processes.

IgG antibodies are responsible for long-term immune system responses to infection, but they can also contribute to autoimmune diseases such as arthritis, multiple sclerosis and lupus. IgG also crosses the placenta in order to provide key immune system protectants to a growing fetus and newborn child, which is a key reason why Van de Water decided to investigate the role of IgG as a potential factor in autism.

Van de Water next wants to know if IgG in women during the time of their pregnancies produces the same response to fetal brain proteins. Women in the current study were two-to-five years beyond childbirth. She will now conduct the same study with women who are pregnant and already have a child with autism, because such women are much more likely to have another child with the disorder.

“If women in this next phase of the study give birth to a child eventually diagnosed with autism, blood analyses from all stages of her pregnancy will give us a clear picture of the immune system factors that were in play during gestation and could have altered her child’s neurodevelopment,” Van de Water said.

Other key next steps are to identify the specific proteins targeted by autism-specific maternal antibodies and their role in neurodevelopment and to determine whether or not exposure to maternal IgG during pregnancy leads to behavioral or social distinctions in offspring. Animal model studies are now under way to help answer these questions.

“Our outcome leads autism science in many new and exciting directions,” said Daniel Braunschweig, pre-doctoral fellow of immunology in the Van de Water lab, lead author of the current study and recent recipient of an Autism Speaks mentor fellowship to further pursue this research. “We now know we should be looking for the clues to the onset and pathology of autism much earlier than was initially assumed. Future studies should consider the immune system interactions between mother and child as a focal point in creating greater understanding of, and eventually finding effective preventions for, this complex neurodevelopmental disorder.”

“This finding is important because it provides important clues about the potential maternal contributions to autism risk in a subset of children who may develop autism,” said Isaac Pessah, director of the UC Davis Center for Children’s Environmental Health and professor of molecular biosciences. “We’re determined to find out what causes autism. Studies conducted in the Van de Water lab are giving us valuable insights as to when and where in the developmental process we should be looking for those causes.”

“We’re very interested in understanding the underlying causes of autism,” said Cindy Lawler, scientific program director at the National Institute of Environmental Health Sciences. “This finding, in combination with other new research findings coming from NIH-funded studies, demonstrates the complexity of this disorder and underscores the importance of understanding how the mother’s immune system can influence early brain development.”

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The study, “Maternally Derived Antibodies Specific for Fetal Brain Proteins,” was funded by the National Institutes of Environmental Health Sciences, the U.S. Environmental Protection Agency and the M.I.N.D. Institute. A copy can be requested from newsroom@elsevier.com or downloaded at www.sciencedirect.com.

The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center that brings together clinicians, scientists, parents and educators for research on causes, treatments, preventions and cures for autism, fragile X syndrome, Tourette’s syndrome, attention-deficit/hyperactivity disorder and other neurodevelopmental disorders. For more information, visit www.mindinstitute.org.

The UC Davis Center for Children’s Environmental Health and Disease Prevention is a multi-disciplinary research effort established to examine how toxic chemicals may influence the development of autism in children. Toward that goal, the center is conducting two large-scale research projects: the Childhood Autism Risks from Genetics and the Environment (CHARGE) study and Markers of Autism Risk in Babies—Learning Early Signs (MARBLES) study. For more information, visit www.vetmed.ucdavis.edu/cceh.

Editor’s note: B-roll of blood sample processing for immunological studies of autism in the Van de Water lab is available on request.

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Autism and Potential Environmental Causes - Maternal Antibody IgG

Maternal IgG (an antibody) may be a factor in causing autism according to a study conducted by researchers from the UC-Davis MIND Institute. The study report, Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism, by researchers Loren A. Martin, Paul Ashwood, Daniel Braunschweig, Maricel Cabanlit, Judy Van de Water, and David G. Amarala, is currently an article in press in Brain, Behavior, and Immunity and the abstract is available on line from Science Direct. The report notes an emerging consensus that Autism Spectrum Disorders have multiple etiologies (causes or origins) and indicates that the study tested the proposition that one cause of ASD may be exposure of the fetal brain to maternal autoantibodies during pregnancy. The study essentially involved comparing a group of rhesus monkeys exposed to human IgG collected from mothers of multiple children with ASDs to rhesus monkeys exposed to IgG from mothers of multiple typically developing children and to a further control group of untreated rhesus monkeys.

As described in the Science Direct abstract:

"four rhesus monkeys were exposed prenatally to human IgG collected from mothers of multiple children diagnosed with ASD. Four control rhesus monkeys were exposed to human IgG collected from mothers of multiple typically developing children. Five additional monkeys were untreated controls. Monkeys were observed in a variety of behavioral paradigms involving unique social situations. Behaviors were scored by trained observers and overall activity was monitored with actimeters. Rhesus monkeys gestationally exposed to IgG class antibodies from mothers of children with ASD consistently demonstrated increased whole-body stereotypies across multiple testing paradigms. These monkeys were also hyperactive compared to controls. Treatment with IgG purified from mothers of typically developing children did not induce stereotypical or hyperactive behaviors. These findings support the potential for an autoimmune etiology in a subgroup of patients with neurodevelopmental disorders. This research raises the prospect of prenatal evaluation for neurodevelopmental risk factors and the potential for preventative therapeutics."

A helpful definition of IgG can be found at the Dalhousie University Faculty of Medicine Immunology Bookcase web site. The definition points out that IgG is the most abundant form of antibody in the blood, that it is able to leave the blood stream and enter tissues and that it is the only form of antibody to pass the placental barrier:

IgG is the most abundant form (class) of antibody in the blood (serum concentration is 13 mg/ml !). There are four subclasses of IgG which are all monomeric and they usually have a very high affinity for antigen. Unlike IgM, IgG is able to leave the blood stream and enter tissues.

IgG is also the only class of antibody to pass the placental barrier. Therefore IgG provides the only antibody protection for newborns until their own immune system is able to contribute to antibody production.

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Autism, Genetics and Environment - Study Finds Autism Immune System Link

A study reported in the January 2008 issue of Genomics, Gene expression changes in children with autism, has found that a group of genes with known links to natural-killer cells, that attack viruses, bacteria and malignancies, are expressed at high levels in the blood of children with autism when compared to children without the disorder. The study also found gene expression distinctions in children with early onset and regressive autism. The study is summarized in a digestible format on the UC Newsroom article Researchers identify gene expression profile distinctions in children with autism. Comments by the senior researcher Frank Sharp M.D. clinical neurologist, neuroscientist, and professor, department of neurology, school of medicine, indicate that the findings suggest a possible environmental role in the development of autism disorders:

"What we found were 11 specific genes with expression levels that were significantly higher in the blood of children with autism when compared to the blood of typically developing children," said Frank Sharp, senior author of the study and professor of neurology with the M.I.N.D. Institute.

"Those 11 genes are all known to be expressed by natural-killer cells, which are cells in the immune system necessary for mounting a defense against infected cells. We were surprised by our results because we were not looking for these particular genes. And while a number of studies have shown immune system dysregulation to be an important factor in autism, ours is one of the first to implicate these particular cells."

...

"What we are seeing can reflect something in the environment that is triggering the activation of these genes or something genetic that the children have from the time they were conceived," Sharp explained. "Such an immune response could be caused by exposure to a virus, another infectious agent or even a toxin.

Another possibility is that these changes represent a genetic susceptibility factor that predisposes children to autism when they are exposed to some environmental factor." He added that the current study also does not identify whether or not the natural-killer cells are functioning abnormally, which further work by M.I.N.D. Institute immunologists will reveal. "If the natural-killer cells are dysfunctional, this might mean that they cannot rid a pregnant mother, fetus or newborn of an infection, which could contribute to autism."

The study is also featured in an article by Carrie Peyton Dahlberg at sacbee.com which features several interesting comments by Dr. Jeffrey Gregg, director of molecular diagnostics for the UC Davis Medical Center who was also involved in the study. It is pointed out that both similarities and differences were found between the early onset and regression autism cases:

Children with that "regressive" autism had nearly 500 genes that were activated differently than children with "early onset" autism, Gregg and his colleagues found after examining blood samples from 61 children.

"That would suggest that those two groups are very different … and may have totally different underlying pathology," Gregg said.

Both groups, though, as well as other children with a range of symptoms called autism spectrum disorder, shared the 11 strongly expressed genes that control natural killer immune cells.

Dr. David Amaral, the UC Davis MIND Institute's research director suggested that much remains to be learned about how the genetic and environmental factors giving rise to autism interact:

It is still unclear how early those differences emerge, but other MIND Institute researchers are looking at immune differences in mothers' bloodstreams that might be predictive for having a child with autism, said Dr. David Amaral, the institute's research director.

"Things are moving really, really fast now," Amaral said, with scientists around the country working to understand the relationship of genetic and environmental factors that may underlie autism.

It seems clear from this study that environmental factors can not be ruled out in trying to understand the causes -- and potential treatments for autism. Some of the rhetoric which dismisses all genetic or all environmental factors appears to be ill founded. The Autism Knowledge Revolution is being carried out by researchers and scientists in relevant medical fields and the knowledge they are gaining appears to point to both genetics and environment as being involved in the development of autism.

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