Autism and the Environment 201
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Introduction
What is the Purpose of This Curriculum?
This curriculum will introduce you to areas of importance in Children’s Environmental Health, with a particular focus on neurodevelopment and Autism Spectrum Disorders. While there are no certain connections between environmental exposures and the symptoms that comprise ASDs, the dramatic rise in the cases of these disorders point to a potential role for environmental factors in their development. By understanding the broad issues in this field, parents, educators, physicians, policymakers, and individuals with autism will be in a position for three further actions: 1) Making informed decisions about their daily environmental exposures; 2) Expressing their concerns on the topic to their elected representatives in government; and 3) Engaging in further study of the topic. In addition to this curriculum, we have provided lists of peer-reviewed journal articles and Internet links that will allow for this further study.
Defining Environmental Health
The study of Environmental Health works to identify how the environment, in combination with genes, can lead to the development of disease. There are many different processes that take place within the human body. It goes without saying that the human being is a complicated organism. Our genes provide the instructions that allow these processes to happen, but we are also in constant contact with out environment. This environment includes all things external to our bodies, including heat, noise, pollution, infections, and many other factors. Some of the chemical entities that we are exposed to, especially the many in recent times that are of human origin, are said to be bioactive, that is, they interact with the chemical processes already going on in our bodies, those governed by our genes. If these environmental chemicals interfere with the delicately balanced processes that govern our bodies, this can have serious consequences. The more we can understand these potential interactions, the more information we will have make smart decisions as a society to ensure that they are avoided.
Detoxification Basics
A New Model of Autism
Individual Susceptibility
Children’s Susceptibilities
Children are at greater risk for environmental exposure because of both their different activity patterns and their developing systems. Infants spend much of their time close to the floor where heavy air pollutants settle and where they are in contact with dust and its potentially harmful components. Their body size means that they ingest far more food per pound than adults, concentrating the effects of any foodborne exposures. Their defense systems are also immature, making it harder for them to fend off the negative effects of any such exposures. Most importantly, many of their organs, including their brains, are still developing and may be particularly sensitive to toxic insult.
The Developing Brain
The human brain begins as a crest of fewer than a dozen cells and develops into one of the most complex structures known to science. Much of this occurs during the 9 months of gestation, but complex processes continue through early childhood and adolescence. This must occur with stunning specificity and coordination, especially for the most high-order functions of the organ to perform correctly. There are many critical junctures that are particular sensitive to toxic insult, without parallel in the mature brain or in other organs. If such processes proceed improperly or fail to occur, there is often little opportunity to return in the developmental course to correct the problem.
The Developing Immune and Detoxification Systems
The body’s systems or protecting against infectious invaders and for eliminating toxic compounds are not fully functional at birth and must develop through early childhood. This puts infants and young children at particular risk for a
Blood-Brain Barrier
The brain is a very sensitive and delicate piece of machinery. In order for it to work properly, its internal environment must be very carefully maintained. For this we have the Blood-Brain Barrier. It’s not one single barrier, but runs along the lining of all of the blood vessels in the brain, making this lining much tougher and tighter than in other parts of the body (100x tighter) and is formed by living cells sort of in the form of a zipper to make it extra tight. There is concern that some environmental pollutants may increase the porousity of this barrier, exposing the brain to potentially damaging infection and other pernicious factors.
Impact of Early Childhood Infections and Illness
Anecdotal reports indicate a connection between early childhood illness and infection and the onset of autistic symptoms. A recent review of medical records indicates this percieved association may not in fact be real, at least in when considering the autistic population as a monolithic whole. Nonetheless, interest persists as to potential mechanisms that may account for such a relationship in at least some individuals. Plausible biologic explanations include: systemic inflammation comprimising the blood-brain barriers; impaired NK cell response; and general immune imbalance towards as T2 phenotype, among others. The basics of these concepts are introduced here.
Nutrition
Many of the body’s processes require the participation of certain compounds that cannot be manufactured internally and thus must be obtained from the diet. These are termed ‘essential nutrients’. A deficiency of essential nutrients can impact some of the same pathways as toxic exposures and a cooccurance of deficiency and exposure can have compounding effects. As well, the body relies on a class of nutrients known as antioxidants to counteract the naturally prooxidant nature of certain environmental agents, especially heavy metals. These general topics are introduced here.
Chemical Regulation in the United States
A comprehensive summary of legislation related to the regulation of chemicals in the United States is presented in a 2005 Environmental Health Perspecives piece by X, available electronically here. The primary mechanism for this regulation is the Toxic Substances Control Act, passed by the United States Congress in 1976. In the intervening three decades, it has been amended only minimally, to include regulation of radon, asbestos, and lead. Legislation currently under consideration, known as the Kids Safe Chemicals Act, would reevaluate the regulatory approach to such potentially toxic chemicals, undertaken a precautionary approach. This is in line with recent changes in the European Union, under the REACH program (Registration, Evaluation, Authorisation and restriction of CHemical substances). This new law entered into force in June 2007 and is reviewed here.
A Push for Developmental Neurotox Testing
More than 80,000 chemicals are registered for commercial use with the US Environmental Protection Agency. Of these, most have not been evaluated for neurodevelopmental toxicity. History shows that many chemicals in wide use originally suspected to be safe, have later been found to be toxic even at small doses, often causing symptoms that are subclinical and thus not noticed by medical professionals. In 2006, Phillip Grandjean and Phillip Landrigan, eminent physicians and researchers at the forefront of the environmental health debate, published a review on this subject in the British medical journal The Lancet. In addition to reviewing the history and current state of science of developmental neurotoxicity, they make a case for increased testing and regulation of industrial chemicals with a focus on a precautionary approach. This article is available online for a moderate fee, and is both valuable reading and an important resource to put in the hands of policymakers.
Current Environmental Health Research in Autism
A number of research projects are currently underway to investigate the potential role of environmental exposures in ASDs. These include: the Autism Birth Cohort (ABC) at the
Norwegian Institute of Public Health and Columbia School of Public Health; Childhood Autism Risks from Genetics and Environment (CHARGE) and Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) both at UC Davis; Study to Explore Early Development (SEED) - Kaiser Permanente (CA), Johns Hopkins University, University of North Carolina, University of Pennsilvania, and University of Colorado; and the Early Autism Risk Longitudinal Investigation (EARLI). These are reviewed in a recent essay by Micheal Szpir in Environmental Health Perspectives.
Precautionary Principle
The Precautionary Princliple is not a new idea. For many generations, we have recognized that when there is a certain likelyhood that an action or policy may have negative consequences, we should defer to a precautionary approach, achieving some high level of certainy that such action is in fact safe before proceeding. Unfortunately, this had not been the course taken with regard to the regulation of chemical manufacturing in this country in recent decades. In response, in 1998, a group of scientists, ethicists, lawyers, and activists convened at the Wingspread Conference in Madison, WI. Their consensus statement included the prescription: "When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context the proponent of an activity, rather than the public, should bear the burden of proof…”
Epidemiology
Here is presented an introduction to the basic concepts of Epidemiology. Among the most important messages to take from this introduction is that epidemilogy is not in a position to prove causality, only to show that observed relationships and associations that occur for reasons other than chance. As well, researchers must excercise caution in designing epidemiological studies so that they do not introduce inintended biases into their analysis. These can be biases that influence the outcome in either of two directions, towards both false-positive and false-negative conclusions.
Studies on Spatial and Demographic Patterns of Autism
Included here are abstracts from several studies showing associations between particular environmental exposures and increased incidence of ASDs.
In Texas, Raymond Palmer and colleagues (2006, 2008) have shown an association between environmental mercury release from coal-burning power plants and other industrial facilities and both overall special education rates and rates of autism. The association becomes stronger as distance to the industrial site decreases.
In the San Francisco Bay Area, Gayle Windham and colleagues (2006) investigated a cohort of children born in 1994, finding that neighborhoods with high levels of certain airborne chlorinated pollutants and heavy metals had higher rates of ASDs. Chemicals implicated included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride.
Three recent investigations have linked pesticide exposure to increased rates of ASDs, though each study implicated a different pesticide. In Northern Manhattan, Virginia Rauh and colleagues (2006) found that children with high levels of pesticide metabolites in their blood were 6 times more likely to show ‘PDD problems’ than children with low levels. In a study of children of agricultural workers in California’s Salinas Valley, Brenda Eskenazi and colleagues (2007) found that for every ten-fold increase in the levels of blood pesticide metabolite, the rates of PDD more than doubled. In research at UC Davis, Irva Herz-Piccioto (2008) found that the use of pesticide-containing pet shampoo during pregnancy significantly increased the chance of the unborn child later developing an ASD.
Genetics and Gene-Environment Interactions
Here is presented an introduction to the interaction between genes and the environment in the development of complex conditions such as ASD. Such interaction can take several forms: 1) Environmental chemicals can induce cells to over- or underexpress certain genes, leading to aberrations in development or functioning; 2) Similarly, chemicals can interfere with the protein products of these genes, making them more or less functional; 3) Genes responsible for the machinary of the detoxifcation system or other of the body’s defenses can be dysfunctional, making the individual more susceptible to such exposures; 4) Inherited genetic polymorphisms can impact a particular juncture of a metabolic or developmental pathway while at the same time, an environmental exposure can impact a separate but related juncture on the same pathway, resulting in more than additive effects. These several types of gene-environment interacts can also take place concurrently, compounding the problem further.
Interaction Between Gut, Immune System, and Brain
- Pollutants:
- Lead
- Mercury
- PCBs
- Pesticides
- Endocrine Disruptors
- Flame Retardants
- Plasticizers
- Antimicrobials
Historical background and potential effects on neurodevelopment are discussed for these classes of environmental pollutants.
Mixtures
While most laboratory tests on chemical toxicity center on individual exposures and their potential effects, this does not reflect a real-world scenario. In fact, as we move through our lives, we are exposed to a wide array of compounds in different times and in different combinations. Especially as some of these share similar modes of action, it is important to recognize how these combinations may have effects that are not predicted by testing of individual compounds. These effects may be additive, or their combined effects may be more than additive. As well, different exposures may be antagonistic, effectively counteracting one another. Unfortunately, the dizzying number of potential combination makes the testing of these combinations difficult, but it is an important consideration to appreciate.
| Sponsored by the John Merck Fund |
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