I Wish I Were Far From the Madding Crowd

March 28, 2010

Environmental exposures and child development

Came across several articles in Current Opinion in Pediatrics because of a blog post on Autism and environmental chemicals: a call for caution. Unfortunately, only the abstracts are free to view.

But what these show is that medical science is beginning to look more closely at possible environmental causes of childhood diseases.  This  does not mean that environmental factors in and of themselves cause disease, but as Dr. Philip Landrigan notes, genetic factors account for only a small fraction of autism cases and do not explain key features of autism.

What causes autism? Exploring the environmental contribution

Landrigan, Philip J.  Current Opinion in Pediatrics. 22(2):219-225, April 2010. doi: 10.1097/MOP.0b013e328336eb9a

Excerpts from the abstract:

Autism is a biologically based disorder of brain development. Genetic factors – mutations, deletions, and copy number variants – are clearly implicated in causation of autism. However, they account for only a small fraction of cases, and do not easily explain key clinical and epidemiological features. This suggests that early environmental exposures also contribute. This review explores this hypothesis.

Expanded research is needed into environmental causation of autism. Children today are surrounded by thousands of synthetic chemicals. Two hundred of them are neurotoxic in adult humans, and 1000 more in laboratory models. Yet fewer than 20% of high-volume chemicals have been tested for neurodevelopmental toxicity.

Environmental exposures and development

Mattison, Donald R. Current Opinion in Pediatrics. 22(2):208-218, April 2010. doi: 10.1097/MOP.0b013e32833779bf

Excerpts from the abstract:

Summarizes recent studies exploring the relationship between paternal and maternal environmental exposures to chemicals before, at the time of and after conception to adverse developmental outcomes including preterm birth, death, structural and functional abnormalities and growth restriction.

Recent studies have demonstrated that human pregnancy and development are vulnerable to environmental exposures of the father and mother to chemical, biological and physical agents.

Whereas single genes and individual chemical exposures are responsible for some instances of adverse pregnancy outcome or developmental disease, gene-environment interactions are responsible for the majority.

Gene-environment interaction and children’s health and development

Wright, Robert O; Christiani, David. Current Opinion in Pediatrics. 22(2):197-201, April 2010. doi: 10.1097/MOP.0b013e328336ebf9

Excerpt from the abstract:

Purpose of review: A systematic approach to studying gene-environment interaction can have immediate impact on our understanding of how environmental factors induce developmental disease and toxicity and will provide biological insight for potential treatment and prevention measures.

Summary: Using a genome-wide approach, combined with prospective longitudinal measures of environmental exposure at critical developmental windows, is the optimal design for gene–environment interaction research. This approach would discover susceptibility variants, and then validate the findings in an independent sample of children. Designs that combine the strengths and methodologies of each field will yield data that can account for both genetic variability and the role of critical developmental windows in the etiology of childhood disease and development.

Childhood obesity and the built environment

Galvez, Maida P; Pearl, Meghan; Yen, Irene H. Current Opinion in Pediatrics. 22(2):202-207, April 2010. doi: 10.1097/MOP.0b013e328336eb6f

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March 21, 2010

Epigenetics and environmental health: The emerging science

The more we learn, the more we realize how much we don’t know.  A committee of the National Academy of Sciences held a workshop on July 30–31, 2009, to further understanding of the implications of epigenetic effects on public health and of the research that would be most important for efforts to inform public health leaders about epigenetic effects of chemicals.

What are the human health outcomes when genes (such as a tumor-suppressor gene) are turned on or off at different stages in life and in various tissues? Scientific evidence on animals and humans suggests that epigenetic changes are important and may be passed from one generation to the next.

The newsletter cited below gets a little technical, but provides an excellent overview of issues surrounding epigenetics.  I’ve summarized some of it.  (Most of this is over my head, but I think it’s evidence that we don’t have a full understanding of how the human body works and even less of an idea about how all sorts of environmental factors can affect it.)

Highlights of the meeting

  • What epigenetics is and how it works
  • Differences between genetics and epigenetics during animal development
  • DNA methylation, histone modifications, and transgenerational potential of effects

Possible Causes and Outcomes of Epigenetic Changes

Participants discussed how environmental chemicals, estrogenic compounds, and even social factors, such as child abuse and maternal care, may cause epigenetic changes.

Compounds such as nickel can induce hypermethylation and lead to altered gene expression patterns that can be inherited and lead to a growth or survival advantage for and lead to a growth or survival advantage for cancer cells.

In the late 1990s scientists showed that there was an association between dietary changes and changes in DNA methylation in mice.

Maternal behavior of rats affected DNA methylation of the glucocorticoid receptor gene in the hippocampus of the rat offspring.

One scientist reported that the effects of childhood social adversity on overall methylation patterns were more pronounced than the effects of having a mother who smoked.

Epigenetic changes related to cancer and asthma are being studied.

Possible tools and approaches, such as assay technologies,  for identifying environmental epigenetic stressors.

The following were among the topics discussed: biomarkers of disease susceptibility, animal models for studying epigenetics, screening tools, low-dose responses, interplay between genetics and epigenetics, epigenetic changes as exposure markers

Summary of the meeting by the moderator (p.3)

A half-page table which briefly describes discussion about our understanding of the epigenome and how we might be able to test for epigenetic changes.

Emerging Science for Environmental Health Decisions Newsletter: Use of Emerging Science and Technologies to Explore Epigenetic Mechanisms Underlying the Developmental Basis for Disease (PDF)

Workshop Webcast: Presentations on Emerging Science and Environmental Health

Presentations are available in mp3 (or mp4) and wmv formats.  Some include a PDF version.

Meeting sponsored by the Standing Committee on Use of Emerging Science for Environmental Health Decisions of the National Academy of Sciences Board on Environmental Studies and Toxicology

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