This post is by Leanne Chukoskie, Ph.D. Dr. Chukoskie is the Asst. Director Science Communication and Special Projects at Autism Speaks and Asst. Project Scientist, Institute for Neural Computation, UCSD.
Having not previously interacted with the National Institutes of Environmental Health Sciences (NIEHS), I didn’t know what to expect. I must admit a tendency to equate the National Institutes of Health with the pinnacle of ivory tower research and a somewhat “stuffy” perspective on science. I could not have been more off base in describing the inaugural meeting of the Partners in Environmental Public Health (PEPH).
The initiative aims to bring together academia and community stakeholders as partners in improving environmental health, and this was clearly a charge that the leadership and participants took seriously (read a description of the meeting). The passion of the people participating in this meeting was palpable. Many of the community organizers and research partners in attendance have been seeking solutions for local environmental problems for years. Spontaneous applause and whoops from the audience erupted in response to community-empowering comments or discussion. This wasn’t your typical scientific conference! After each discussion session, the moderators had to actively intervene to end the questions and suggest that the conversation continue over the next break, lest we get horribly off our time schedule.
At the meeting my colleague, Alycia Halladay, and I conversed with other public health advocates about what we and other organizations are doing to disseminate research findings to members of the community. How were we learning what issues concern the community most? How do we use that information to address those concerns? How are we delivering scientific information about autism to the public and are they “getting it”? These other groups wanted to learn from us, and we from them.
We learned about an exceptional program that trained portreros (trusted communicators in the local Hispanic community) in various aspects of environmental science understanding using hands-on science demonstrations. The portreros then met with other members of their community to convey needed information about local environmental risks surrounding a superfund clean-up site. Could we develop the resources to train our team of volunteer Science Ambassadors at Autism Speaks similarly?
We also heard an important presentation from Michael Yudell, Ph.D., M.P.H. of Drexel University who spoke about communicating autism research findings to the public in a clear, direct and useful manner. Citing the history of how “blame” has been used by different ways and different groups to identify the causes of autism, Dr. Yudell offered recommendations for improving the dissemination of research based on a meeting organized at Drexel last year
It is in meetings like this is where the rubber meets the road. There are so many areas of opportunity for autism, which is one of NIEHS’ priority areas of investigation, including opportunities for organizations and other community advocates to partner with academia and apply for grants. Most importantly, however, this initiative enjoys ongoing support from the government.. We look forward to making the most of the opportunities offered and working with you, the autism community, to make the changes we need most.
Recent reports have speculated on the role of Vitamin D in autism spectrum disorders (ASD). While no direct link to autism has been established, Vitamin D is an important dietary component and there is widespread concern about the increase in Vitamin D insufficiency and deficiency across the world. The term “insufficiency” is used when there is biological evidence of a deficiency of Vitamin D in the absence of any clinical signs.
Autism Speaks is currently supporting research to better identify and characterize the role of Vitamin D, the genes which are activated by Vitamin D, and how environmental factors may mediate autism symptoms. Last year, the National Health and Nutrition Examination Survey released data collected from 2001 to 2004 showing that the prevalence of Vitamin D insufficiency is on the rise from previous years. Coincidentally, the Vitamin D council issued a report which hypothesized that these lower levels of Vitamin D may be associated with the increase in autism seen in the last decade.
In order to study this further, in 2010, two separate research groups in Sweden have studied the relationship between maternal and child Vitamin D levels in families affected with autism. Results showed that children with autism and their mothers both showed the lower Vitamin D levels compared to families with children with other conditions, such as depression. The group differences in Vitamin D levels was not statistically significant, however. The authors suggest that lower Vitamin D levels may be a predisposing factor in autism, not a specific cause.
These studies did not attempt to examine genetic variants associated with the Vitamin D hormone receptor (VDR). This receptor is activated by the active forms of Vitamin D, and signals target genes to turn on or off. Through its Environmental Factors Initiative, Autism Speaks is currently supporting a project at the University of California at Davis, led by Bruce Hammock, Ph.D. to investigate variants in the VDR and their relationship to immune problems in children enrolled in the on-going Childhood Autism Risks from Genetics and the Environment (CHARGE) study. This study will provide a more complete picture of the source of Vitamin D insufficiency, the biological consequences, and the contributions to autism and co-morbid symptoms. The goal is to possibly identify a group of children who would benefit from additional Vitamin D supplement therapy.
What does this mean for autism?
Studies examining the diet of children with autism suggest that some children on the spectrum may not be receiving proper nutritional values of foods rich in Vitamin E and D, as well as fiber and iron. The American Academy of Pediatrics released new guidelines in 2008 to prevent Vitamin D deficiency symptoms in all children, including use of at least 400 IU Vitamin D supplements to ensure serum levels of 25-hydroxyvitamin D (the form detected in blood) are at least 50 nmol/L. Because previous studies have not demonstrated a direct link between low Vitamin D and autism, families should talk to their doctors before beginning a therapy regimen that differs from current guidelines on dietary and sun exposure. Additional research in this area examining Vitamin D, as well as sources of Vitamin D, will identify possible gene x environment interactions in the role of this prohormone in ASD.
Learn more about the latest basic, clinical and treatments grants that Autism Speaks is funding.
This post is by guest blogger Dr. Philip Landrigan. Philip J. Landrigan, M.D., M.Sc., the Ethel Wise Professor and Chair of the Department of Preventive Medicine, is a pediatrician, epidemiologist, and internationally recognized leader in public health and preventive medicine. He has been a member of the faculty of Mount Sinai School of Medicine since 1985, the Chair of the Department of Preventive Medicine since 1990 and is also the Director of the Children’s Environmental Health Center. Dr. Landrigan has been a leader in developing the National Children’s Study, the largest study of children’s health and the environment ever launched in the United States.
The causation of autism is the subject of intense inquiry. Genetic factors are clearly important, and elegant genetic research has identified a series of anomalies – gene mutations, gene deletions, and copy number variants (CNVs) – that are persuasively linked to autism. But none accounts for more than a relatively small fraction of cases. Moreover there is substantial imbalance between the extensive and highly sophisticated information on the genetics of autism and the scarcity of investigation into potential environmental causes. This situation raises the possibility that still undiscovered environmental exposures also contribute to causation of autism perhaps acting in synergy with inherited genetic vulnerabilities.
The article I recently published in Current Opinion in Pediatrics explores the possible contribution of early environmental exposures in the causation of autism, with particular focus on the possible role of toxic chemicals. Support for the possibility of an environmental contribution to autism comes from the following two sources:
(1) Current understanding of the exquisite vulnerability of the developing human brain to toxic exposures in the environment; and
(2) Proof-of-concept studies that specifically link autism to environmental exposures experienced prenatally. These include thalidomide, misoprostol, valproic acid, maternal rubella infection, and most recently the organophosphate insecticide – chlorpyrifos, which is linked in prospective epidemiologic studies to Pervasive Developmental Disorder, a form of autism. The time of greatest vulnerability to these exposures appear to be the first trimester of pregnancy.
There is no credible evidence that vaccines cause autism. To address the possibility of a connection between the MMR vaccine or thimerosal and autism, a dozen highly credible studies have been undertaken in the US, the UK, Europe, and Japan. None have found credible evidence for a connection between the MMR vaccine or thimerosal and autism. Most persuasive among these studies is an investigation in Yokohama, Japan. There, the MMR vaccination rate declined significantly between 1988 and 1992, and no MMR vaccine was administered in 1993 or thereafter. Despite declining immunizations, the cumulative incidence of ASD increased significantly each year from 1988 through 1996 and rose especially dramatically beginning in 1993. Overall incidence of autism nearly doubled in those years.
To reveal as yet undiscovered environmental causes of autism, an interdisciplinary autism discovery strategy is proposed that combines toxicological screening, neurobiological research and prospective epidemiological study. Although the MMR vaccine and thimerosal are not credible causes of autism, the possibility remains open that there exist unrecognized environmental causes of autism. Most likely these are to be found among the High Production Volume chemicals to which pregnant women and children today are routinely exposed. The rationale for seeking environmental causes of autism is that, once discovered, these causes are potentially preventable.
A successful strategy for discovering the environmental causes of autism will need to be highly interdisciplinary. It will need to bring together researchers from toxicology, epidemiology, developmental psychology, developmental neurobiology, neuropathology, molecular genetics, genomics, proteomics, functional neuroimaging and medical informatics. Key elements will include toxicological testing of chemicals to which pregnant women are at risk of exposure, basic neurobiological research and prospective epidemiologic study.
Large-scale, prospective epidemiological studies such as the recently launched US National Children’s Study are extraordinarily powerful engines for discovery of the environmental causes of autism. The National Children’s Study is the largest study of children’s health ever undertaken in the US. It will follow 100,000 children—a statistically representative sample of all children born in the United States from conception to age 21. It is the first large-scale prospective study of children’s health to specifically measure children’s environmental exposures, prenatally as well as after birth, using a combination of maternal and infant biological markers and direct sampling of the ambient environment. It will collect samples for genetic analysis from each mother and child. The National Children’s Study will attempt to link children’s prenatal and postnatal environmental exposures with the subsequent appearance of disease and dysfunction.
Given the currently reported prevalence of autism in the US, the study can be expected to include nearly 700 children with autism. The National Children’s Study will provide an unparalleled opportunity to examine interactions between genetic and environmental factors in the genesis of autism. It will also bring together the researchers needed to succeed in understanding the causes of a complex disorder like autism. Potential for breakthrough discovery is high.
Landrigan, P (2010) What causes autism? Exploring the environmental contribution. Current Opinion in Pediatrics 22.
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our eighth item, Creation of Neuroligin-3 Mutant Mouse, is from Autism Speaks’ Top 10 Autism Research Events of 2007.
Animal models have long been employed to replicate some of the behavioral and biochemical characteristics of autism. The models are chosen for study either because they have behaviors reminiscent of autism, or because they have received genetic or environmental manipulations believed to be linked, directly or indirectly, to autism.
Yet, only with the recent progress of detailed genetic studies in developmental disorders have these models been based on the actual genetic differences found in humans with autism. Some of these newer models for autism include mouse models of medical genetic syndromes that show overlap with autism, e.g., Fragile X syndrome, Rett syndrome and Tuberous Sclerosis. However, no model existed that contained the precise genetic defect found in anyone whose autism is not caused by one of these other genetic syndromes. This changed in October 2007, when researchers in Texas reported they had succeeded in replacing the mouse neuroligin-3 gene with a human version containing the exact mutation discovered in 2004 to be the cause of autism in a Swedish family with two affected brothers. Excitingly, the initial exploratory studies have found the “humanized neuroligin-3″ mouse has several unusual behaviors, including deficits in some social behaviors and an increased ability for spatial learning in a swimming test.
This mouse provided the research community with a strong new tool to directly assess the neurobiology, behavioral deficits and, conceivably soon enough, treatment approaches for autism. Such models are a vital part of the drug discovery process because measurement of changes in their behaviors can be used as surrogate markers for preclinical evaluation of new therapeutics.
Since this story was first run: Genetic studies continue to provide new opportunities for the generation of animal models of autism, including many related to the function of the neuroligins. In 2009 the same group of researchers carried out a behavioral characterization of mice lacking the neurexin-1alpha gene, which creates proteins that serve as binding partners for the neuroligins. Published in the Proceedings of the National Academies of Science, the scientists have now discovered that the neurexin-1alpha mice have abnormal brain physiology and increased repetitive behaviors.