The Mount Sinai Children’s Environmental Health Center, in partnership with Autism Speaks, is holding a one day workshop, Exploring the Environmental Causes of Autism and Learning Disabilities, at the New York Academy of Medicine on Wednesday, December 8, 2010. The goal of the workshop will be to develop new strategies for discovery of environmental risk factors for autism, autism spectrum disorder (ASD) and other neurodevelopmental disorders in children.
The workshop will help identify opportunities to study gene/environment interactions in autism, and help guide research priorities for the newly formed Autism and Learning Disabilities Discovery and Prevention Program at Mount Sinai. Scientists from National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention, National Institute of Child Health and Human Development and leading academic institutions from around the world will present recent research and engage in discussions to identify gaps and opportunities, especially in the area of environmental causation by toxic chemicals.
Staff bloggers Alycia Halladay, Ph.D., Director of Environmental Sciences and Leanne Chukoskie, Ph.D., Assistant Director of Science Communication and Special Projects
A study published on Monday in Pediatrics revealed that newborns who experienced jaundice were at greater risk for a later diagnosis of autism spectrum disorders. Jaundice is a common condition where bilirubin is not properly excreted by the liver, builds up in the blood and leads to a slight yellow pigment of the skin. Bilirubin is a neurotoxin and it is well established that untreated severe jaundice can lead to brain damage and even death. Fortunately, despite the fact that jaundice is very common in newborns, it usually resolves with minimal or no intervention within a few days of birth.
Previous studies have investigated the potential for increased risk of ASD following jaundice with mixed conclusions. The advantage of this study is that the researchers used a large health registry database in Denmark including over 700,000 birth and associated developmental health records. The researchers looked at the development of 35,766 children diagnosed with perinatal jaundice (4.9% of the entire study population). They looked for children diagnosed with ASD as well as a broader definition of disorders of psychological development, which included speech delay. The risk of an ASD was found to be about 52% greater in children who experienced jaundice as newborns versus those who did not.
This may be an overestimate because factors such as season of birth, gestational age, parental age, gender, and the birth order of the child were not considered in this comparison. When these factors were considered, the overall risk increase was no longer statistically reliable. However an interesting pattern emerged from individually considering the factors.
Although preterm children typically experience a greater risk of autism by virtue of the challenges of prematurity, it is the full term babies that have an increased risk for ASD after exposure to jaundice. The authors speculate that there may be some unique window of vulnerability in brain development around 40 weeks gestational age that can explain this finding.
Another interesting relationship emerged from looking at cases from mothers who had previously had children versus those giving birth for the first time. Jaundice increased the risk for developing an ASD in children who were second or later born, but conveyed no increased risk for first born children. This effect is also a bit of a scientific mystery, however we do know that second and later-born children can be exposed to maternal antibodies that accumulate from previous pregnancies.
Lastly, the authors found that birth during the winter months was statistically associated with greater ASD risk than birth in the summer months. Exposure to daylight helps to break down bilirubin, so it is possible that individuals born in summer months, though diagnosed with jaundice had lower levels of bilirubin in their blood simply because they were exposed to more sunlight. The authors also note that sunlight is required for Vitamin D synthesis and low light levels in the winter may alter the body’s ability to as synthesize Vitamin D. Vitamin D deficiency is another autism risk factor under investigation. Autism Speaks is currently supporting a study examining how Vitamin D levels at birth and genes for the Vitamin D receptor are related to a later autism diagnosis.
In summary, it is important to note that although this paper brings many new considerations, it does not establish that jaundice causes autism. Instead, this paper reports on the risk of developing ASD after exposure to jaundice. This risk is significantly modified by several factors. Data from this study suggests that babies with jaundice who were born prior to 37 weeks gestation have little to no increased risk of ASD. However, the data also indicate a substantially elevated risk for full-term babies born to mothers with previous pregnancies and also full-term babies that were born during winter months. Hopefully, this and other information about medical conditions at birth will lead to the further development of screening tools to identify individuals at risk for a later autism diagnosis. Before that is done, scientists need to determine the mechanism by which jaundice may be contributing to the risk of developing ASD. Further research will been needed to determine whether bilirubin is itself an environmental risk factor, or if jaundice is a consequence of both genetic and environmental effects that elevate the risk of developing autism.
On September 8, the National Institute for Environmental Health Sciences and Autism Speaks organized a brain-storming meeting in North Carolina entitled “Autism and the Environment: New Ideas for Advancing the Science”. Researchers, scientists, and parent advocates from within and outside the field of autism were invited to participate. Over the course of the day, the group’s objective was to share novel ideas and unique perspectives in identifying and overcoming the primary obstacles to progress in the field of environmental health research in autism. From these discussions the group was charged with identifying the best opportunities for accelerating research aimed at understanding the role the environment plays in the risk for autism. What made this meeting unique from others is that autism researchers with expertise in the unique challenges of discoveries in this disorder were invited together with experienced, senior researchers in other disorders with known genetic and environmental risk factors. This included schizophrenia, Parkinson’s Disease, and breast cancer. For example, Dr. Caroline Tanner described the sequence of scientific discoveries that led to the conclusion that Parkinson’s Disease has both environmental and genetic causes, and how researchers are using this information to better understand how the two interact. Dr. Tanner commented that, like autism, Parkinson’s Disease is associated with gastrointestinal problems, noting that such problems often occur before the onset of the motor problems that are characteristics of this disorder. Other scientists pointed out how both epidemiological evidence and basic science discoveries have suggested that early immune system challenges, such as maternal influenza, can influence fetal brain development, resulting in an increased risk for schizophrenia. Another feature of the discussion was the broad, inclusive nature of environmental factors under consideration, as well as how basic science and epidemiology can work together in parallel, rather than sequentially, to identify and validate suspected environmental targets.
The meeting was broadcast live via webcast and a summary report will be shared with the public and the NIH Interagency Autism Coordinating Committee for further consideration and comment. Ultimately this report will offer guidance in setting priorities in future environmental research in autism. Some of the suggestions included taking advantage of a variety of existing epidemiological studies the use of newer technologies for data collection of personal environmental exposures – such as sensors that can be worn on the body that are currently under development. Existing epidemiology studies that may not currently include autism as an outcome may be able to be built upon by adding autism as an outcome and gathering additional information on exposures of particular interest In addition, representatives from the National Toxicology Program presented approaches using bioinformatics and high throughput technologies to quickly screen for a variety of environmental exposures of interest. Because autism is complex, the assay may not be simple, and the group stressed the importance of basic research in science to help inform the process. This includes high quality, well designed research in cell biology, neuroanatomy, neurophysiology and genetics. Genetic research will continue to be essential to better understand how individuals with certain genotypes may be vulnerable to specific environmental exposure and to provide clues into the biological systems that are affected in autism. The new findings in genetics with regards to copy number variations are going to be essential to identify biological pathways that may be affected by specific environmental exposures.
As autism is a disorder with multiple symptoms and multiple etiologies, both big and small ideas, short and long term projects were identified for further consideration. Please check the Autism Speaks website for updates on this meeting and plans to follow up on the ideas presented. More information about the agenda and the participants can be found here. We will post a link to the full meeting once it is available.
Last week, the Senate Environment and Public Works Committee convened a panel of experts to investigate the role of environmental factors in autism spectrum disorders (ASD; link to web archive for video). Although genetic factors are known to contribute to the risk of autism, we also need to understand environmental factors and their interactions with genetic susceptibility.
The dramatic increase in autism prevalence over the last two decades—over 600% during this period—underscores the need for more research on environmental factors. Our understanding of typical brain development combined with what we’ve learned from examining the brains of individuals with autism have focused efforts on the prenatal and early postnatal environment. To investigate environmental factors that may be active during this time, researchers are casting a wide net on potential environmental agents that can alter neurodevelopment, including exposure to metals, pesticides, polybrominated diphenylethers and other chemicals.
Isaac Pessah, Ph.D., Director of the University of California, Davis, Children’s Center for Environmental Health and Disease Prevention, participated in the panel and said in his testimony, “We must identify which environmental exposures and combination of exposures are contributing to increased overall risk in the population and identify the most susceptible groups. Only by bringing together the concerted effort of multidisciplinary teams of scientists can we identify which of the >80,000 commercially important chemicals currently in production promote developmental neurotoxicity consistent with the immunological and neurological impairments identified in individuals with idiopathic autism”.
To help speed an understanding of environmental factors, Autism Speaks is supporting research on several fronts. In 2008, Autism Speaks launched the Environmental Factors Initiative to fund investigators researching aspects of environmental causes and autism.
A collaboration with the National Institute for Environmental Health Sciences (NIEHS) has resulted in a network of 35 international scientists who gathered at this year’s International Meeting for Autism Research (IMFAR) to promote collaboration, identify gaps in our understanding and foster opportunities for innovative research which is discussed in more detail in Dr. Dawson’s 2010 IMFAR recap. This fall, Autism Speaks and NIEHS will co-sponsor a workshop to help identify the most promising strategies and scientific directions for understanding the role of the environment in ASD.
A large collaborative study which will pull together data from six international registries is being funded by Autism Speaks to explore early environmental risk factors for ASD.
Autism Speaks is also leveraging longstanding investments to make the best use of research resources that currently exist. For example, the Autism Genetic Resource Exchange (AGRE), a premiere genetic resource for scientists studying autism, is now collecting environmental data from families to pair with the genetic and medical data. Autism Speaks has partnered with the National Institutes of Health to fund the the EARLI and IBIS research networks to study environmental factors in infants at risk for autism. The EARLI network is following 1200 mothers of children with autism from the start of another pregnancy through the baby sibling’s third birthday. The IBIS network is charting the course of brain development in infant siblings of children with autism. Together with Autism Speaks, these groups are exploring both genetic and environmental risk factors for ASD.
Taken together, Autism Speaks’ investment in research on environmental factors promises to shed light on an important area of autism research that has until recently remained in the shadows. We look forwarding to following the new directions illuminated by the discoveries made possible by these various research opportunities.
This guest post is by Andrew Mencinsky, Executive Director of Surfers’ Environmental Alliance.
Each year as I organize and advocate for our SEA Paddle NYC event, I am always asked, “why autism?” From the event’s inception, Surfers’ Environmental Alliance has endeavored to promote coastal preservation and the therapeutic effects surfing has on autistic and special-needs children. It has become quite apparent to SEA that without the protection of our surf breaks and waterways, pollution and industry will continue to negatively impact people’s health and well being, and forever change our marine environment.
Surfing is contingent upon protected shorelines and unpolluted waterways. From this basic principal, the Surfers’ Environmental Alliance mission was born. It may be obvious to most, but I can never state enough that clean water is inherent to the sport of surfing. Unlike relocating a stadium or practicing at a new baseball field, surfers do not have the luxury of creating a new ocean. Once a surf break is eliminated, or polluted water impacts a surfer’s health, the consequences become dire.
To an avid surfer and coastal resident, the importance of advocacy groups like SEA was apparent to me. It wasn’t until I saw the work of Surfers Healing, a SEA Paddle beneficiary, that it all came together for me on a much grander scale. The work of Surfers Healing made me realize surfing is much bigger than the industry and the individuals it encompasses; it can bring immeasurable joy to people’s lives. In this case, I witnessed surfing bringing smiles to parents and children who face the sometimes devastating challenges of autism and other mental conditions; I had the privilege of witnessing what many families were calling “the best day of their life.”
After my exposure to Surfers Healing, another variable was added to SEA’s mission: autism and environmental triggers. My home state, New Jersey, currently has the highest rate of autism in the nation. It is my strong belief that there is something in our environment that is contributing to this ever-increasing condition. For all these reasons, I could think of no better alliance for SEA Paddle NYC than with surfing and autism advocates. The link between the two – ENVIRONMENT – is an issue that is important now more than ever.
This passion and alliance between what seem like two incredibly different worlds was created with the help of Darrick Doerner, co-founder of SEA Paddle NYC. Six years ago, Darrick and I took a jet-ski ride from the Jersey Shore to lower Manhattan; our trip inspired the SEA Paddle concept. The first year was definitely a challenge, but we rallied 40 paddle boarders to take the 28-mile journey around New York City in support of four beneficiaries, one being Autism Speaks. Over the past four years, SEA Paddle NYC has grown in scope thanks to a dedicated group of stand-up paddle boarders, pro athletes, actors, musicians, and environmental advocates. Each year, we garner more support and raise more funds for organizations that are bringing support to special-needs families around the country.
We are very excited to return to Manhattan on August 13 for our fourth-annual SEA Paddle NYC. An estimated 200 participants will converge on New York’s waterways to raise awareness and monetary support for this year’s eight wonderful beneficiaries. We have an impressive fundraising goal of $300,000. With the incredible response we have received so far, I know we will meet this target. This year will also be the first time SEA hosts its popular after-party celebrations in New York immediately following the paddle. The fun will start on the afternoon of the 13th at Water Taxi Beach with our Ultimate Beach Party. We’ll then celebrate in style at our White Water Evening fundraising dinner on the third-floor viewing decks of the South Street Seaport catered by Harbour Lights Restaurant. We have a few spots open in our charity poker tournament, so please join us for a memorable evening at the Seaport!
As usual, SEA has to thank Autism Speaks for their support of our event. Everyone at SEA is looking forward to standing-up to autism on August 13!
Genetic research is one of the exciting avenues of investigation that was highlighted at this year’s IMFAR meeting. The section on human genetics started with a description of the largest study of autism twins to date. This study, described by Dr. Joachim Hallmayer, has concluded the data collection phase and is beginning to shed new light on how much autism can be explained by genes and how much by environment. Because identical twins share 100% of their DNA while fraternal twins share only approximately 50%, geneticists can compare the relative contribution of genes and environment, since it is assumed that for each twin pair, the environment is the same. Clearly, both environment and genes are involved but this study may help to identify to what extent.
Dr. David Ledbetter described his effort to gather anonymous genetic information on chromosomal microarays from hundreds of thousands of patients with autism spectrum disorder and developmental delay. He is doing this by forming partnerships with over 120 clinical labs throughout the U.S. Dr. Ledbetter, a world-reknown expert in cytogenetics, has the knowledge and respect of the scientific community to achieve the goal of creating data standards and pooling information to show which chromosomal changes are most often identified in these groups. Deletions in regions on chromosomes 16 and 22 are identified consistently. Although still rare, an understanding of altered genes in these regions may lead us to identify new subtypes of autism.
Other talks focused on studies of brain and face development (since these happen at the same time) in families with autism from the Autism Genetic Resource Exchange, an update from the Autism Genome Project, and a fascinating talk from Sun-Chiao Chang (working with Dr. Susan Santangelo) on sex-specific effects in autism spectrum disorder. Ms. Chang identified several genes which seem to have an effect only in males, possibly helping to explain the common finding that there are four times as many males with autism as there females.
To read complete coverage from IMFAR, please visit http://www.autismspeaks.org/science/science_news/imfar_2010.php.