Pregnant mothers join search for causes of autism
Pregnant women and new moms who already have one child with autism joined researchers and federal officials on Aug. 8 to announced UC Davis' latest initiative in autism science. Known as MARBLES, for Markers of Autism Risk in Babies-Learning Early Signs, it is the first prospective study that begins the search for causes and early markers of the disorder during pregnancy. Funding for the new study will be part of a $7.5 million commitment to UC Davis autism research from the U.S. Environmental Protection Agency U.S. EPA) and the National Institute of Environmental Health Sciences NIEHS).
Inspiration for launching MARBLES
The inspiration for launching MARBLES came from Irva Hertz-Picciotto, an environmental epidemiologist and principal investigator of the CHARGE (Childhood Autism Risks from Genetics and the Environment) study. CHARGE looks at the influence of environmental factors, the role of genetics and the interplay between the two in the development of autism, a pervasive developmental disorder marked by poor verbal and communication skills, repetitive behaviors and an inability to form social connections.
“As comprehensive as CHARGE is, I realized the limitations of any study that begins looking for causes of autism after the diagnosis is made at age 2 or 3. In that study design, researchers are forced to extrapolate backwards in time to determine what caused the disorder to occur,” said Hertz-Picciotto, who is also a M.I.N.D. Institute investigator. “The advantage of MARBLES is that we aren't starting after autism develops in order to study it. We are instead following events as they happen in real time to help us determine how and why it occurs.”
— Irva Hertz-Picciotto, UC Davis environmental epidemiologist
Requirements to be a MARBLES participant
MARBLES participants are required to have at least one child with autism, since such women are at least 10 times more likely to have another child with the disorder. They undergo a series of intensive evaluations during pregnancy, birth and nursing of their environmental exposures, genetics and immune systems. After a mother gives birth, her new child's development is carefully monitored until age 3. According to Hollie Fletcher, MARBLES participant and mother of 4-year-old Jacob, who has autism, the expected commitment for those involved is significant, but the outcomes will be worth it.
“I really like the fact that my newborn will be monitored by specialists for three years so we can know as soon as possible if she has any developmental issues. The sooner we know about the possibility that something might be wrong, the sooner we can begin getting interventions to help,” she said. “I also want to contribute to what we'll learn from the study. If I can help others so they don't have to go through what we went through in terms of getting answers and help for our son, I want to be a part of it.”
Hertz-Picciotto believes a key outcome of MARBLES will be expanding initial results of CHARGE data indicating that the immune systems of children with autism function quite differently than the immune systems of typically developing children, since it's possible those immune system dysfunctions began in the earliest phases of life.
“What we see in children with autism could be due to an inflammatory response on the part of their mothers' immune systems during pregnancy, perhaps due to a virus or some other external influence,” she said. “MARBLES assessments will help us find out when immune system development actually begins to go off course.”
Center for Children's Environmental Health
The $7.5 million in federal funding over the next five years will go to the UC Davis Center for Children's Environmental Health (CCEH) which, in turn, will fund CHARGE, MARBLES and other research aimed to discover how environmental toxicants can affect child development. Led by molecular biologist and M.I.N.D. Institute investigator Isaac Pessah, CCEH began in 2001 with similar funding levels from the U.S. EPA and NIEHS. At the time, Pessah was determined to find out if autism was more than a brain and behavioral disorder and uncover the intricate cell-environmental connections that could lead to its onset.
— Isaac Pessah, molecular biologist
“Autism is very complex. It is probably several disorders converging in a common diagnosis. We actually don't anticipate finding just one factor that causes it but will instead uncover patterns of susceptibilities and external influences that can lead to different forms of the disorder,” said Pessah, whose own research points to immune system dysfunction in autism as a focus for finding answers to what causes the disorder. “We have discovered that the universe of suspect toxins includes those that directly interact with neuronal tissue as well as with critical immunologically active cells, giving us important targets for our next research efforts.”
Pessah founded CCEH to ensure that results from biological studies influenced the design of epidemiological studies, and vice versa. This multidisciplinary philosophy has already yielded significant outcomes from 2002-2007. The center's teams of neuroscientists, molecular biologists, immunologists, pediatricians, geneticists and epidemiologists have discovered:
- An increase in plasma levels of the hormone/cytokine leptin in children with early onset versus regressive autism, identifying the first biological distinction between the two forms of the disorder.
- Abnormalities to the auditory cortex of rat pups whose mothers were exposed to a specific class of PCBs during pregnancy and early weeks of nursing. In children with developmental disorders, including autism, the auditory cortex responds abnormally to sound, leading some scientists to believe this is a basis of the disorder.
- The first evidence that dendritic cells obtained from mice show unprecedented sensitivity to the mercury-containing preservative thimerosal, resulting in fundamental changes in the immune system's ability to respond to external factors. As a result, CHARGE assessments will be expanded to determine if the same immune system dysfunctions are apparent in the blood of children with autism.
- Mice lacking both copies of the Homer1 gene show decreased aggression and increased social behavior, while mice lacking one copy show increased aggression. The findings demonstrate that genetic manipulations can alter social interactions in mice and provide new insights into the neurobiology of atypical social behavior.
“This Children's Environmental Health Center at UC Davis will be an essential component of EPA's work to understand and reduce the risks of our most challenging environmental childhood illnesses,” said George Gray, EPA assistant administrator for research and development. “Learning if and how the environment interacts with genetic factors during early development will provide the scientific knowledge necessary to reduce the risks of childhood diseases and create healthier environments for all of us.”
“The NIEHS is fully committed to supporting research efforts into children's health. Studies like these will help advance our understanding about the underlying causes of autism,” said David A. Schwartz, a physician and director of the NIEHS. “The MARBLES study exemplifies our commitment to support research that will help families suffering with the consequences of this devastating disorder.”
“We are very grateful for the continued support of the federal government in helping us continue and expand this important work,” said Pessah. “We have come a long way in a very short period of time thanks to their initial funding. We are confident that our continued biological studies combined with assessments of CHARGE and MARBLES data over the next five years will lead to even more breakthroughs that reduce autism's complexities.”
How to particpate
There are 28 women currently enrolled in the initial phases of MARBLES, 15 of whom have given birth. With long-term funding now secure, the goal is to quickly increase participation to 200 women who are pregnant or considering getting pregnant and who already have at least one child with autism. Women interested in enrolling who live within a two-hour driving distance of Sacramento can call (530) 754-0612 or toll-free (866) 550-5027 or e-mail firstname.lastname@example.org for more information and to find out if they meet recruitment criteria.
For more information about the UC Davis CCEH, visit www.vetmed.ucdavis.edu/cceh. To learn more about the U.S. EPA and NIEHS Centers for Children's Environmental Health and Disease Prevention research programs, visit www.epa.gov/cehc and www.niehs.nih.gov/translat/children/children.htm.