Center for Children's Environmental Health

PRESS RELEASE - AUGUST 8, 2007

PREGNANT MOTHERS JOIN SEARCH FOR CAUSES OF AUTISM

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U.S. EPA and NIEHS provide $7.5 million for UC Davis studies on environmental triggers and biological markers - Pregnant women and new moms who already have one child with autism joined researchers and federal officials today to announce 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). 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. 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. 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. 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 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. 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. There are 20 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 marbles@ucdavis.edu for more information and to find out if they meet recruitment criteria. 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.

PRESS RELEASE - MONDAY, APRIL 23, 2007

CLASS OF PCBs CAUSES DEVELOPMENTAL ABNORMALITIES IN RAT PUPS

Corinna Kaarlela, News Director

Source: Jennifer O’Brien (415) 476-2557

E-mail: jobrien@pubaff.ucsf.edu

Web: www.ucsf.edu

TO COINCIDE WITH PUBLICATION IN PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

Scientists have determined that a specific class of PCB causes significant developmental abnormalities in rat pups whose mothers were exposed to the toxicant in their food during pregnancy and during the early weeks when the pups were nursing.

This class of PCB traditionally has not been considered particularly hazardous.

The pups were estimated to have levels of the toxicant in their blood that were roughly equivalent to those found in the blood of breast fed babies of mothers exposed to extremely high levels of the toxicant from contaminated fish, soil, water and air in high-risk environments.

The study, reported in the on line, Early Edition of Proceedings of the National Academy of Sciences the week of April 23-27, showed that the toxicant altered the rat pups’ auditory cortex, the part of the brain that processes sound. The neural circuitry of this region was disorganized and the nerve cells had a decreased capacity to change, or “learn,” in response to sound. The capacity of the brain’s cortex to change in response to stimuli contributes to the progressive development of cognitive function.

In children with a variety of developmental disorders, including language impairments and autism, the auditory cortex responds abnormally to sound. Some scientists believe this is the basis of the conditions.

While the scientists emphasized that their finding did not demonstrate that the toxicant causes developmental disorders, they said that, given its severe impact in the rat pups and the prevalence of this class of PCB in the environment – known as non-coplanar PCBs -- and related chemicals warrant serious attention.

“The study indicates that there are chemicals out there, this being just one example, that could profoundly affect development,” says Tal Kenet, PhD, who led the research while a postdoctoral fellow in the lab of senior author Michael Merzenich, PhD, UCSF Francis A. Sooy Professor of Otolaryngology and a member of the Keck Center for Integrative Neuroscience at University of California, San Francisco.

“This is a red flag,” says Merzenich. “The impact of this class of chemicals, whose toxicity has been under-appreciated, must be studied in human populations, and fast.”

The finding builds on recent cell culture studies by co-author Isaac Pessah, PhD, professor of molecular biosciences at University of California, Davis, showing that non-coplanar PCBs significantly influence chemical and electrical signaling between neurons that affects brain development and learning.

While developmental disorders have a strong genetic component, many scientists, including the authors, believe that, in some circumstances the disorders are only expressed when environmental factors act upon inherited mutated genes.

“We know that some environmental risk applies in the early developmental history of the brain in the fetus and baby,” says Merzenich, a pioneer of studies on the neural basis of learning and memory and the neural origin of developmental disorders.

“People have struggled with what kinds of factors these might be. I think environmental poisons, including the chemical we’ve examined in this study, are very good candidates.”

Given that the rat pups in the study did not have a genetic susceptibility to a developmental disorder, the scientists suspect that the vulnerability might be greater in genetically susceptible human populations.

The study did not attempt to distinguish whether the PCB affected the rat pups’ developing brains while they were gestating or while they were nursing, but scientists reported in 2003 that infants who were breast fed for more than three months had 6.6 times higher levels of PCBs in their blood plasma than infants who did not breast feed.

This finding, coupled with other factors -- particularly an increase in the rate and duration of breast feeding in the United States, epidemiologic evidence of negative effects on cognitive function in children, and lab evidence in rats, following PCB exposure in high-risk environments – is noteworthy, says Kenet, who is now a junior faculty member at Harvard Medical School and Massachusetts General Hospital.

“Breast feeding is by far the optimal choice for the vast majority of infants, given its indisputable nutritional and immunological benefits," says Kenet, "and our findings, conducted in rats, by no means suggest women should alter their nursing practice. The finding does suggest the need for studies in human populations to determine whether there are possible risks associated with breast feeding in cases of extreme exposure to this class of chemicals, in particular in infants who may have a genetic predisposition to developmental disorders based on their family history.”

Polychlorinated biphenyls (PCBs), used mostly as coolants and lubricants beginning in the 1930s, were banned in 1977. Early toxicology studies focused mostly on a subset of PCBs known as coplanar PCBs, which were shown in cell culture and animal models to pose a serious health risk. Recent studies, however, have shown that non-coplanar PCBs are particularly stable, are less susceptible to degradation by organisms in the environment, and predominate in environmental and human tissue samples over their counterparts.

In the current study, the scientists focused on a non-coplanar PCB known as PCB95, which is exemplary of a type of PCB prevalent in the environment, and has qualities that could make it among the more hazardous.

In the primary experiment, one set of adult rats was exposed to the toxicant in their food during pregnancy and during the first three weeks after giving birth, when they nursed their pups. Another group was fed normally. After both sets of pups had been weaned, the researchers recorded the electrical activity of neurons in their primary auditory cortex, the first sensory region to develop in the cortex.

The results were dramatic, says Kenet. While the brain region of the pups raised without exposure to the toxicant was developing typically, the brain region in the pups exposed to the toxicant in utero and while nursing was profoundly altered.

“The animals could hear, but their brain’s representation of what they heard was grossly disturbed,” says Merzenich.

In one pronounced change, the balance of inhibitory and excitatory signaling between nerve cells, which contributes to the appropriately controlled responses of the brain to stimuli, was disrupted. Strong evidence indicates that there is imbalance in signaling throughout the brain of children with some developmental disorders, such as autism, says Merzenich.

In a secondary experiment, the toxicant-exposed pups were raised in a modified sound environment in which they were exposed to continuous tone or noise pulses. It was here that the auditory cortex’s decreased capacity to change in response to sound was revealed. “This activity is crucial in the developing brain,” says Merzenich. “Interruptions in these early-learning progressions contribute to learning-related challenges.”

As the auditory cortex is the first sensory region to develop, its abnormal development in the rat pups could be just a hint of more pervasive effects of exposure, the scientists say.

PCB95 is closely related in its chemical structure to polybrominated diphenyl ether (PBDE), which is difficult to study and has only begun to receive attention for its environmental effects, says Kenet. It has been used in large quantities in the last 25 years, mostly in fire retardation in home and office furniture and electronics.

“We’ve done as yet unpublished studies with PDBEs,” says Pessah, director of the UC Davis Center for Children's Environmental Health. “The current finding could be just the tip of the iceberg.”

Other co-authors of the study were Robert Froemke, PhD, and Christoph Schreiner, MD, PhD, both of the Keck Center for Integrative Neuroscience at UCSF.

The study was funded by Cure Autism Now, the UC Davis M.I.N.D. Institute, the Jane Coffin Childs Foundation for Medical Research, the Sandler Program in Basic Sciences, the National Institutes of Health and the Environmental Protection Agency.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

For more information:

Kenet: http://www.nmr.mgh.harvard.edu/martinos/people/showPerson.php?people_id=667

Merzenich laboratory: http://www.ucsf.edu/neurosc/faculty/neuro_merzenich.html

UCSF Magazine, Dec. 2004, “Grasping Autism http://pub.ucsf.edu/magazine/200412/autism.html

UCSF Magazine, 2003, “Faculty Entrepreneur” http://pub.ucsf.edu/magazine/200305/learningcurve.html

Isaac Pessah:

http://www.ucdmc.ucdavis.edu/mindinstitute/ourteam/faculty_staff/pessah.html

http://www.ucdmc.ucdavis.edu/mindinstitute/

http://www.vetmed.ucdavis.edu/cceh

FOR IMMEDIATE RELEASE CONTACT: Marguerite Colston

DECEMBER 21, 2006 Phone: (240) 672-4734

Email: mcolston@autism-society.org

ASA Releases Research on Environmental Health and Autism
Autism Advocate Special Edition and website out today explore the role of neurotoxins on the prevalence of autism spectrum disorders

Bethesda, MD (12/21/2006) -- The Autism Society of America (ASA) today released a special edition of its magazine, Autism Advocate, which explores the critical effect of environmental toxins on the incidence and treatment of individuals with autism. Paired with a new ASA environmental health website highlighting leading scientists, professionals, and individuals affected by autism, this two-platform media launch is the first-ever effort to bring leading scientists, doctors, therapists, families and individuals with autism together to examine the linkages between environmental health and autism.

Autism Advocate: Environmental Health Issue By highlighting the role of environmental factors which may possibly trigger autism spectrum disorders, ASA hopes to broaden the current paradigm of autism diagnosis and treatment, now focused mostly on behavior and social interaction, to include autism as a condition with treatable medical features. “For too long, parents receive the diagnosis of autism and are told there is nothing that can be done medically. As the evidence presented by these publications shows, children with autism present with medical symptoms that can be treated, which may then improve their abilities to learn, live and maximize their potential,” commented ASA President and CEO Lee Grossman.

Dr. Martha Herbert, Pediatric Neurologist and Assistant Professor at Harvard Medical School and a member of ASA’s Panel of Professional Advisors, explains this paradigm further: "We're saying, yes, autism is biological, but more than genetic...it's more than the brain, it's the whole body, and it's a chronic illness." While genetics have been driving federally-funded research into the disorder, more than genetics is needed to yield answers about autism. "Autism is not simply wired in before you are born," said Dr. Herbert, who along with colleagues has shown abnormal changes that happen in brains of those with autism after birth. "When you include environment, lots of things in autism make more sense," she said. For example, large numbers of children with autism have various forms of gastrointestinal disease, or immune systems that react abnormally. "The gut and immune systems are the body's gateways to the environment, and they are also very connected to the brain." As people see that treating medical problems can help children with autism function better, Herbert said that the new paradigm in autism research should look more at how children with autism can change and improve, and incorporate treatments that can restore the body's resiliency and the brain's ability to adapt.

30 articles cover this important topic. An illustrative list includes:

· Time to Get a Grip - Martha R. Herbert, M.D., Ph.D. (Harvard University)

· Can Exposure to Environmental Toxicants Influence Autism Susceptibility? - Isaac N. Pessah, Ph.D. (M.I.N.D. Institute, UC Davis)

· Autism’s New Paradigm – Michael Lerner, Ph.D. (Commonweal)

· We Can’t Wait – interview with Dr. Thomas Insel (Director, National Institute of Mental Health at NIH)

· Epidemiologic Approaches to Autism and the Environment - Craig J. Newschaffer, Ph.D.

· The Prenatal Environment and Neuroinflammation in Autism – Susan Connors, M.D., Carlos Pardo, M.D. and Andrew Zimmerman, M.D. (Johns Hopkins)

This effort is part of a broader project funded in part by a grant from the John Merck Fund. ASA’s project is overseen by an Advisory Board on Environmental Health, who is undertaking a "campaign of influence" for early 2007 which will build a grassroots community to continue research and awareness of the effect of environmental influences on autism.

To access the website, visit www.autism-society.org/environmental_health.

To schedule an interview with ASA or one of our authors and find out more about this important initiative, please contact Marguerite Colston, Director of Communications, at mcolston@autism-society.org.

About ASA

ASA is the oldest and largest grassroots organization within the autism community. Today, more than 100,000 members and supporters are connected through a working network of nearly 200 chapters nationwide. ASA is dedicated to increasing public awareness about autism and the day-to-day issues faced by individuals with autism, their families and the professionals with whom they interact.

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FOR IMMEDIATE RELEASE:
March 21, 2006

UC DAVIS STUDY WITH MICE LINKS THIMEROSAL WITH IMMUNE SYSTEM DYSFUNCTION

(Sacramento, Calif.) - A team of cell biologists, toxicologists and molecular bioscientists at the University of California, Davis, has published a study connecting thimerosal with disruptions in antigen-presenting cells known as dendritic cells obtained from mice. The study provides the first evidence that dendritic cells show unprecedented sensitivity to thimerosal, resulting in fundamental changes in the immune system's ability to respond to external factors. The study was published online today and will be available in the July print edition of Environmental Health Perspectives, the peer-reviewed scientific publication of the National Institute of Environmental Health Sciences.

"This is the first time that thimerosal has been shown to selectively alter the normal functions of dendritic cells," said Isaac Pessah, a toxicologist with the UC Davis School of Veterinary Medicine, director of the Children's Center for Environmental Health and Disease Prevention and senior author of the study. "Dendritic cells play pivotal roles in overcoming viral and bacterial invaders by coordinating the immune system's overall combat response." One dendritic cell can activate as many as 300 T-cells - white blood cells that help find and kill external agents that attack the immune system - making them the most effective immune system activators.

The study shows how intricate connections between calcium channels in dendritic cells change when exposed to thimerosal. "The slightest fluctuation in how calcium channels 'communicate' can alter the growth, maturation and activation of dendritic cells," explained Pessah. "Thimerosal dramatically alters how two key calcium channels, code-named RyR1 and IP3R1, found in dendritic cells function as a team by 'garbling' the normal signaling system between them."

When thimerosal at a concentration as low as 20 parts per billion alters the fidelity of normal calcium signals, dendritic cells show abnormal secretion of IL-6 cytokine - a potent chemical signal that initiates inflammatory responses. Higher concentrations - 200 parts per billion - causes programmed death of dendritic cells, preventing them from maturing and doing their primary job of activating T-cells. Without proper feedback to guide its response, a normal dendritic cell can quickly become "a rogue, producing misinformation that could activate aberrant and harmful immune responses," Pessah explained. "Even one rogue dendritic cell can activate many inappropriate immune responses."

The research team conducted the study on cells cultured from a strain of mouse not particularly susceptible to immune dysregulation. Using fluorescent stains and powerful microscopes to study both immature and mature dendritic cells from bone marrow cultured under normal physiological conditions, the researchers discovered that extremely small levels of thimerosal interfere significantly with calcium channel function after just a few minutes of exposure. They also observed that immature dendritic cells are particularly sensitive to thimerosal.

Thimerosal is a cheap and effective mercury-based preservative. Its potential effects on embryonic neuron development led to its removal from many pediatric vaccines, however it is still used in influenza, diphtheria and tetanus vaccines, blood products and many over-the-counter pharmaceuticals. The concentrations of thimerosal used by the UC Davis researchers were comparable to those attained in childhood vaccinations containing the preservative.

Researchers and parents have previously proposed links between childhood vaccines and autism, a neurodevelopmental disorder that affects language skills and social interactions. In addition to being a direct neurotoxicant, the UC Davis study indicates that thimerosal may also be an immunotoxicant, leaving the immune system vulnerable to microbes and other external influences.

"Our findings do not directly implicate thimerosal as a single causative agent for triggering neurodevelopmental disorders such as autism," Pessah said. "There is growing evidence that autism is several disorders that we now refer to as just one. There is also growing evidence that some children with autism have unique immune cell composition and responses to antigens. The results of our work provide a framework to test the hypothesis that the genetic background of some individuals may render them especially susceptible to thimerosal."

Other experts also advise drawing no final conclusions regarding thimerosal and autism based on these outcomes.

"These findings should be interpreted cautiously. Although they suggest that thimerosal may affect dendritic cell function, the pathophysiological consequences of thimerosal remain unclear," said David A. Schwartz, a physician and director of the National Institute of Environmental Health Sciences.

Since cell functions can differ across organisms, Pessah will next study dendritic cells isolated from the blood of children with and without autism to confirm if the intercellular changes are the same in humans. The initial mouse study was funded by the National Institute of Environmental Health Sciences and the UC Davis M.I.N.D. Institute. Joining Pessah on the scientific team were molecular bioscientists Samuel R. Goth, Ruth A. Chu and Gennady Cherednichenko and pathologist Jeffrey P. Gregg.

A copy of "Uncoupling of ATP-mediated Calcium Signaling and Dysregulated IL-6 Secretion in Dendritic Cells by Nanomolar Thimerosal" can be downloaded at http://www.ehponline.org/docs/2006/8881/abstract.html.

The NIEHS-funded Center for Children's Environmental Health and Disease Prevention is a multi-disciplinary research organization established to examine how toxic chemicals may influence the development of autism in children. The center's goal is to contribute knowledge about autism that will lead to new prevention and treatment strategies. For more information, visit www.vetmed.ucdavis.edu/cceh. The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center bringing together parents, scientists, clinicians and educators for research on autism and other neurodevelopmental disorders. For more information, visit www.mindinstitute.org.

FOR IMMEDIATE RELEASE:
May 5, 2005

CHILDREN WITH AUTISM HAVE DISTINCTLY DIFFERENT IMMUNE SYSTEM REACTIONS COMPARED TO TYPICAL CHILDREN
Immunologists from UC Davis M.I.N.D. Institute find clear biological component to perplexing childhood neurological disorder

(BOSTON, Mass.) -- A new study by researchers at the University of California, Davis, M.I.N.D. Institute and the NIEHS Center for Children's Environmental Health demonstrate that children with autism have different immune system responses than children who do not have the disorder. This is important evidence that autism, currently defined primarily by distinct behaviors, may potentially be defined by distinct biologic changes as well.

The study was released at the 4th International Meeting for Autism Research (IMFAR) -- a meeting of autism scientists started by Cure Autism Now, the UC Davis M.I.N.D. Institute and the National Alliance for Autism Research to accelerate knowledge of this increasingly common and perplexing disorder. It is estimated that autism now affects 1 in every 166 children.

"Understanding the biology of autism is crucial to developing better ways to diagnose and treat it," said Judy Van de Water, associate professor of rheumatology, allergy and clinical immunology at the UC Davis School of Medicine and the UC Davis M.I.N.D. Institute. "While impaired communication and social skills are the hallmarks of the disorder, there has not yet been strong scientific evidence that the immune system is implicated as well. We now need to design carefully controlled studies that tell us even more about the way in which a dysfunctional immune system may or may not play a role in the disorder itself."

Van de Water, along with co-investigator of the study Paul Ashwood, assistant professor of medical microbiology and immunology at the UC Davis M.I.N.D. Institute, isolated immune cells from blood samples taken from 30 children with autism and 26 typically developing children aged between two and five years of age. The cells from both groups were then exposed to bacterial and viral agents that usually provoke T-cells, B cells and macrophages - primary players in the immune system.

Of the agents tested in the study - tetanus toxoid, lippopolysaccharide derived from E. coli cell walls, a plant lectin known as PHA, and a preparation of the measles, mumps and rubella vaccine antigens - the researchers found clear differences in cellular responses between patients and controls following exposure to the bacterial agents and PHA.

In response to bacteria, the researchers saw lower levels of protein molecules called cytokines in the group with autism. Cytokines function as mediators of the immune response, carrying messages between B, T and other immune cells. They also are known to be capable of having profound effects on the central nervous system, including sleep and the fever response. Immune system responses to PHA, in contrast, produced more varied cytokine levels: Higher levels of certain cytokines and lower levels of others.

According to Van de Water and Ashwood, these studies illustrate that under similar circumstances, the cytokine responses elicited by the T-cells, B-cells, and macrophage cell populations following their activation differs markedly in children with autism compared to age-matched children in the general population. Cytokines are known to affect mood and behavior, and while their specific role in the development of autism remains unclear, the potential connection is an intriguing area of research that warrants further investigation.

"This study is part of a larger effort to learn how changes in immune system response may make some children more susceptible to the harmful effects of environmental agents," said Kenneth Olden, director of the National Institute of Environmental Health Sciences, the federal agency that provided funding for the study. "A better understanding of the connection between altered immune response and autism may lead to significant advances in the early detection, prevention and treatment of this complex neurological disorder."

"We would like to take these findings and explore whether, for example, the cytokine differences are specific to certain subsets of patients with autism, such as those with early onset, or those who exhibit signs of autism later during development," Ashwood said. He added that the logical next step is to look directly at specific cell populations that may be responsible for the diverging responses between patients and controls.

This study was supported by grants from the National Institutes of Environmental Health Sciences, the U.S. Environmental Protection Agency, the UC Davis M.I.N.D. Institute, Ted Lindsay Foundation and Visceral. The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center for research into the causes and treatments of autism, bringing together parents, scientists, clinicians and educators. For further information, go to http://www.ucdmc.ucdavis.edu/mindinstitute.