Saturday, January 23, 2010

Brain Imaging May Help Diagnose Autism

Children with autism spectrum disorders (ASDs) process sound and language a fraction of a second slower than children without ASDs, and measuring magnetic signals that mark this delay may become a standardized way to diagnose autism.

Researchers at The Children's Hospital of Philadelphia report their findings in an online article in the journal Autism Research, published today.

"More work needs to be done before this can become a standard tool, but this pattern of delayed brain response may be refined into the first imaging biomarker for autism," said study leader Timothy P.L. Roberts, Ph.D., vice chair of Radiology Research at Children's Hospital.

ASDs are a group of childhood neurodevelopmental disorders that cause impairments in verbal communication, social interaction and behavior. ASDs are currently estimated to affect as many as one percent of U.S. children, according to a recent CDC report.

Like many neurodevelopmental disorders, in the absence of objective biological measurements, psychologists and other caregivers rely on clinical judgments such as observations of behavior to diagnose ASDs, often not until a child reaches school age. If researchers can develop imaging results into standardized diagnostic tests, they may be able to diagnose ASDs as early as infancy, permitting possible earlier intervention with treatments. They also may be able to differentiate types of ASDs (classic autism, Asperger's syndrome or other types) in individual patients.

In the current study, Roberts and colleagues used magnetoencephalography (MEG), which detects magnetic fields in the brain, similar to the way electroencephalography (EEG) detects electrical fields. Using a helmet that surrounds the child's head, the team presents a series of recorded beeps, vowels and sentences. As the child's brain responds to each sound, noninvasive detectors in the MEG machine analyze the brain's changing magnetic fields.

The researchers compared 25 children with ASDs, having a mean age of 10 years, to 17 age-matched typically developing children. The children with ASDs had an average delay of 11 milliseconds (about 1/100 of a second) in their brain responses to sounds, compared to the control children. Among the group with ASDs, the delays were similar, whether or not the children had language impairments.

"This delayed response suggests that the auditory system may be slower to develop and mature in children with ASDs," said Roberts. An 11-millisecond delay is brief, but it means, for instance, that a child with ASD, on hearing the word 'elephant' is still processing the 'el' sound while other children have moved on. The delays may cascade as a conversation progresses, and the child may lag behind typically developing peers."

A 2009 study by Roberts and colleagues sheds light on how changes in brain anatomy may account for the delays in sound processing. The study team used MEG to analyze the development of white matter in the brains of 26 typically developing children and adolescents. Because white matter carries electrical signals in the brain, signaling speed improves when neurons are better protected with an insulating sheath of a membrane material called myelin.

In this previous study, the researchers showed that normal age-related development of greater myelination corresponds with faster auditory responses in the brain. "The delayed auditory response that we find in children with ASDs may reflect delayed white matter development in these children," said Roberts.

Roberts says his team's further studies will seek to refine their imaging techniques to determine that their biomarker is specific to ASDs, and will investigate other MEG patterns found in children with ASDs in addition to auditory delays.

Grants from National Institute of Health, the Nancy Lurie Marks Family Foundation, Autism Speaks, and the Pennsylvania Department of Health supported this research. In addition, Roberts holds an endowed chair, the Oberkircher Family Chair in Pediatric Radiology at The Children's Hospital of Philadelphia. Roberts' co-authors were from Children's Hospital, including the Hospital's Center for Autism Research.

Friday, January 22, 2010

Recent Rise In Certain Disorders Could Be Explained By Ongoing Human Evolution

The subtle but ongoing pressures of human evolution could explain the seeming rise of disorders such as autism, autoimmune diseases, and reproductive cancers, researchers write in the Proceedings of the National Academy of Sciences. Certain adaptations that once benefited humans may now be helping such ailments persist in spite of - or perhaps because of - advancements in modern culture and medicine.

"This work points out linkages within the plethora of new information in human genetics and the implications for human biology and public health, and also illustrates how one could teach these perspectives in medical and premedical curricula," says author Peter Ellison, John Cowles Professor of Anthropology at Harvard University.

Ellison's co-authors are Stephen Stearns of Yale University, Randolph Nesse of the University of Michigan, and Diddahally Govindaraju of the Boston University School of Medicine. The research was first presented at the Arthur M. Sackler Colloquium, co-sponsored by the National Academy of Science and the Institute of Medicine.

Colloquium presentations described in the current paper include research suggesting that:

* Autism and schizophrenia may be associated with the over-expression of paternally or maternally derived genes and influences, a hypothesis advanced by Bernard Crespi of Simon Fraser University.

* Maternal and paternal genes engage in a subtle tug-of-war well into childhood with consequences for childhood development, as posited by David Haig, George Putnam Professor of Organismic and Evolutionary Biology at Harvard.

* Humans may be susceptible to allergies, asthma, and autoimmune diseases because of increased hygiene, according to Kathleen Barnes of Johns Hopkins University. Without being exposed to intestinal worms and parasites, as our ancestors were, our immune systems are hypersensitive.

* Natural selection still influences our biology, despite advances in modern culture and medicine. Stearns found that natural selection favors heavier women and reduces the age at which a woman has her first child.

In the final presentation of the colloquium, researchers called for the integration of evolutionary perspectives into medical school curricula, to help future physicians consider health problems from an evolutionary perspective.

"We're trying to design ways to educate physicians who will have a broader perspective and not think of the human body as a perfectly designed machine," says Ellison. "Our biology is the result of many of evolutionary trade-offs, and understanding these histories and conflicts can really help the physician understand why we get sick and what we might do to stay healthy."

Previous work in evolutionary medicine helped explain why disease is so prevalent and difficult to prevent - because natural selection favors reproduction over health, biology evolves more slowly than culture, and pathogens evolve more quickly than humans.

"I think that the main take-home point is that evolution and medicine really do have things to say to each other, and some of these insights actually reduce suffering and save lives," says Stearns.

High Rates Of Birth Defects Found In Autistic Children

Nearly two-thirds of the children with Autistic Spectrum Disorders recorded in the National Birth Defect Registry (NBDR) also suffer from structural birth defects, according the national nonprofit, Birth Defect Research for Children (BDRC). The group reported that most of the defects affect the face, head and central nervous systems of newborns.

Birth Defect Research for Children, a national nonprofit founded in 1982, maintains the registry to collect data from parents on all kinds of structural birth defects and functional deficits including autistic spectrum disorders. Betty Mekdeci, executive director of BDRC explains, "We designed the registry with a collaboration of prominent scientists. The registry's extensive data allows researchers to identify possible patterns underlying the incidence of birth defects as well as prenatal conditions and exposures. We are asking all parents of children with structural and functional birth defects to contact us to register for our database to continue this study."

"Our current data suggests that genetic and environmental triggers may interact to account for the increase in ASDs. We need to collect more data to confirm the pattern we are seeing."

The new analysis reveals that over 60% cases also had structural birth defects, primarily Central Nervous System (CNS) or Craniofacial Defects. The other 40% of the ASD cases reported associated developmental problems, but no reported structural birth defects.

Most frequent CNS disorders reported were Microcephaly (small head), Cerebral Palsy, Chiari Malformation (a structural defect of the brain) and Absent or Thin Corpus Callosum (the band connecting the two halves of the brain), The most frequent Craniofacial Defects included Low Set Ears, Partial Hearing Loss, Abnormal Teeth and Abnormal Facial Structure.

The registry also collects data on prenatal exposures to medications, illnesses and toxins. The most frequently reported maternal exposure was acetaminophen (AP). AP use has increased in recent years. Recent studies have reported associations between maternal AP ingestion and childhood asthma and a stomach defect called gastroschisis.

Scientific Learning's Fast ForWord Software Approved By Australian Government As Intervention For Children With Autism

Scientific Learning Corp. (NASDAQ:SCIL) today announced that the Australian Government's Department of Families, Housing, Community Services and Indigenous Affairs has named the Fast ForWord ® family of products as an approved intervention for children under age six who are diagnosed with Autism Spectrum Disorders (ASDs).

Designed to accelerate learning by developing the student brain to process more efficiently, the Fast ForWord educational software consists of scientifically proven, intervention programs that apply neuroscience principles to build the fundamental cognitive skills required to read and learn. The strengthening of these skills results in a wide range of improved critical language and reading abilities, such as phonological awareness, phonemic awareness, fluency, vocabulary, comprehension, decoding, working memory, syntax and grammar.

In Australia, the Fast ForWord program is available to eligible children under the Helping Children with Autism funding package. Through this package, the Australian Government is working to address the need for support and services for children with ASDs. As part of the package, the government offers funding for early intervention services for children ages zero to seven who are diagnosed with an ASD. Eligible families can access the Fast ForWord program from Scientific Learning's two Value Added Representative (VAR) organizations in Australia, LearnFast Australia/Lindfield Speech Pathology & Learning Center in Sydney, New South Wales and Sonic Learning in Perth.

Communication Problems In The Brain

Maturation disorders of nerve terminals may trigger autism; researchers in Heidelberg publish in the Proceedings of the National Academy of Sciences

For brain cells to communicate, the contacts to each other must function. The protein molecule neuroligin-1 plays an important role in this as it stimulates the necessary maturation processes at the contact sites (synapses) of the nerves. A synaptic maturation disorder is possibly involved in the development of autism. Dr. Thomas Dresbach and his team from the Institute for Anatomy and Cell Biology at the University of Heidelberg, in cooperation with the study group led by Professor Dr. Thomas Kuner at the same institute and Professor Dr. Nils Brose, Max Planck Institute for Experimental Medicine in Göttingen, have published their results in the prestigious international journal PNAS (Proceedings of the National Academy of Sciences).

One hundred billion nerve cells make our brain a thinking machine. Each of these nerve fibers produces a long extension, the axon, which terminates in numerous small knobs. Transmitters are released here that transfer information to the next nerve cell. The contact site between nerve ending and adjacent nerve cell is called a synapse. The number and location of active synapses determine which areas of the brain are especially active at a given time.

Neuroligin-1 protein necessary for maturation

The synapses of young nerve cells must mature before they can release their neurotransmitters to the full extent. Researchers were able to show using genetically modified nerve cells from mice that the postsynaptic nerve cell, the receptor, must form a sufficient amount of a certain protein molecule, neuroligin-1, to allow this maturation process to take place. In addition, the nerve endings from where information is sent must release slight amounts of neurotransmitters to stimulate the neuroligin in the postsynaptic nerve cell.

"A fully functioning contact can develop only if both sides, transmitter and receptor of information, are involved in the maturation process," explained Dr. Dresbach. If no neuroligin-1 is formed, the nerve endings remain at an immature stage and release fewer neurotransmitters; the flow of information is interrupted. The nerve endings can only whisper, so to speak.

Autism caused by a malfunction at the synapses?
"The results are significant for actual concepts about how autism develops," says Professor Dr. Joachim Kirsch, director of the Institute for Anatomy and Cell Biology. Symptoms of autism are first noticed in early childhood as an information processing disorder. The symptoms may be more or less pronounced, but all patients display weaknesses in social contacts and communication. "There are many indications that malfunctions of synaptic molecules are involved in the development of this illness. It has thus far been unclear exactly what these malfunctions are, but we now know what to look for," says Professor Kirsch. The study was funded by the FRONTIER program of the excellence initiative at the University of Heidelberg.

Rate Of Autism Disorders Climbs To 1 Percent Among 8 Year Olds

Autism and related development disorders are becoming more common, with a prevalence rate approaching 1 percent among American 8-year-olds, according to new data from researchers at the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC).

The study is a partnership between UAB, the CDC and 10 other U.S. research sites. It shows that one in 110 American 8-year-olds is classified as having an autism spectrum disorder (ASD), a 57 percent increase in ASD cases compared to four years earlier.

The new findings, published Dec. 18 in the CDC's Morbidity and Mortality Weekly Report (MMWR), highlight the need for social and educational services to help those affected by the condition, said Beverly Mulvihill, Ph.D., a UAB associate professor of public health and co-author on the study.

ASDs are a group of developmental disabilities such as autism and Asperger disorder that are characterized by delays or changes in childhood socialization, communication and behavior.

"This is a dramatic increase in the number of kids classified as autistic or documented on the spectrum of similar disorders," Mulvihill said. "It is not entirely clear what is causing the rise, but we know major collaborative efforts are needed to improve the understanding and lives of people and families impacted."

The MMWR study discusses possible factors that might contribute to the increase in ASD cases. They include a broader definition of autism disorders and a heightened awareness of ASD by parents, doctors, educators and other professionals. The findings do not address whether or not any of the increase is attributable to a true increase in the risk of developing ASD, more frequent and earlier diagnoses, and other factors.

Data comes from the Autism and Developmental Disabilities Monitoring (ADDM) Network, a collection of 11 sites in Alabama, Arizona, Colorado, Florida, Georgia, Maryland, Missouri, North Carolina, Pennsylvania, South Carolina and Wisconsin. ADDM reviewers are uniformly trained to review and confirm cases; some children included in the study have documented ASD symptoms but never received a diagnosis.

The study also found that boys are 4.5 times more likely than girls to have ASD, a finding that confirms earlier studies, says Martha Wingate, Dr.P.H., a UAB assistant professor of public health and study co-author.

"It still is not clear why males more frequently are affected," Wingate said. "One thing we know for sure is that more research is needed to quantify the effects of single or multiple factors such as diagnosis patterns, inclusion of milder cases and other components."

The ADDM sites are not selected based on any statistical pattern, but the 300,000-plus children included in the study represent 8 percent of the nation's 8-year-olds.

The Alabama Autism Surveillance Project, located within the UAB Department of Health Care Organization and Policy, is a member of the ADDM network. Funding for the project is from the CDC's National Center for Birth Defects and Developmental Disabilities Division.

About the UAB School of Public Health

The School of Public Health is a community of scholars and professionals working and teaching in varied arenas of public health with the goal of fostering research and best practices crucial to the health of our nation and its peoples. The school offers more than 20 areas of study and manages dozens of research and community-service centers.

Landmark Consensus Articles Published In Pediatrics Acknowledge The Need To Improve Treatment Of Gastrointestinal Disorders In Individuals With Autism

A causal relationship between gastrointestinal disorders and the behavioral features of children with autism spectrum disorder has been acknowledged for years by parents caring for those affected, yet dismissed by mainstream medicine. A landmark paper, Recommendations for Evaluation and Treatment of Common Gastrointestinal Problems in Children with ASDs, a consensus report published this week in Pediatrics, is an important step forward in closing this gap. Acknowledging that certain behavioral manifestations of patients with ASD such as self-injury and poor sleep might have a GI basis is the first step toward achieving substantive therapies.

Because it was felt that many individuals with ASD might have undiagnosed medical conditions, often involving the gastrointestinal tract, representatives from the Autism Research Institute (ARI) and other autism advocacy groups worked to convene a gut consensus meeting from which the articles were derived. On May 29-30, 2008, a multidisciplinary panel of 27 clinical and research experts met in Boston, Massachusetts to develop recommendations for the evaluation and treatment of GI disorders in individuals with ASD.

ARI's Director Dr. Stephen Edelson commented, "This is truly a human rights issue; every child deserves proper medical attention--whether or not they have autism. This published report brings much-needed focus to gastrointestinal problems that are commonly associated with the autism spectrum. The conclusions of the report are clear: physicians need to be alert and responsive to such problems when treating these patients; additional research on prevalence, cause, and appropriate treatment is imperative."

Parents and physicians should be on the lookout for the most common GI symptoms reported in people with ASD: chronic constipation, abdominal pain with or without diarrhea, reflux, and abdominal bloating. Problem behaviors such as self-injury and aggression, as well as overall changes such as sleep disturbance or irritability, might be indicators of stomach pain. The authors concluded that "The approach to evaluation and diagnosis of possible underlying medical conditions, in particular GI disorders, should be no different from the standard of care for persons without ASD."

First Step Toward Needed Guidelines For Children With Autism Provided By Pediatrics Gastrointestinal Consensus Statement And Recommendations

Autism Speaks applauds the consensus statement and recommendations for the evaluation, diagnosis, and treatment of gastrointestinal (GI) disorders in children with autism spectrum disorders (ASD) released online in Pediatrics as one step in advancing physician awareness of unique challenges in the medical management of children with autism. "We are pleased to see the publication of these consensus recommendations. Autism Speaks' current efforts will take this further by creating evidence-based guidelines for physicians. The goal is to develop a comprehensive care model that will guide physicians in addressing a wide range of medical issues, including GI problems, that many individuals with autism suffer from," commented Geraldine Dawson, Ph.D., Autism Speaks chief science officer.


The two reports published today present outcomes of a meeting held in May 2008, sponsored by the Autism Forum, in which working groups participating in the meeting reviewed current evidence on the evaluation and treatment of GI disorders specifically for children with autism. The 2008 meeting from which these consensus recommendations were derived recognized that health care practitioners severely lack solid information to guide care of children with autism and GI problems and there is a need for more research data, including genetic research, as a prerequisite to develop evidence-based guidelines specific to autism.


"The Pediatrics paper represents long-sought recognition by the mainstream medical community that treatment of GI problems in children with autism requires specific and specialized approaches," reacted Dr. Dawson. "Autism Speaks has been actively engaged in the study of GI problems associated with children with autism, working toward enhanced medical community awareness for over five years through its research agenda and the Autism Speaks' Autism Treatment Network (ATN)."


Dan Coury, M.D., ATN medical director, commented, "We are delighted to see the publication of important information that can support clinicians and caregivers in providing better care for children with autism, particularly with GI concerns, as parents unfortunately very often find it difficult to identify physicians who have an understanding of these issues and are able to provide appropriate medical care for their children. GI and pediatric specialists from six of the ATN sites participated in the forum and in the development of these recommendations, which shows the power of interaction among the communities and individuals dedicated to this problem. Autism Speaks is already engaged in the crucial next step which is to move beyond these consensus-based recommendations to develop evidence-based clinical guidelines." In addition to development of evidence-based clinical guidelines for GI issues, the ATN is also currently working on evidence based clinical guidelines for medical management of sleep, and neurologic disorders associated with autism. "Delivery of evidence-based clinical guidelines will serve as excellent opportunities for future training and education of physicians," added Dr. Dawson.


The consensus statement highlights several important themes, the first emphasizing that GI problems are a genuine concern in the ASD population and that these disorders exacerbate or contribute to problem behaviors. The need for awareness of how GI problems manifest in children with autism and the potential for accompanying nutritional complications and impaired quality of life were also emphasized.


In the second paper, the authors make consensus recommendations providing guidance on how current general pediatric standards of care that can and should be applied for children with ASD. George Fuchs, M.D., a co-author on the two papers and chair of the ATN GI Committee remarked, "The recommendations provide important guidance for the clinician to adapt the current practices of care (for abdominal pain, chronic constipation and gastroesophageal reflux) for the child with autism. The recommendations from the Autism Forum meeting complement the ATN's on-going work to develop evidence-based, ASD-specific guidelines. The ATN is currently piloting newly created guidelines and monitoring their effectiveness. We anticipate this data will contribute to an evidence-based foundation to support best practices for GI problems in ASD."


Autism Speaks is committed to the sustained support of efforts that address co-morbid medical conditions in the ASD population. In recognizing that there's not enough evidence in any GI area and more research is needed, the Pediatric papers reaffirm the importance of the recent November 2009, Autism Speaks sponsored symposium and workshop on Gastrointestinal Disorders in Autism Spectrum Disorders. The symposium and workshop represented an important partnership with the American Academy of Pediatrics, and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) - the largest professional society for GI and nutritional specialists, and a professional authority for the development and implementation of pediatric GI guidelines. The symposium raised awareness and provided the latest scientific information to an audience of 168 researchers, clinicians, and pediatric GI and nutrition specialists, most of whom had limited expertise in autism. The symposium was followed by a workshop that brought together a diverse group of experts in GI, nutrition, pediatrics, pain, ASD, and biological research. Recommendations were developed for an expanded and targeted research agenda for the field that will address current gaps in the knowledge base and aim to advance evaluation and treatment of ASD-GI disorders. Proceedings from the meeting are scheduled to be published in 2010. A unique and important element in both the Symposium and Workshop was the inclusion of parents of children with ASD.

University Of California Davis Researchers Identify Autism Clusters In California

Researchers at UC Davis have identified 10 locations in California where the incidence of autism is higher than surrounding areas in the same region. Most of the areas, or clusters, are in locations where parents have higher-than-average levels of educational attainment. Because children with more educated parents are more likely to be diagnosed with an autism spectrum disorder, one need look no further for a cause, the authors say. The other clusters are located close to major autism treatment centers.

The clusters are located primarily in the high-population areas of Southern California and, to a lesser extent, in the San Francisco Bay Area. The researchers said that, while children born within the clusters during the study period were more likely to be diagnosed with autism, the majority of the state's children with autism were born in adjacent areas outside the clusters.

For the rigorous study, published online today in the journal Autism Research, scientists examined nearly all of the approximately 2-1/2 million births recorded in the state of California from 1996 through 2000. About 10,000 children born during that five-year period were later diagnosed with an autism spectrum disorder, according to the California Department of Developmental Services (DDS).

After mapping the state's birth cohort based on where the mothers lived at the time when their children were born, the researchers pinpointed birth locations of children who were later diagnosed with autism. The study looked for areas of higher incidence within each of the service zones of DDS's regional centers, which coordinate services for individuals with developmental disorders like autism.

"This is the first time that anyone has looked at the geography of autism births in California in order to see whether there might be some local patches of elevated environmental risk. This method ignores unknown widespread factors (such as a regional pollutant) that could increase autism incidence," said Karla Van Meter, the study's lead author. Van Meter is an epidemiologist and was a doctoral student in the UC Davis Department of Public Health Sciences and at the Center for Animal Disease Modeling and Surveillance when the study was conducted.

"This spatial study was extremely rigorous because we developed a methodology that greatly improved accuracy in identifying areas of higher autism incidence. With so many possible environmental health risk factors, we see this method as generally useful for focusing studies on exposures that are elevated in such clusters," Van Meter said.

However, the researchers said that in this investigation the clusters probably are not correlated with specific environmental pollutants or other "exposures." Rather, they correlate to areas where residents are more educated.

"What we found with these clusters was that they correlated with neighborhoods of high education or neighborhoods that were near a major treatment center for autism," said senior author Irva Hertz-Picciotto, a professor of public health sciences and a researcher with the UC Davis MIND Institute.

"In the U.S., the children of older, white and highly educated parents are more likely to receive a diagnosis of autism or autism spectrum disorder. For this reason, the clusters we found are probably not a result of a common environmental exposure. Instead, the differences in education, age and ethnicity of parents comparing births in the cluster versus those outside the cluster were striking enough to explain the clusters of autism cases," Hertz-Picciotto said.

Autism is a neurodevelopmental disability characterized by impaired social development and communication and restricted, repetitive behaviors. It is considered a lifelong condition that develops by the time a child is 3 years old. The researchers limited their study to the five-year period between 1996 and 2000 in order to allow all of the children born during that time to grow to an age by which they probably would have received a diagnosis - 6 years old.

Van Meter said that the increased risk of autism in these areas is roughly a doubling of the incidence of autism over the incidence in the surrounding zone. For example, for the cluster area located in the service zone of the San Diego Regional Center, the autism incidence was 61.2 per 10,000 births and, in the rest of the Regional Center service zone, 27.1 per 10,000 births. For the Harbor Regional Center the incidence was 103.4 and 57.8, respectively. Van Meter added that it is important to remember that most of the children with autism were not born in the cluster areas.

In Southern California, the areas of increased incidence were located within these Regional Center service zones:

1. The Westside Regional Center, headquartered in Culver City, Calif., which serves the communities of western Los Angeles County, including the cities of Culver City, Inglewood and Santa Monica;

2. The Harbor Regional Center, headquartered in Torrance, Calif., which serves southern Los Angeles County, including the cities of Bellflower, Harbor, Long Beach and Torrance;

3. The North Los Angeles County Regional Center, headquartered in Van Nuys, Calif., which serves the San Fernando and Antelope valleys - two clusters were located in this regional center's service zone.

4. The South Central Los Angeles Regional Center, headquartered in Los Angeles, which serves the communities of Compton and Gardena;

5. The Regional Center of Orange County, headquartered in Santa Ana, Calif., which serves the residents of Orange County; and

6. The Regional Center of San Diego County, headquartered in San Diego, which serves people living in Imperial and San Diego counties.

In Northern California, the areas of increased incidence were located within these regional centers' service zones:

7. The Golden Gate Regional Center, headquartered in San Francisco, which serves Marin and San Mateo counties and the City and County of San Francisco. Two clusters were located within the Golden Gate Regional Center's service zone; and

8. The San Andreas Regional Center, headquartered in Campbell, Calif., which serves Santa Clara, Santa Cruz, Monterey and San Benito counties.

Two areas of increased incidence were located in Central California regional centers' service zones:

9. The Central Valley Regional Center, headquartered in Fresno, Calif., which serves Fresno, Kings, Madera, Mariposa, Merced and Tulare counties; and

10. The Valley Mountain Regional Center, headquartered in Stockton, Calif., which serves Amador, Calaveras, San Joaquin, Stanislaus and Tuolumne counties.

The South Central Los Angeles and Valley Mountain Regional Center autism clusters were listed as "potential clusters" because their clusters met a reduced set of statistical conditions.

All of these areas were identified using a sophisticated new biostatistical testing procedure developed by Van Meter in collaboration with study co-author Lasse Christiansen and constructed on Christiansen's earlier statistical work. This method looked for combinations of events, in this case, autism, within a set of locations, in this case, births, whose occurrence would not be expected to occur at random. This is the first application of that method. UC Davis undertook the epidemiological study as a step toward identifying geographic risk factors for autism in California, Van Meter said.

The study also examined demographic factors recorded on the children's birth records that are known to be associated with both autism and residential location. These included having an older parent - a known autism risk factor. The researchers found a statistically significant but small association of the cluster areas with older parental age at the time their child was born.

Hertz-Picciotto said that the findings do not counter the idea that the environment plays a role in autism, but rather, help to focus attention toward certain types of exposures.

"Because of the strong link between demographics, particularly parental education, and the locations of clusters, other explanations for these pockets of high autism incidence, such as localized sources of exposure, are not likely," Van Meter explained.

"The risk for a child with highly educated parents to be diagnosed with autism is probably not caused by the location of the mother's residence or any local shared environmental exposures," she said. "Our result indicates that the most likely sources of environmental hazards for autism in California are in or around the home or else are widespread."

"The strong link between demographics, particularly parental education, and the locations of the clusters validated the effectiveness of the statistical method that we employed because it successfully identified areas where a known risk factor was concentrated," she added.