RxPG News : Autism

Behavioural signs of autism become evident between the ages of 6 and 12 months

Tue, 16 Feb 2010 14:04:40 PST

( from http://www.rxpgnews.com ) A study of the development of autism in infants, comparing the behavior of the siblings of children diagnosed with autism to that of babies developing normally, has found that the nascent symptoms of the condition — a lack of shared eye contact, smiling and communicative babbling — are not present at 6 months, but emerge gradually and only become apparent during the latter part of the first year of life.

Researchers conducted the study over five years by painstakingly counting each instance of smiling, babbling and eye contact during examinations until the children were 3. They found that by 12 months the two groups’ development had diverged significantly. Intentional social and communicative behavior among children developing normally increased while among infants later diagnosed with autism it decreased dramatically. The study is published online early and will appear in the March issue of the Journal of the American Academy of Child & Adolescent Psychiatry.

“This study provides an answer to when the first behavioral signs of autism become evident,” said Sally Ozonoff, the study’s lead author, a professor of psychiatry and behavioral sciences and a researcher with the UC Davis MIND Institute. “Contrary to what we used to think, the behavioral signs of autism appear later in the first year of life for most children with autism. Most babies are born looking relatively normal in terms of their social abilities but then, through a process of gradual decline in social responsiveness, the symptoms of autism begin to emerge between 6 and 12 months of age.”

Autism is a pervasive developmental disorder of deficits in social skills and communication, as well as in repetitive and restricted behaviors, with onset occurring prior to age 3. Abnormal brain development, probably beginning prenatally, is known to be fundamental to the behaviors that characterize autism. Current estimates place the condition’s incidence at between 1 in 100 and 1 in 110 children in the United States.

Children with a sibling already diagnosed with autism are known to be among those at greatest risk of developing the disorder. The current study included 25 high-risk children who met criteria for autism at 3 years of age, matched with 25 low-risk peers who were developing normally. It was conducted at the MIND Institute and the University of California, Los Angeles. The sole inclusion criterion for the high-risk group was having a sibling with autism; low-risk participants had to have been born after 36 weeks gestation and have no autistic family members.

The children’s development was evaluated at 6, 12, 18, 24 and 36 months of age using a series of widely implemented diagnostic tools, including the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). Examiners were not told which babies were at high- or low-risk when evaluating the participants’ development.

The researchers found that there were few discernable differences between the two groups at the outset but that after six months, 86 percent of the infants who developed autism showed declines in social communication that were outside the range for typical development. “After six months,” the study found, “the autism spectrum disorder group showed a rapid decline in eye contact, social smiling, and examiner-rated social responsiveness.” Group differences were significant by 12 months in eye contact and social smiling and all other measures by 18 months, the study found.

The study is notable because of the accuracy and precision of its prospective methodology, assiduously recording exact numbers of social and communicative behaviors during lab visits. Previously, researchers have constructed evidence of autism’s earliest manifestations by interviewing parents about when they believed their children’s symptoms first arose or by reviewing home movies for clues to when children begin exhibiting symptoms of autism.

"Until now, research has relied on asking parents when their child reached developmental milestones. But that can be really difficult to recall, and there is a phenomenon called the “telescoping effect” where people usually say that they remember something happening more recently than when it occurred,” Ozonoff said. In addition parents frequently will turn off the video camera when their children are behaving poorly — precisely when autistic symptoms may appear.

Ozonoff said that the study provides a deeper understanding for parents, caregivers and health-care providers and for future research of the developmental trajectory for very young children with autism.

“We need to be careful about how we screen, and we need to know what we’re looking for,” Ozonoff said. “This study tells us that screening for autism early in the first year of life probably is not going to be successful because there isn’t going to be anything to notice. It also tells us that we should be focusing on social behaviors in our screening, since that is what declines early in life.”

“This study also found that the loss of skills continues into the second and third year of life,” she said. “So it may not be adequate, as the American Academy of Pediatrics currently suggests, that providers screen for autism twice before the end of the second year. Autism has a slow, gradual onset of symptoms, rather than a very abrupt loss of skills.”

“Screening may need to continue into the third year of life, since symptom emergence takes place over a long time. If a child starts exhibiting a declining trajectory and a sustained reduction in social communication we want to refer them into therapy, especially if they are at risk,” Ozonoff said, “even before we might be able to make a definitive diagnosis.”

Ozonoff said that the study does not address the etiology of autism or causality. In this study, the infants who participated were at high risk due to having strong family histories of autism, suggesting that genetics plays a major role in the later autism diagnoses, despite the fact that their symptoms were not apparent at birth.

Autism clusters indentified in California

Mon, 04 Jan 2010 22:14:12 PST

( from http://www.rxpgnews.com ) 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.

Increase in the number of children born in California with autism

Thu, 08 Jan 2009 12:44:53 PST

( from http://www.rxpgnews.com ) A study by researchers at the UC Davis M.I.N.D. Institute has found that the seven- to eight-fold increase in the number children born in California with autism since 1990 cannot be explained by either changes in how the condition is diagnosed or counted — and the trend shows no sign of abating.

Published in the January 2009 issue of the journal Epidemiology, results from the study also suggest that research should shift from genetics to the host of chemicals and infectious microbes in the environment that are likely at the root of changes in the neurodevelopment of California’s children.

“It’s time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California,” said UC Davis M.I.N.D. Institute researcher Irva Hertz-Picciotto, a professor of environmental and occupational health and epidemiology and an internationally respected autism researcher.

Hertz-Picciotto said that many researchers, state officials and advocacy organizations have viewed the rise in autism's incidence in California with skepticism.

The incidence of autism by age six in California has increased from fewer than nine in 10,000 for children born in 1990 to more than 44 in 10,000 for children born in 2000. Some have argued that this change could have been due to migration into California of families with autistic children, inclusion of children with milder forms of autism in the counting and earlier ages of diagnosis as consequences of improved surveillance or greater awareness.

Hertz-Picciotto and her co-author, Lora Delwiche of the UC Davis Department of Public Health Sciences, initiated the study to address these beliefs, analyzing data collected by the state of California Department of Developmental Services (DDS) from 1990 to 2006, as well as the United States Census Bureau and state of California Department of Public Health Office of Vital Records, which compiles and maintains birth statistics.

Hertz-Picciotto and Delwiche correlated the number of cases of autism reported between 1990 and 2006 with birth records and excluded children not born in California. They used Census Bureau data to calculate the rate of incidence in the population over time and examined the age at diagnosis of all children ages two to 10 years old.

The methodology eliminated migration as a potential cause of the increase in the number of autism cases. It also revealed that no more than 56 percent of the estimated 600-to-700 percent increase, that is, less than one-tenth of the increased number of reported autism cases, could be attributed to the inclusion of milder cases of autism. Only 24 percent of the increase could be attributed to earlier age at diagnosis.

“These are fairly small percentages compared to the size of the increase that we’ve seen in the state,” Hertz-Picciotto said.

Hertz-Picciotto said that the study is a clarion call to researchers and policy makers who have focused attention and money on understanding the genetic components of autism. She said that the rise in cases of autism in California cannot be attributed to the state’s increasingly diverse population because the disorder affects ethnic groups at fairly similar rates.

“Right now, about 10 to 20 times more research dollars are spent on studies of the genetic causes of autism than on environmental ones. We need to even out the funding,” Hertz-Picciotto said.

The study results are also a harbinger of things to come for public-health officials, who should prepare to offer services to the increasing number of children diagnosed with autism in the last decade who are now entering their late teen years, Hertz-Picciotto said.

“These children are now moving toward adulthood, and a sizeable percentage of them have not developed the life skills that would allow them to live independently,” she said.

The question for the state of California, Hertz-Picciotto said, will become: 'What happens to them when their parents cannot take care of them?'

“These questions are not going to go away and they are only going to loom larger in the future. Until we know the causes and can eliminate them, we as a society need to provide those treatments and interventions that do seem to help these children adapt. We as scientists need to improve available therapies and create new ones,” Hertz-Picciotto said.

Hertz-Picciotto and her colleagues at the M.I.N.D Institute are currently conducting two large studies aimed at discovering the causes of autism. Hertz-Picciotto is the principal investigator on the CHARGE (Childhood Autism Risk from Genetics and the Environment) and MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) studies.

CHARGE is the largest epidemiologic study of reliably confirmed cases of autism to date, and the first major investigation of environmental factors and gene-environment interactions in the disorder. MARBLES is a prospective investigation that follows women who already have had one child with autism, beginning early in or even before a subsequent pregnancy, to search for early markers that predict autism in the younger sibling.

“We’re looking at the possible effects of metals, pesticides and infectious agents on neurodevelopment,” Hertz-Picciotto said. “If we’re going to stop the rise in autism in California, we need to keep these studies going and expand them to the extent possible.”

Ordinary Words Hardly Recognised in Autism

Fri, 04 May 2007 03:09:38 PST

( from http://www.rxpgnews.com ) New research indicates that young children with autism have a difficult time recognizing ordinary words and more of their brains are occupied with this kind of task compared to typically developing youngsters.

âRather than becoming an expert in recognizing words, their brains slow down,â said Patricia Kuhl, co-director of the University of Washingtonâs Institute for Learning and Brain Sciences and an expert in how babies acquire language. âBecause these children canât distinguish what should be a familiar word their brains work too hard and they are unable to focus on new words. When they canât understand a word, they miss everything else that follows in a sentence.â

The research is part of an effort to understand why language disorders are a characteristic of children with autism as scientists begin to peer inside the brains of some of these children to understand whatâs behind their language deficits.

She and her colleagues placed caps fitted with 20 sensors on the heads of the children and recorded brain waves that âleaked through their scalpâ as the babies listened to familiar words (ball, dog, cat, book) and words that would be unfamiliar (verb, pint, bide, rate). The children also were exposed to common words that were recorded and played backwards. Backwards words produce sound patterns that are not characteristic of any language.

The brains of typically developing infants responded with a unique pattern of activation for each of these types of words. The responses for known and unknown words were markedly different. With the backward words, the childrenâs brains reacted as if they were hearing something totally different from the other types of words and gave a different signal, according to Kuhl, who is a professor of speech and hearing sciences. In addition, brain activity was focused in the temporal lobes of both hemispheres of the brain for each word type.

The children with autism, however, showed no difference in their responses between known and unknown words, meaning they couldnât differentiate between them. However, their brains did react to the backwards words, and the pattern of activity was somewhat similar to that of the typically developing children. Overall brain activity in the children with autism was more diffuse and not focused in the temporal lobes, indicating more of their brains were tied up trying to understand the words.

Earlier work by Kuhl showed dramatic differences in how children 32 to 52 months of age responded to a computer-generated warbling sound and âmotherese,â or baby talk, a speech form that is rich in phonemes. When given a choice by letting them turn their heads in one direction versus the other, normally developing children consistently preferred to listen to motherese, a near universal form of baby talk that is directed at infants and young children. Children with autism preferred the warble sound and chose it consistently.

Youngsters with the most serious symptoms of autism had a stronger preference for the warble than did higher functioning children with autism.

Kuhl believes there is some good news for parents from these studies because there are indications that some autistic children are achieving some learning.

âOne of the puzzles of autism is the variability of children with it,â she said. âWe believe the highest functioning autistic children have some recognition of phonemes (the basic sounds of a language). And this new study shows autistic toddlers can differentiate between backward words, which are not characteristic of a language, and real words. So some learning has gone on.â âTo crack the speech code children must be able to distinguish phonemes, understand known words and be able to decode the word order of a sentence in English or their native language.â

Kuhl said researchers need better measures and tools such as magnetoencephalography, which is a non-invasive technology, to test and look inside the brains of children with autism.

âWeâd like to know what kind of knowledge these children may have locked up in their brains. Children at the high-functioning end of the autism spectrum may have quite a bit. The first possible use of this research would be as a predictor of which children with autism might be responsive to treatment. With these tools we may be able to identify a part of the brain that is not responding, and that may suggest treatments by developing more targeted interventions.â

Babies who don't respond to their names may be at risk for developmental disorders, including autism

Tue, 03 Apr 2007 03:01:14 PST

( from http://www.rxpgnews.com ) Year-old babies who do not respond when their name is called may be more likely to be diagnosed with an autism spectrum disorder or other developmental problem at age 2, making this simple test a potential early indicator for such conditions, according to a report in the April issue of Archives of Pediatrics & Adolescent Medicine, a theme issue on autism spectrum disorders.

Although as many as half of parents of children with autism report concerns about their child's developmental progress before the first birthday, the disorder is usually not diagnosed until age 3 or 4, according to background information in the article. "Earlier identification of autism offers the possibility of early intervention, which holds promise for improving outcomes in children with autism," the authors write. "This has motivated a growing body of research that aims to ascertain the earliest reliable indicators of autism."

Aparna S. Nadig, Ph.D., of the M.I.N.D. Institute, University of California Davis, Sacramento, and colleagues assessed the tendency of infants to respond when their names are called, which is "one of the most consistently documented behaviors in infancy that distinguishes children later diagnosed with autism from those with typical development or developmental delays," they write.

Infants whose older siblings had autism, and who were therefore at risk for autism, were compared with control infants who were not at high risk of developing the disorder. While each child sat at a table playing with a small toy, a researcher walked behind the child and called his or her name in a clear voice. If the child did not respond after 3 seconds, the name was called again up to twice. Fifty-five at-risk infants and 43 control infants completed this test at age 6 months, and 101 at-risk infants and 46 control infants were tested at age 12 months.

"At age 6 months, there was a non-significant trend for control infants to require a fewer number of calls to respond to name than infants at risk for autism," the authors write. "At age 12 months, 100 percent of the infants in the control group 'passed,' responding on the first or second name call, while 86 percent in the at-risk group did."

Forty-six at-risk infants and 25 control infants were followed up for two years; three-fourths of those who did not respond to their name at age 12 months were identified with developmental problems at age 2. A total of 89 percent of infants who did not have an autism spectrum disorder (including autism, Asperger's syndrome and related conditions all defined by deficits in language and social skills) and 94 percent of infants without any developmental delays at two years responded to their name on the first two calls at one year. Of the children who were later diagnosed with autism, half failed the test at one year, and of those who were identified as having any type of developmental delay, 39 percent failed the test.

"Thus, failure to respond to name at the well-child one-year check-up may be a useful indicator of children who would benefit from a more thorough developmental assessment," the authors write. "It will not, however, identify all children at risk for developmental problems."

"Since this task is easy to administer and score and takes few resources, it could be incorporated into well-child pediatric visits at 12 months of age," they conclude. "If a child fails to orient to name, particularly reliably over time, this child has a high likelihood of some type of developmental abnormality and should be referred for more frequent screening, comprehensive assessment and, if indicated, preventive early intervention."

Autism costs society an estimated $3M per patient

Tue, 03 Apr 2007 02:59:15 PST

( from http://www.rxpgnews.com ) Each individual with autism accrues about $3.2 million in costs to society over his or her lifetime, with lost productivity and adult care being the most expensive components, according to a report in the April issue of Archives of Pediatrics & Adolescent Medicine, a theme issue on autism spectrum disorders.

Autism costs society more than $35 billion in direct and indirect expenses each year, according to background information in the article. Relatively little is known about when these costs occur across the lifetime of an individual with autism.

Michael L. Ganz, M.S., Ph.D., Abt Associates Inc., Lexington, Mass., and Harvard School of Public Health, Boston, used data from the medical literature and from national surveys to estimate the direct medical and non-medical costs of autism, including prescription medications, adult care, special education and behavioral therapies. Approximate indirect costs, including lost productivity of both individuals with autism and their parents, were calculated by projecting average earnings and benefits at each age, adjusted for the fact that some autistic individuals can work in supported environments. Only costs directly linked to autism, and no medical or non-medical costs that would be incurred by individuals with or without autism, were included.

These costs were projected across the lifetime of a hypothetical group of individuals born in 2000 and diagnosed with autism in 2003. Costs estimates were broken down into age groups at five-year intervals, with the youngest group age 3 to 7 years and the oldest age 63 to 66 years.

"Direct medical costs are quite high for the first five years of life (average of around $35,000), start to decline substantially by age 8 years (around $6,000) and continue to decline through the end of life to around $1,000," Dr. Ganz writes. "Direct non-medical costs vary around $10,000 to approximately $16,000 during the first 20 years of life, peak in the 23- to 27-year age range (around $27,500) and then steadily decline to the end of life to around $8,000 in the last age group. Indirect costs also display a similar pattern, decreasing from around $43,000 in early life, peaking at ages 23 to 27 years (around $52,000) and declining through the end of life to $0."

Over an individual's life, lost productivity and other indirect costs make up 59.3 percent of total autism-related costs. Direct medical costs comprise 9.7 percent of total costs; the largest medical cost, behavioral therapy, accounts for 6.5 percent of total costs. Non-medical direct costs such as child care and home modifications comprise 31 percent of total lifetime costs.

Because these costs are incurred by different segments of society at different points in an autistic patient's life, a detailed understanding of these expenses could help planners, policymakers and families make decisions about autism care and treatment, Dr. Ganz notes. "Although autism is typically thought of as a disorder of childhood, its costs can be felt well into adulthood," he concludes. "These results may imply that physicians and other care professionals should consider recommending that parents of children with autism seek financial counseling to help plan for the transition into adulthood."

Infants with autistic siblings may display early social, communication problems

Tue, 03 Apr 2007 02:56:54 PST

( from http://www.rxpgnews.com ) Younger siblings of children with autism spectrum disorders do not perform as well on tests of social and communication development compared with siblings of children without developmental problems at ages as young as 12 months, according to a report in the April issue of Archives of Pediatrics & Adolescent Medicine, a theme issue on autism spectrum disorders.

Studies of twins and families indicate that autism and related disorders have a genetic basis, according to background information in the article. This includes milder conditions known as the "broader autism phenotype," consisting of traits that are similar to those associated with autism but are not severe enough to cause disability. Approximately 6 to 9 percent of younger siblings of children with autism spectrum disorders (including autism and related conditions) develop autism spectrum disorders, and others may demonstrate features of the broader autism phenotype.

Wendy L. Stone, Ph.D., and colleagues at Vanderbilt University, Nashville, Tenn., studied 64 younger siblings of children with autism spectrum disorders and 42 younger siblings of children with typical development. The siblings were between the ages of 12 and 23 months (average age 16 months) when they were assessed between 2003 and 2006. Participating children were measured using tests of thinking, learning and memory; an interactive screening tool assessing play, imitation and communication; and a scale rating autism symptoms. Parents were also interviewed and filled out questionnaires regarding their childrenâs social, communication and language skills.

"Younger siblings of children with autism spectrum disorders demonstrated weaker performance in non-verbal problem-solving, directing attention, understanding words, understanding phrases, gesture use and social-communicative interactions with parents, and had increased autism symptoms, relative to control siblings," the authors write. The pattern of scores on tests suggested that a substantial minority of the siblings of autistic children had low scores, as opposed to a few extremely low performers who may have deceptively brought down the average scores. In addition, "the consistency of results obtained across different methods highlights the robustness of these findings."

The weaker performance of siblings of children with autism spectrum disorder may represent early signs of the broader autism phenotype, and highlights the importance of closely monitoring these at-risk children for developmental problems, the authors note. "This research has the potential to increase our knowledge about the early development of autism and to develop tailored intervention and prevention strategies for promoting optimal outcomes in this group of at-risk children," they conclude.

'The eyes have it' -- Autism research yields surprising results

Fri, 30 Mar 2007 02:11:57 PST

( from http://www.rxpgnews.com ) Autistic children are able to interpret the mental state of others by looking at their eyes, contrary to previous research, a new University of Nottingham study has found.

In findings that contradict previous studies, psychologists found that autistic children can 'read' a stranger's mental state based on that person's eyes. Autistic children have long been thought to be poor at interpreting people's mental states based on facial expressions, especially expressions around the eyes.

Some researchers believe that this lack of ability could be central to the social problems experienced by autistic children and adults.

But the latest findings cast doubt on this hypothesis. A study at The University of Nottingham found that autistic children were able to interpret mental states when looking at animated facial expressions. The findings also suggest that the use of moving images, rather than conventional still pictures, gives a much more accurate measure of the abilities of autistic children.

Researchers hope that by increasing understanding of autism, their findings may ultimately help in the teaching and treatment of people with the condition.

Published in the latest issue of the journal Child Development, the study was led by Dr Elisa Back. Her co-researchers were Professor Peter Mitchell and Dr Danielle Ropar of the School of Psychology at The University of Nottingham.

Dr Back said: âPrevious findings show that children and adolescents with autism may have difficulty reading mental states from facial expressions but our results suggest that this is not due to an inability to interpret information from the eyes.

âSurprisingly, autistic children seemed particularly reliant on the eyes and also the mouth when making mentalistic inferences.

âThe conclusions of previous research are largely based on methods that present static photographs to participants. Our study indicates that a more accurate measure of the abilities of those with autism can be obtained through the use of sophisticated digital imaging techniques with animated facial expressions.â

The study compared two groups of autistic children, one group aged 10â14 and one aged 11â15, with two control groups of non-autistic children. They underwent a series of tests to see whether they could gauge the mental state of a stranger by looking at different parts of the face.

Researchers conducted two experiments in which the participants looked at a series of facial expressions on a laptop screen. In the facial images used, the eyes and mouth were either 'freeze-framed' in a neutral expression, or animated and expressive. By showing a sequence of different combinations, they were able to gauge which aspects of the face were used by the autistic children to 'read' someone's mental state â and how successful they were.

In the second experiment, the 18 autistic children involved were as successful as non-autistic children in interpreting mental states, whether they saw the eyes in isolation or in the context of the whole face. This indicates that autistic children do, in fact, make use of information from the eyes â a finding that contradicts prior studies.

An estimated 588,000 people have autism in the UK, according to the National Autistic Society. A mental health survey by the Office for National Statistics found the prevalence of children and young people anywhere on the autistic spectrum is 0.9 per cent â almost one in every 100.

New genetic clues to autism revealed

Sun, 18 Feb 2007 14:23:54 PST

( from http://www.rxpgnews.com )

To amplify the power of possible linkages detected, the researchers analyzed many subsets of data, variously excluding from the sample factors like the submicroscopic anomalies, female sex, and ethnicity. These analyses unmasked several suggestive linkages that would otherwise have eluded detection.

The largest search for autism genes to date, funded in part by the National Institutes of Health (NIH), has implicated components of the brain's glutamate chemical messenger system and a previously overlooked site on chromosome 11. Based on 1,168 families with at least two affected members, the genome scan adds to evidence that tiny, rare variations in genes may heighten risk for autism spectrum disorders (ASD)*.

The study is the first to emerge from the Autism Genome Project (AGP) Consortium, a public-private collaboration involving more than 120 scientists and 50 institutions in l9 countries. Their report is published online in the February 18, 2007 issue of Nature Genetics.

With NIH support, the AGP is pursuing studies to identify specific genes and gene variants that contribute to vulnerability to autism. These include explorations of interactions of genes with other genes and with environmental factors, and laboratory research aimed at understanding how candidate susceptibility genes might work in the brain to produce the disorders.

"This is the most ambitious effort yet to find the locations of genes that may confer vulnerability to autism," said NIH Director Elias A. Zerhouni, M.D. "The AGP is revealing clues that will likely influence the direction of autism research for years to come."

"Although we know autism is highly heritable, complex gene interactions and submicroscopic anomalies create a din of statistical noise that drowns out detection of signals from linked sites in the genome," explained Dr. Bernie Devlin, University of Pittsburgh, who served as a corresponding author on the project along with the University of Toronto's Dr. Stephen Scherer. "To amplify these signals, we brought to bear gene chip technology with a huge sample, and also screened for these fine-level anomalies, factoring them into the analysis."

Clues emerged adding to evidence that implicates components of the brain's glutamate neurotransmitter system in autism. Glutamate increases neuronal activity and plays an important role in wiring up the brain during early development. Since autism likely stems from faulty wiring, a genetic blueprint gone awry in this pivotal neurotransmitter system is a prime suspect. Some key genes associated with the glutamate system are located in chromosome regions previously associated with autism, note the researchers.

Previous studies have also linked abnormal glutamate functioning to disorders such as Fragile X syndrome and tuberous sclerosis, which share some symptoms with autism. It's not unusual for individuals with either syndrome to be diagnosed with autism.

Among the new clues is stronger evidence for an association between autism and sites of genes for neurexins, molecules that build glutamate synapses the connection machinery by which brain cells communicate.

A site on chromosome 11 most strongly linked to autism in this study harbors genes for proteins that shuttle glutamate across the synapse. Although detected previously, the linkage signal at this site was regarded as less important until now.

Submicroscopic anomalies tiny deletions, or the doubling, tripling or even multiplying of stretches of genetic material are relatively common in the human genome and aren't necessarily harmful. However, recent evidence suggests that these anomalies may contribute to risk for or rarely even cause autism if they affect certain sites associated with the disorder. The AGP researchers found a number of these variations in such suspect chromosomal locations in affected individuals, including deletion of a neurexin gene.

These anomalies can also make it more difficult to detect the genes that more commonly account for autism risk, say the researchers. Since each major autism candidate gene likely contributes to risk for a relatively small percentage of families, its linkage signal can easily be lost in the statistical noise generated by those of the anomalies just as a high level of static can drown out a weak radio signal.

To amplify the power of possible linkages detected, the researchers analyzed many subsets of data, variously excluding from the sample factors like the submicroscopic anomalies, female sex, and ethnicity. These analyses unmasked several suggestive linkages that would otherwise have eluded detection.

Researchers last Fall reported (http://www.nimh.nih.gov/press/autismmetgene.cfm ) discovery of a gene version linked to autism and how it likely works at the molecular level to increase risk. The AGP researchers propose that multiple such gene variants, perhaps interacting with each other and with the tiny anomalies, contribute to risk. As more such genes are identified, studies of how they work in the brain in mice and other model systems will help to sort out the genetic and proposed environmental influences on autism spectrum disorders, say researchers.

A second phase of AGP studies will follow up on leads suggested in this first phase.

Autism linked to paternal age

Tue, 05 Sep 2006 18:35:37 PST

( from http://www.rxpgnews.com ) Children of men age 40 and older have a significantly increased risk of having autism spectrum disorders compared with those whose fathers are younger than 30 years, according to an article in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Autism is characterized by social and language abnormalities and repetitive patterns of behavior, according to background information in the article. Autism and related conditions, known collectively as autism spectrum disorders, have become increasingly common, affecting 50 in every 10,000 children as compared with five in 10,000 two decades ago. This increase is partially due to higher levels of awareness and changes in diagnosis processes, but could also reflect an increase in incidence of autism, according to the authors. Older parental age has previously been linked to abnormalities in the brain development of children; however, few studies have effectively examined the effect of mothers' and especially fathers' ages on autism.

Abraham Reichenberg, Ph.D., of the Mount Sinai School of Medicine, New York, and Institute of Psychiatry, King's College London, and colleagues evaluated this association in children born during the 1980s in Israel. All men and three-fourths of the women born in these years were assessed by the draft board at age 17, during which time any psychiatric disorders were recorded. Dr. Reichenberg and colleagues obtained draft board information and the age of the father for 318,506 individuals; age of the mother was available for 132,271 of those.

Two hundred and eight individuals in the larger group (a rate of 6.5 per 10,000) and 110 in the group with both maternal and paternal ages (8.3 per 10,000) had a diagnosis of autism spectrum disorder, according to the information in the draft board registry. Among the paternal age groups of 15 to 29 years, 30 to 39 years, 40 to 49 years and older than 50 years, there were 34 cases, 62 cases, 13 cases and one case, respectively, of autism spectrum disorders. Advancing age among fathers was associated with increased risk of autism. This association persisted after the researchers controlled for year of birth, socioeconomic status and the mother's age, such that the odds of autism spectrum disorder were nearly six times greater among children of men age 40 and older than those of men 29 years and younger. Older age among mothers was not associated with autism after researchers factored in the effect of the father's age.

The authors discuss several possible genetic mechanisms for the paternal age effect, including spontaneous mutations in sperm-producing cells or alterations in genetic "imprinting," which affects gene expression. "It is important to keep in mind, however, that age at paternity is influenced by the sociocultural environment and varies across societies and over time," they continue. "In a given population, a change in the sociocultural environment could produce a change in paternal age at birth. In theory, it could thereby lead to a change in the incidence of genetic causes of autism."

"Although further work is necessary to confirm this interpretation, we believe that our study provides the first convincing evidence that advanced paternal age is a risk factor for autism spectrum disorder," they conclude.

Autism affects functioning of entire brain

Thu, 17 Aug 2006 15:51:37 PST

( from http://www.rxpgnews.com ) A recent study provides evidence that autism affects the functioning of virtually the entire brain, and is not limited to the brain areas involved with social interactions, communication behaviors, and reasoning abilities, as had been previously thought. The study, conducted by scientists in a research network supported by the National Institutes of Health (NIH), found that autism also affects a broad array of skills and abilities, including those involved with sensory perception, movement, and memory.

The findings, appearing in the August Child Neuropsychology, strongly suggest that autism is a disorder in which the various parts of the brain have difficulty working together to accomplish complex tasks.

The study was conducted by researchers in the Collaborative Program of Excellence in Autism (CPEA), a research network funded by two components of the NIH, the National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders.

"These findings suggest that further understanding of autism will likely come not from the study of factors affecting one brain area or system, but from studying factors affecting many systems," said the director of NICHD, Duane Alexander, M.D.

People with autism tend to display 3 characteristic behaviors, which are the basis of the diagnosis of autism, explained the study's senior author, Nancy Minshew, M.D., Professor of Psychiatry and Neurology at the University of Pittsburgh School of Medicine. These behaviors involve difficulty interacting socially, problems with verbal and non-verbal communications, and repetitive behaviors or narrow, obsessive interests. Traditionally, Dr. Minshew said, researchers studying autism have concentrated on these behavioral areas.

Within the last 20 years, however, researchers began studying other aspects of thinking and brain functioning in autism, discovering that people with autism have difficulty in many other areas, including balance, movement, memory, and visual perception skills.

In the current study, Dr. Minshew and her colleagues administered a comprehensive array of neuropsychological tests to a group of children with autism. The researchers tested 56 autistic children, and compared their responses to those of 56 children who did not have autism. The children with autism were classified as having higher functioning autism--an I.Q. of 80 or above, and the ability to speak, read, and write. All of the children in the study ranged in age from 8 to 15 years. The purpose of the test array, Dr. Minshew said, was to determine whether there were any patterns in mental functioning unique to autism.

"We set out to find commonalities across a broad range of measures, so that we could make inferences about what's going on in the brain," Dr. Minshew said.

The researchers found that, across the entire series of tests, the children with autism performed as well as--and in some instances even better than--the other children on measures of basic functioning. Uniformly, however, they had trouble with complex tasks.

For example, regarding visual and spatial skills, the children with autism were very good at finding small objects in a cluttered visual field, on tasks like finding Waldo in the "Where's Waldo" picture books series. However, when asked to perform a complex task, like telling the difference between the faces of similar looking people, they had great difficulty.

Although their memory for the detail in a story was phenomenal, the children with autism had great difficulty comprehending the story. Many were highly proficient at spelling and had a good command of grammar, but had difficulty understanding complex figures of speech, like idioms and metaphors.

"We see this with our patients," Dr. Minshew said. "If you use an expression like 'hop to it,' a child with autism may literally hop."

Other complex tasks were also difficult for them. The children with autism either had poor handwriting, or wrote very slowly. Many had difficulty tying their shoes and with using scissors.

"These findings show that you can't compartmentalize autism under three basic areas," Dr. Minshew said. "It's much more complex than that."

Dr. Minshew explained that the major implication of the finding is that when seeking to understand autism, researchers need to look for a cause or causes that affect multiple brain areas, rather than limiting their search to brain areas dealing with the three characteristic behaviors involving social interactions, communication, and repetitive behaviors or obsessive interests.

"Our paper strongly suggests that autism is not primarily a disorder of social interaction, but a global disorder affecting how the brain processes the information it receives--especially when the information becomes complicated."

In previous research with an imaging technology known as functional magnetic resonance imaging, or fMRI, Dr. Minshew and her coworkers determined that adults with autism have abnormalities in the neurological wiring through which brain areas communicate. In those studies, the researchers found that people with autism had difficulty performing certain complex tasks that involved brain areas working together. (This research is described in previous releases, http://www.nichd.nih.gov/new/releases/final_autism.cfm, and http://www.nichd.nih.gov/new/releases/autism_brain_structure.cfm.)

Dr. Minshew said that such abnormalities in brain circuitry provide the most likely explanation for why the children with autism in the current study have difficulty with complex tasks that require coordination among brain regions but do well on tasks that require only one region of the brain at a time.

The researchers undertook the current study as a follow up to an earlier study they did of adults with autism. The researchers studied children to determine if the features of autism were consistent throughout life, or changed as people with autism grow older. For the most part, the current study revealed that both adults and children with autism experience the same kinds of difficulties with complex tasks.

One difference is that adults with autism appear to score higher on tests involving sensory interpretation than do children with autism. Such tests would involve identifying a number traced on a finger tip, or identifying an object placed in one's hand without looking at it. Dr. Minshew said that as people with autism grow older, they may have less sensory difficulty than they did as children.

Still, adults with autism fare much worse on tests of complex language and reasoning than do other adults. This gap in complex language and reasoning ability between the two groups is not as pronounced when children with autism are compared to other children. This is because children's brains have not yet developed these skills, Dr. Minshew said. However, the gap widens with time. As typical children get older, they develop these higher order language and reasoning skills while adolescents and adults with autism do not.

Autism - the neuroanatomical basis

Thu, 20 Jul 2006 13:17:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of California, Davis, M.I.N.D. Institute have discovered that the brains of males with autism have fewer neurons in the amygdala, a part of the brain involved in emotion and memory. The study, published in the July 19 issue of the Journal of Neuroscience, is the first neuroanatomical study to quantify a key difference in the autistic amygdala.

David Amaral, research director of the UC Davis M.I.N.D. Institute, and former graduate student Cynthia Mills Schumann counted and measured representative samples of neurons in the amygdala of nine postmortem brains of males who had autism and 10 postmortem brains of males who did not have autism. Both subject groups ranged in age from 10-to-44 years at the time of death. Using a technique known as unbiased stereological analysis, Schumann and Amaral counted neurons using a computer-aided microscope system. They found significantly fewer neurons -- cells responsible for creating and transmitting electrical impulses -- in the whole amygdala and its lateral nucleus in the brains of people with autism.

This is the first quantitative evidence of an abnormal number of neurons in the autistic amygdala and the first study to use modern unbiased sampling techniques for autism research, Amaral said.

While we have known that autism is a developmental brain disorder, where, how and when the autistic brain develops abnormally has been a mystery, said Thomas R. Insel, a physician and director of the National Institute of Mental Health . This new finding is important because it demonstrates that the structure of the amygdala is abnormal in autism. Along with other findings on the abnormal function of the amygdala, research is beginning to narrow the search for the brain basis of autism.

Now affecting 1 in every 166 children and primarily affecting males, autism is a lifelong neurodevelopmental disorder characterized by social and communication deficits. While autism has clear behavioral indicators, the neural alterations leading to the deficits have been difficult to pinpoint. In studies dating back to the mid-1980s, researchers began focusing on the amygdala because of its importance in generating appropriate emotional responses and assimilating memories that are key to social learning -- functions that are impaired by autism.

Previous magnetic resonance imaging studies from several laboratories, including the M.I.N.D. Institute, have indicated precocious enlargement of the amygdala in young children with autism, said Schumann, who is now a postdoctoral researcher at the UC San Diego School of Medicine. But these studies were not able to determine whether the number of neurons were different in the autistic amygdala.

Interpreting these earlier qualitative studies was hampered because many postmortem brains available for research were from individuals who had autism as well as epilepsy, a condition known to cause pathology of the amygdala.

Back when these studies were conducted, it wasn't easy to acquire the brain of a deceased person who just had autism, Amaral explained. We are fortunate now to have the Autism Tissue Program, funded by the National Alliance for Autism Research and the National Institutes of Health. With their help, we were able to analyze more than double the number of previously examined postmortem brains, none of which had seizure disorders or any major neurological disorder other than autism.

A better understanding of the neurobiology of the amygdala is crucial to advance autism research, and this study helps answer many important questions about the fundamental basis of autism, said Andy Shih, chief science officer for the National Alliance for Autism Research, which is now merged with Autism Speaks. Autism Speaks and the Autism Tissue Program were proud to support this project so that these important discoveries could be made.

By counting the actual number of neurons in tissue samples, the researchers also overcame a methodological concern raised by studies that described changes in neuronal density, or neurons per unit volume, in portions of the amygdala.

Differences in neuron density could just indicate changes in tissue volume rather than changes in total cell number. The only way to determine the actual difference is to systematically count samples of neurons in a defined volume, Amaral said.

With this latest confirmation that the amygdala is pathological in autism, Amaral and colleagues will now determine why there are fewer neurons in the amygdala and if other parts of the brain are similarly affected.

We need to look at other brain regions to find out if the cell loss is idiosyncratic to the amygdala or a more general phenomenon, he said. We're in the very early stages of understanding autism and its neurological pathologies. It's clearly a process with many steps, and at least we are now one step further.

Additional research will also help identify the developmental point in time at which the neuron reduction actually occurs, which the current study does not address.

One possibility is that there are always fewer neurons in the amygdala of people with autism. Another possibility is that a degenerative process occurs later in life and leads to neuron loss. More studies are needed to refine our findings, said Schumann.

Trophoblast inclusions in placenta may be the earliest marker for autism

Tue, 27 Jun 2006 03:15:37 PST

( from http://www.rxpgnews.com ) Researchers at Yale School of Medicine have discovered in the placenta what may be the earliest marker for autism, possibly helping physicians diagnose the condition at birth, rather than the standard age of two or older.

The findings are reported in the June 26 online issue of Biological Psychiatry. Autism is a developmental disorder that has a profound effect on socialization, communication, learning and other behaviors. In most cases, onset is early in infancy. Information on the earliest development aspects of autism in children has been limited even though approximately one in every 200 children is diagnosed with an Autism Spectrum Disorder (ASD). The earlier the diagnosis is made, the greater the treatment impact.

Current studies are searching for characteristics in children at risk for ASD so that the diagnosis can be made prior to age one. The ideal time for diagnosis would be at birth, according to senior author on the study Harvey J. Kliman, M.D., research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at the Yale School of Medicine.

In previous work, Kliman had observed an unusual pathologic finding in the placentas from children with Asperger Syndrome, an ASD condition which, like autism, impairs the ability to relate to others.

"By serendipity, at a dinner party I happened to sit next to George M. Anderson, a research scientist in the Yale Child Study Center who had access to many cases of children with ASD," said Kliman. "We realized that by working together we might be able to determine if this placental abnormality could be a useful clinical marker."

With the help of Andrea Jacobs-Stannard, a student in Kliman's laboratory, and Katarzyna Chawarska and Fred R. Volkmar of the Yale Child Study Center, the group designed a study to see if the placental abnormality, specifically the presence of trophoblast inclusions, was a marker for ASD. The multidisciplinary team of Yale researchers compared placentas from 13 children with ASD to those from 61 unaffected children for the presence of trophoblast inclusions.

They found that the placentas from ASD children were three times more likely to have the inclusions. Kliman and the team identified trophoblast inclusions by performing microscopic examinations of placental tissues.

"We knew that trophoblast inclusions were increased in cases of chromosome abnormalities and genetic diseases, but we had no idea whether they would be significantly increased in cases of ASD," said Kliman. "These results are consistent with studies by others who have shown that ASD has a clear genetic basis."

Trophoblast inclusions reflect abnormal folding of microscopic layers in the placenta and appear to result from altered cell growth. Kliman likened the presence of trophoblast inclusions to an automobile check-engine-light. "When the light goes on it simply means that something is not right," said Kliman. "If the light is on and there is, for example, steam coming from under the hood, then it is likely that the radiator is leaking. However, if the check engine light is on and there is nothing obviously wrong, then the car should be carefully checked."

The Yale team plans to replicate the evaluation with larger multi-center and prospective studies. They will examine the placentas of the children in the study in greater detail to gain insight into the biological basis of the inclusions in ASD.

Volkmar said, "If the work is confirmed by the next series of studies, then the finding of trophoblast inclusions at the time of birth in the absence of any obvious genetic abnormalities would be an indication to have a child examined by a specialist to determine the presence of ASD."

Pediatricians fail to screen for autism

Wed, 10 May 2006 12:58:37 PST

( from http://www.rxpgnews.com ) Few Maryland and Delaware primary care pediatricians screen patients regularly for autism and autism-spectrum disorders (ASD) as part of their overall look at possible developmental delays, according to results of a joint study from Johns Hopkins Children's Center and the Johns Hopkins Bloomberg School of Public Health.

Of the 255 pediatricians who participated in the study, 209 (82 percent) said they regularly screen their patients for general developmental delays, but only 20 of the 255 (8 percent) said they do so for ASD. Of those who do not screen routinely for ASD, almost two-thirds (62 percent) said they failed to do so because they weren't familiar with the screening tools.

"Lack of familiarity with ASD screening tools appears to be the single greatest barrier to routine screening," said Susan dosReis, Ph.D., of the Children's Center Division of Child and Adolescent Psychiatry and lead author of the paper, which appears in a May 11 supplement of the April issue of the Journal of Developmental and Behavioral Pediatrics.

The findings suggest that screening for ASD remains largely opportunistic rather than systematic, researchers say.

Screening is essential, as delay in diagnosis and treatment generally leads to poorer outcomes in children with developmental disorders.

"This study suggests that current national efforts may not be sufficient to actively promote the use of ASD screening tools in the general pediatric practice," dosReis added. "So it is important to learn what some obstacles might be and what needs to be done to overcome those barriers."

Previous research suggests that another factor might be that many pediatricians do not feel well-trained in general developmental and behavioral issues, researchers say.

Enhancement of residency training, complemented by introduction and training in ASD screening tools, might boost ASD screening in the general pediatric practice, dosReis added.

Almost half (47 percent) of the physicians who did not screen routinely said they preferred to send the child to a clinical specialist, whereas nearly one-third (32 percent) cited lack of time as a major reason for not screening. Of those who reported screening regularly for ASD, 90 percent said they were usually prompted to do so by parental concern and/or suspicion of ASD during routine examination.

Of the 18 percent who reported not screening routinely for any developmental delays, 73 percent cited lack of time as their top reason.

The prevalence of autism, estimated to be between 12 and 40 cases per 10,000 children, has grown over the last decade. The reasons behind the higher prevalence have flamed an ongoing debate. Some researchers attribute the increase to an actual jump in the incidence of the disorder, while others claim it is because of more aggressive screening and new diagnostic criteria, which leads to a higher number of new diagnoses.

In the Hopkins study, 99 percent of the pediatricians who believed there is an increase in ASD prevalence attributed it, at least in part, to new diagnostic criteria. At the same time, 38 percent said that underlying risk factors, other than new diagnostic guidelines, have played a role. Of these, one-third believed that environmental factors played a role, while only 7 percent attributed the increase to genetic factors, and 1 percent attributed it to vaccinations.

Researchers caution that the findings cannot be generalized beyond Maryland and Delaware because screening practices might vary by geographic area.

Why some people lack social skills

Mon, 10 Apr 2006 14:05:37 PST

( from http://www.rxpgnews.com ) Poor social skills in some people may be due to their inability to process faces, says a new study.

Known as autism spectrum disorder (ASD), it is characterised by varying degrees of impairment in communication skills, social interaction and restricted, repetitive and stereotyped patterns of behaviour.

It had been thought that lack of social skills was due to abnormalities in particular brain areas. But University of London researchers compared the brain scans of 32 people and found that ASD is a problem in the part of the brain that processes faces, reported online edition of BBC News.

The face processing areas of people suffering from the disorder are not well connected to those parts of the brain that control attention, it said.

The researchers took the brain scans of 16 people with ASD and above-average IQs, as well as those of 16 unaffected volunteers. They were shown four images on the screen - two of houses and two of faces.

Scans showed there were marked differences in the brain activity of the two groups, the study appeared in the journal Neuroimage said.

In the unaffected group, paying attention to pictures of faces caused a significant increase in brain activity. But for people with ASD, paying attention to faces made no impact at all on the brain.

"We know that many people with ASD have particular difficulties in this area and we are hopeful that an improved understanding of these processes will enable people to receive appropriate and helpful support," said Richard Mills, director of research for the National Autism Society.

ASD can often be reliably detected by the age of three years, and in some cases as early as 18 months.

The role of evolutionary genomics in the development of autism

Wed, 22 Mar 2006 01:47:37 PST

( from http://www.rxpgnews.com ) Scientists at the London School of Economics, UK and Simon Fraser University, Canada have described the first hypothesis grounded in evolutionary genomics explaining the development of autism.

In an article to be published in a forthcoming issue of Journal of Evolutionary Biology, Dr Christopher Badcock and Professor Bernard Crespi explore the 'imprinted brain hypothesis' to explain the cause and effect of autism and autistic syndromes such as Asperger's syndrome, highlighted by the book The Curious Incident of the Dog in the Night-Time, which involves selective disruption of social behaviour that makes individuals more self-focussed whilst enhancing skills related to mechanistic cognition.

The 'imprinted brain hypothesis' suggests that competition between maternally and paternally expressed genes leads to conflicts within the autistic individual which could result in an imbalance in the brain's development. This is supported by the fact that there is known to be a strong genomic imprinting component to the genetic and developmental mechanisms of autism and autistic syndromes.

Professor Bernard Crespi from Simon Fraser University, Canada explains: "The imprinted brain hypothesis underscores the viewpoint that the autism spectrum represents human cognitive diversity rather than simply disorder or disability. Indeed, individuals at the highest-functioning end of this spectrum may have driven the development of science, engineering and the arts through mechanistic brilliance coupled with perseverant obsession."

The core behavioural features of autism such as self-focussed behaviour, altered social interactions and language and enhanced spatial and mechanistic cognition and abilities as well as the degree to which the brain functions and structures are altered also supports this hypothesis.

State-of-the-art eye tracking system to help understand autistic children

Tue, 21 Mar 2006 02:19:37 PST

( from http://www.rxpgnews.com ) Using new technology and a unique approach, Binghamton University researchers are hoping to help children with autism spectrum disorders (ASD) deal with their most common and problematic areas of deficit - social and life skills.
Raymond Romancyzk, director of Binghamton University's Institute for Child Development, is heading up an intensive research project to learn how children - with and without autism - interact with the world around them. Using a combination of a state-of-the-art eye tracking system, miniaturized psychophysiological monitoring and multiple computers for high-speed processing, Romancyzk and his team are able to ask questions that could help answer how individuals with autism process information and stimuli from the world around them.

The team is using a tracking system that doesn't require the subject to wear a tracking device. Instead a video camera, built into a small desk observes a child. First, reference points are established by having the child watch a short animation, and with the help of a computer, the system overlays the position of a child's eyes onto a second video image of the child's field of vision. While the tracking systems observes the child's face, the eyes are located in the video image and computers record further eye movement.

This allows the team to see where and for exactly how long and where the child is looking, such as at faces, objects, and actions, either live or on video, and permits measurement of an index of physiological anxiety, and the more standard measurement of affect, performance, and behavior. The fact that children don't have any physical contact with the eye tracking system and don't have to wear any special apparatus makes it a great tool even with very young children, whether they have autism or not.

Gathering data from "typical' children will help researchers better distinguish where the differences between non-autistic children and children with autism. The new technology is enabling researchers to ask questions that may have far-reaching implications for educational and clinical approaches for autism.

"Part of the reason for this elaborate scheme is we've also been doing some research on how adults interact with children with autism, how they perceive what they think is going on versus what the child is actually doing," said Romanczyk. "This ties into the subtleties of social interaction that we take for granted. You look at someone and you can tell by their body posture, their gestures, tone of voice, eye gaze and so on, what's being communicated. With children with autism, it's more difficult to do."

Innovative approach affords clearer view of autism

Tue, 21 Mar 2006 02:15:37 PST

( from http://www.rxpgnews.com ) Using new technology and a unique approach, Binghamton University researchers are hoping to help children with autism spectrum disorders (ASD) deal with their most common and problematic areas of deficit - social and life skills.

Raymond Romancyzk, director of Binghamton University's Institute for Child Development, is heading up an intensive research project to learn how children - with and without autism - interact with the world around them. Using a combination of a state-of-the-art eye tracking system, miniaturized psychophysiological monitoring and multiple computers for high-speed processing, Romancyzk and his team are able to ask questions that could help answer how individuals with autism process information and stimuli from the world around them.

The team is using a tracking system that doesn't require the subject to wear a tracking device. Instead a video camera, built into a small desk observes a child. First, reference points are established by having the child watch a short animation, and with the help of a computer, the system overlays the position of a child's eyes onto a second video image of the child's field of vision. While the tracking systems observes the child's face, the eyes are located in the video image and computers record further eye movement.

This allows the team to see where and for exactly how long and where the child is looking, such as at faces, objects, and actions, either live or on video, and permits measurement of an index of physiological anxiety, and the more standard measurement of affect, performance, and behavior. The fact that children don't have any physical contact with the eye tracking system and don't have to wear any special apparatus makes it a great tool even with very young children, whether they have autism or not.

Gathering data from "typical' children will help researchers better distinguish where the differences between non-autistic children and children with autism. The new technology is enabling researchers to ask questions that may have far-reaching implications for educational and clinical approaches for autism.

"Part of the reason for this elaborate scheme is we've also been doing some research on how adults interact with children with autism, how they perceive what they think is going on versus what the child is actually doing," said Romanczyk. "This ties into the subtleties of social interaction that we take for granted. You look at someone and you can tell by their body posture, their gestures, tone of voice, eye gaze and so on, what's being communicated. With children with autism, it's more difficult to do."

Autism Phenome Project aims to redefine autism by identifying distinct subtypes

Fri, 10 Mar 2006 21:29:37 PST

( from http://www.rxpgnews.com ) Multidisciplinary teams of physicians and scientists at the University of California, Davis, M.I.N.D. Institute have launched the nation's most comprehensive assessment of children with autism to detect the biological and behavioral patterns that define subtypes of the disorder.

Called the Autism Phenome Project, the large-scale, longitudinal study will enroll 1,800 children 900 with autism, 450 with developmental delay and 450 who are typically developing who will undergo a thorough medical evaluation in addition to systematic analyses of their immune systems, brain structures and functions, genetics, environmental exposures and blood proteins. Children will be 2 to 4 years old when they begin participating in the study, and their development will continue to be evaluated over the course of several years. The first phase of the research is funded by the UC Davis M.I.N.D. Institute and philanthropic donations.

Children with autism clearly are not all the same, said David G. Amaral, research director of the UC Davis M.I.N.D. Institute and co-director of the project. The tremendous variation leads us to believe that autism is a group of disorders rather than a single disorder several autisms versus one autism. We are determined to provide the specific biomedical and behavioral criteria that accurately define distinct subtypes.

Autism has common hallmarks: difficulties initiating and sustaining social interactions, impaired communication skills and restricted, repetitive patterns of behavior. However, these hallmarks vary in severity. In addition, some children with autism can have co-existing conditions such as cognitive impairments, seizures, coordination issues or gastrointestinal difficulties, while others do not. This heterogeneity has been a major obstacle to progress in autism science.

Another obstacle involves access to reliable data. Autism science includes many quality studies on specific aspects of the disorder from genetics and immunology to behavior and imaging that can be difficult to combine and compare. With the Autism Phenome Project, UC Davis M.I.N.D. Institute researchers aim to overcome this limitation.

We spent two years designing the project so that it would be both comprehensive in scope and fully capable of integrating data across disciplines, said Amaral, a neuroscientist who specializes in brain systems involved in memory, emotion and social behavior. Our goal is to identify specific types of autism and develop a database of biomedical information that can be shared with the worldwide community of autism scientists. This is crucial to refining our understanding of autism and to developing targeted treatments for a specific 'type' of autism as early as possible so children can reach their fullest potential.

According to Thomas R. Insel, a physician who is director of the National Institute of Mental Health, the Autism Phenome Project is an important new direction in autism research. Multifaceted biomedical approaches are exactly what is needed right now, said Insel. This is a monumental task, but one that needs to be undertaken if we are to accurately diagnose and treat people with autism.

While the Autism Phenome Project is ambitious, Amaral believes its successful completion will shorten by decades the road to discovering the causes and treatments of autism, a neurodevelopmental disorder that now affects 1 in 166 children in the United States. The unexplained rise in autism prevalence has frustrated parents and scientists trying to find answers.

The extraordinary biomedical tools currently available at the M.I.N.D. Institute make it the ideal environment for launching this clinical research effort, he said. The time is right for us to build a strong database of information that we can all share in order to speed the discovery process and clarify the variability that now plagues autism research. From there, we can more quickly identify causes and treatments, and by adding collaborative partners we will be able to gather as much information as quickly as possible.

Brain Enlargement May Be Characteristic Of Autism

Thu, 08 Dec 2005 15:19:38 PST

( from http://www.rxpgnews.com ) Magnetic resonance imaging (MRI) has found evidence of brain enlargement in a relatively large sample of children with autism, compared with children who do not have the disorder, according to a study in the December issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Autism is a complex neurodevelopmental disorder defined by social deficits, abnormalities in communication, and stereotyped, repetitive behaviors. While the neuroanatomical basis of this condition is not yet known, numerous lines of evidence suggest that abnormalities in brain volume may be characteristic of autism, according to background information in the article.

Heather Cody Hazlett, Ph.D., of the University of North Carolina, Chapel Hill, and colleagues examined brain volume and head circumference (HC) in children with and without autism. They analyzed data from an ongoing MRI study on 51 children with autism aged 18 to 35 months and a comparison group made up of 25 children without autism (14 with typical development, and 11 with developmental delay without evidence of a pervasive developmental disorder). Retrospective longitudinal HC measurements were also gathered from medical records on a larger sample of 113 children with autism and 189 control children, from birth to age three years.

Significant enlargement was detected in cerebral cortical volumes but not cerebellar volumes in individuals with autism, the authors report. Enlargement was present in both white and gray matter, and it was generalized throughout the cerebral cortex.

The cerebral cortex of the brain is responsible for the processes of thought, perception, and memory, among other functions. The cerebellum is a structure that controls complex motor functions. Gray matter (GM) represents information processing centers in the brain, while white matter (WM) represents connections between those processing centers.

[In children with autism] head circumference appears normal at birth, with a significantly increased rate of HC growth appearing to begin around 12 months of age, the authors write.

The findings from this study confirm the presence of generalized cerebral cortical GM and WM brain volume enlargement at age two in individuals with autism, they conclude. Given the strong relationship between HC and brain volume, the onset of this enlargement appears likely to be during the postnatal period and may begin as late as the latter part of the first year of life.

Findings pinpoint mechanism behind social deficits in autism

Mon, 05 Dec 2005 04:19:38 PST

( from http://www.rxpgnews.com ) New imaging research at UCLA detailed Dec. 4 as an advance online publication of the journal Nature Neuroscience shows children with autism have virtually no activity in a key part of the brain's mirror neuron system while imitating and observing emotions.

Mirror neurons fire when a person performs a goal-directed action and while he or she observes the same action performed by others. Neuroscientists believe this observation-execution matching system provides a neural mechanism by which others' actions, intentions and emotions can be understood automatically.

Symptoms of autism include difficulties with social interaction -- including verbal and nonverbal communication -- imitation and empathy. The new findings dramatically bolster a growing body of evidence pointing to a breakdown of the brain's mirror neuron system as the mechanism behind these autism symptoms.

"Our findings suggest that a dysfunctional mirror neuron system may underlie the social deficits observed in autism," said Mirella Dapretto, lead author and assistant professor in residence of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA and the David Geffen School of Medicine at UCLA. "Together with other recent data, our results provide strong support for a mirror neuron theory of autism. This is exciting because we finally have an account that can explain all core symptoms of this disorder."

Conducted at the Semel Institute's Ahmanson-Lovelace Brain Mapping Center, the research used functional magnetic resonance imaging (fMRI) to measure brain activity in 10 high-functioning children with autism while they imitated and observed 80 photos depicting different emotions such as anger, fear, happiness or sadness. In addition, the brain activity of 10 typically developing children was studied while performing the same tasks.

Separately, symptom severity of each child with autism was tested using two independent measures (the Autism Diagnostic Observation Schedule -- Generic, and the Autism Diagnostic Interview).

The study shows that unlike typically developing children, children with autism have virtually no activity in the pars opercularis of the inferior frontal gyrus, identified by previous research as a key part of the mirror neuron system. Importantly, the level of mirror neuron activity seen in children with autism was inversely related to symptom severity in the social domain.

Children with autism also showed reduced activity in the emotion centers of the brain, consistent with the hypothesis that this mirroring mechanism may play a crucial role for understanding how others feel and for empathizing with them.

All of the children rehearsed the tasks prior to the fMRI scans to assure researchers they could perform the tasks. Both groups performed equally well. Normal brain activity in areas of the brain involving sight and facial movements indicated that the children with autism remained on task during the fMRI scans.

Methylphenidate Shows Promise In The Treatment Of Hyperactivity Associated With Autism-Spectrum Disorders

Tue, 08 Nov 2005 17:36:38 PST

( from http://www.rxpgnews.com ) Medication commonly used to treat attention-deficit hyperactivity disorder (ADHD) may be effective for treatment of hyperactivity symptoms in children with autism and related pervasive developmental disorders, according to a study in the November issue of Archives of General Psychiatry, one of the Archives of General Psychiatry, one of the JAMA/Archives journals.

Children with autism and other pervasive developmental disorders often also have symptoms of hyperactivity, distractibility and impulsiveness requiring treatment, according to background information in the article. Some previous small studies on the use of medications to treat hyperactivity in these children have shown promise, although side effects have been common, including irritability and social withdrawal.

David J. Posey, M.D., Indiana University School of Medicine, Indianapolis, and colleagues in the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network conducted this study. The RUPP Autism Network is funded by the National Institute of Mental Health and is dedicated to the development and testing of treatments for children with autism and related conditions. In this study the investigators conducted a randomized, placebo-controlled crossover trial to determine whether methylphenidate (a medication commonly used in the treatment of ADHD) would be effective in reducing hyperactivity and impulsiveness in children with pervasive developmental disorders. The trial included a one-week phase to test whether the participants could tolerate three different dose levels of the medication. This was followed by a four-week (crossover) phase during which the children were given one of three doses of methylphenidate or placebo in random order to assess effectiveness. Children showing a positive response were treated for an additional eight-week period to ensure that gains were stable. Response to treatment was assessed by parents and teachers using standardized ratings of behavior.

Seventy-two children, aged five to 14 years participated in the study. Six participants (eight percent) had intolerable negative side effects with more than one dosage level and withdrew from the study. Sixteen of the remaining children had intolerable negative side effects at the highest dose and were randomized to a modified crossover phase that omitted the highest dose. Seven participants withdrew due to intolerable negative side effects during the crossover phase, three at the highest dose, three at the medium dose and one while receiving the lowest dose. One child withdrew from the study for unspecified reasons, 58 children completed the crossover phase of the study.

Forty-four (76 percent) of the 58 participants responded during at least one of the four treatment conditions, the researchers report. Methylphenidate was consistently more effective in improving inattention, distractibility, hyperactivity and impulsivity than placebo.

"At present, methylphenidate is a reasonable choice to target hyperactivity in the context of PDDs [pervasive developmental disorders], given modest group effects and a response rate that approaches 50 percent," the authors conclude. "However, caregivers should be cautioned about the strong possibility of adverse effects. In addition, practitioners should be prepared to suspend treatment if considerable adverse effects are reported. Further secondary analyses are planned to better delineate individual responses and other moderators of response, including genotype."

TEDS - Main autism behaviour types are not genetically linked

Tue, 06 Sep 2005 01:37:38 PST

( from http://www.rxpgnews.com ) Scientists at the MRC Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry, King's College London, have discovered that two sets of behaviours that co-occur in autism spectrum conditions appear to be caused by different sets of genes.

The report by Dr Angelica Ronald in collaboration with Professor Robert Plomin and Dr Francesca Happé - published in Developmental Science - could help advance future diagnosis, treatment and understanding of autism spectrum conditions.

In an autism diagnosis, two types of behaviours must be displayed; those that reflect social impairment such as a difficulty in making friends and non-social obsessive and repetitive behaviours such as sticking to rigid routines. These two types of symptoms can both have massive impact on children's development. The researchers were motivated to investigate these two components separately because they represent two very different types of behaviours and it is not clear why they co-occur in autism spectrum conditions.

The study collected data from the UK-based Twins Early Development Study (TEDS) through parent and teacher reports on 3000 pairs of seven-year-old twins. Participants completed a questionnaire designed to assess social and non-social behaviours that are characteristic of autism spectrum conditions but also seen in the general population. The questions assessed the extent to which the twins displayed a range of behaviours, such as how considerate of other people's feelings they are or whether they are fussy and over-particular.

The researchers found that identical twins (where each twin shares the same set of genes) tended to show similar levels of social impairments to each other: i.e. both twins would show either many or few social impairments. In contrast, fraternal twins (where only a proportion of their genes are shared) often had very different levels of social impairments to each other. The same pattern of results was found in the twins for non-social behaviours. This demonstrated that both social and non-social behaviours are highly heritable, that is, a large proportion of the variation of these types of behaviours in the general population is due to genetic influences.

The researchers then posed themselves a new question: whether social and non-social behaviours are influenced by the same set of genes. If the same genes operate on both, one would expect high correlations between social impairments in one twin and non-social behaviours in the other twin in identical twin pairs. Lower correlations would be expected in fraternal twins because they do not share all their genes.

The researchers did not find evidence to suggest that the same genes are involved. They found that social and non-social impairments did not correlate very highly and in many cases, for example, if one identical twin showed social impairments, their co-twin did not show any non-social impairments. The results of this study indicated that most of the genes influencing social impairments are different to those that influence non-social behaviours.

Dr Angelica Ronald said: "This study suggests for the first time that social and non-social behaviours, which are both shown in autism spectrum conditions, are caused by mainly different sets of genes. It suggests that 'genes for autism' is a misnomer: there are several genetically distinct components involved. This finding has important implications for DNA and brain studies: it may be better to study the social and non-social components separately rather than requiring that a child has both components, which is what traditional diagnosis requires."

Telephone assessments with A-TAC can identify childhood autistic disorders

Fri, 02 Sep 2005 02:27:38 PST

( from http://www.rxpgnews.com ) A telephone interview with parents devised by psychiatrists can be used successfully for assessing autistic spectrum disorders in their children.

These disorders include tics, attention-deficit hyperactivity disorder (ADHD) and other psychiatric problems, such as developmental co-ordination disorder and specific learning disorders.

This Swedish study, published in the September issue of the British Journal of Psychiatry, set out to test a parent telephone interview focused on autistic disorders. The Autism-Tics, ADHD and Other Comorbidities Inventory (A-TAC) is a comprehensive screening interview developed at Goteborg University to screen general populations in research and mental health surveys. It is intended for use with parents and lay people, rather than expert interviewers.

The parents of 84 children in contact with a child neuropsychiatric clinic, and 27 healthy control children, were interviewed over the telephone using the A-TAC, which takes between 15 and 35 minutes to complete. The validity and reliability of the test was assessed.

Test reliability was found to be excellent overall. It was highly significant for all the dimensions assessed, and good for most aspects of the neuropsychiatric disorders, particularly for autistic spectrum disorder, tics, ADHD, learning disorders and developmental co-ordination disorder.

The researchers commented that the A-TAC compared very well with an entirely different diagnostic procedure - a comprehensive neuropsychiatric assessment by a team of clinical specialists.

They are now developing A-TAC further, by including more questions. This new test will be further validated in other neuropsychiatric patient groups, in child and adolescent psychiatry, and in the general population.

Protein Snapin as a potential drug target in Autism

Thu, 25 Aug 2005 06:39:38 PST

( from http://www.rxpgnews.com ) Rutgers' Bonnie Firestein likens nerve cells to trees -- some are short and bushy with many branches while others are tall with a few branches coming out of one or two main trunks. Different branching patterns correlate with specific disorders and Firestein's quest is to discover how these dissimilar patterns come about and why.

A new paper by Firestein and her colleagues at Rutgers, The State University of New Jersey, examines the role of the protein snapin in nerve branch, or dendrite, patterning and its potential as a drug target in therapies aimed at learning and memory disorders. The article will appear in the journal Molecular Biology of the Cell but appeared online today at MBC in Press (www.molbiolcell.org/in_press.shtml).

While disorders like autism may arise from a multiplicity of causes, research at the cellular level, such as that of Firestein and her Rutgers team, is creating an important point of entry for early intervention with therapeutic drugs.

Dendrites are the input centers of neurons -- where nerve cells receive information that they pass on to another nerve cell or to the brain. When there is an abnormal decrease in dendrite branches, there are fewer sites to receive information and communication may be impeded. Individuals with disorders such as autism and Rett syndrome display not only fewer branches, but also show two quite different dendrite patterns. Firestein's most recent work explores the how and why of dendrite branching and patterning.

"It's not just how many branches there are, but where they are and the pattern they form," said Firestein, an assistant professor in Rutgers' department of cell biology and neuroscience. "The patterning actually affects the way a cell signals and understanding the patterning could be just as important as understanding how many branches are there. Ultimately, this could lead to new drugs designed to modulate the patterning activity."

Firestein has worked extensively with cypin, a protein that regulates dendrite numbers (a news release is posted online at ur.rutgers.edu/medrel/viewArticle.html?ArticleID=3708). Cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton. Now Firestein's research group has turned its attention to the protein snapin. When snapin binds to cypin, tubulin is crowded out, so fewer dendrites assemble and more branching occurs.

When researchers overexpressed snapin in hippocampal neurons in the lab, the number of primary dendrites growing out of the cell body decreased, but many more secondary dendrites branched off them.

"This is significant not just in identifying snapin as a protein that shapes the dendrites, but also in pinpointing a drug target where one can regulate the interaction of snapin with cypin," Firestein explained.

Both of these proteins have many other functions in the nerve cell environment and elsewhere in the body. "We need to change cypin's function for branching but not its other functions," Firestein said. "Rather than a drug that blocks cypin, we need a drug that affects the binding between the cypin and snapin. This is easier to design and cypin can still function with the other proteins it binds to."

Firestein's goal is to build "a core pathway of dendric branching" a sequence of steps, each affecting the next, with cypin at the center. "Our pathway says cypin does this; now what regulates cypin? Here snapin has a role. And what does snapin regulate?" said Firestein. "Our hope is in ten years, we will have a whole pathway mapped out so that we can target different points in the pathway with new drugs."

Two chromosomes linked to susceptibility for type of autism

Wed, 08 Jun 2005 13:42:38 PST

( from http://www.rxpgnews.com ) A new Cincinnati Children's Hospital Medical Center study links regions of two chromosomes to susceptibility for a type of autism characterized by regression in development. Developmental regression can include the loss of previously acquired language, social skills or both.

Moreover, the study is the first to identify involvement of chromosome 21 in this type of autism. This may explain the increased prevalence of autism spectrum disorders (ASD) among children with Down syndrome, who have an extra copy of chromosome 21 and are 10 times more likely to have an ASD than the general population.

The findings represent "the important first step in identifying genetic variants that may contribute to susceptibility to this specific type of ASD," says Cindy Molloy, M.D., lead author of the study. Dr. Molloy is a physician at Cincinnati Children's in the Center for Epidemiology and Biostatistics and in the division of developmental disabilities.

The study is published in the online edition of the journal Molecular Psychiatry.

Dr. Molloy and colleagues in the division of human genetics examined a national database and DNA bank of hundreds of families with ASD. They identified 32 pairs of siblings, one trio of siblings and one pair of cousins who showed definite evidence of regression at the age of approximately 18 to 24 months. They confirmed previous evidence for linkage with ASD on chromosome 7 and found new evidence for susceptibility on chromosome 21 in this subset of ASD families. The research team is now sequencing genes in those regions to find the specific genetic variant that either contributes to susceptibility or modifies the disease.

"Among children with autism or ASD, 20 to 30 percent have a history of regression," says Dr. Molloy. "We think this represents a genetically distinct subgroup."

The Autism Society of Greater Cincinnati has just awarded Dr. Molloy a $40,000 grant to continue this research and extend it to families in the Cincinnati area.

Autism is a complex developmental disability that affects an individual in the areas of social interaction and communication. Autism is a spectrum disorder that affects each individual differently and to varying degrees of severity. As many as 1.5 million Americans - children and adults - are thought to have autism today, according to the Autism Society of America.

Autism Gene Pinpointed on Chromosome 17

Fri, 06 May 2005 16:08:38 PST

( from http://www.rxpgnews.com ) Autism is a complex disease caused by the interaction of multiple genes and environmental influences. As a result, scientists' previous attempts to locate a genetic risk factor have proved inconclusive. No researchers have been able to pinpoint a predisposing gene and then duplicate their efforts a key piece of proof required for scientific validity.

For the first time, a team of UCLA geneticists have isolated the likely region of an autism gene on chromosome 17 and then successfully duplicated their efforts in a separate population. In an earlier discovery, the scientists were surprised to find that the gene contributes to autism only in boys, perhaps explaining why girls have a dramatically lower risk of developing the disease.

After twice linking the risk gene to band 17Q21, the UCLA team is now conducting DNA testing to identify the precise site on the chromosome, which will bring them closer to finding the gene mutation. This is the first step to providing better screening and potential treatments for autism.

AUTHORS
Dr. Dan Geschwind, associate professor of neurology; Rita Cantor, adjunct professor of human genetics; Stan Nelson, professor of human genetics; Jennifer Stone, graduate student researcher, at the David Geffen School of Medicine at UCLA.

Specific Behaviors In Infants Can Predict Autism

Fri, 06 May 2005 16:06:38 PST

( from http://www.rxpgnews.com ) Canadian researchers have become the first to pinpoint specific behavioral signs in infants as young as 12 months that can predict, with remarkable accuracy, whether a child will develop autism.

The preliminary findings, published this month in the International Journal of Developmental Neuroscience, were taken from an ongoing study of 200 Canadian infants, the largest study of its kind in the world. The infants, many of whom have been followed from birth to 24 months, are younger siblings of children who have been diagnosed with autism.

Studies show that families with one autistic child have a roughly five to10 percent chance of a second child being diagnosed with autism, a rate of recurrence about 50 times higher than the general population.

The Canadian study, which began as a collaboration of McMaster University's

Offord Centre for Child Studies in Hamilton, The Hospital for Sick Children in Toronto and the IWK Health Centre in Halifax, has gained international attention. Initially funded by The Hospital for Sick Children Foundation, and currently by the Canadian Institutes of Health Research (CIHR), it has mushroomed into a global initiative involving leading autism researchers in 14 cities across Canada and the U.S.

Chaired by Lonnie Zwaigenbaum, a developmental pediatrician with the Offord Centre and McMaster Children's Hospital and a lead investigator for the Canadian study, the Canada - U.S. Baby Sibs Research Consortium is supported by the National Alliance for Autism Research (NAAR) and the National Institute of Child Health and Human Development (NICHD) in the U.S. It is widely regarded as one the most exciting developments in autism research today.

"This is groundbreaking work that is pushing the frontier of what we know about the biological nature of autism, and why it emerges so early in life," says Dr. Zwaigenbaum. "Our hope is that it will lead to the development of new and earlier treatments that could make a huge difference for these children."

Second only to mental retardation as the most common developmental disability, autism forms part of a spectrum of related disorders referred to as the autism spectrum disorders (ASDs). Although symptoms can range from mild to severe, those affected typically exhibit severe impairments in social interaction and communication, and engage in repetitive, solitary activities.

The complex nature of the disorder makes it difficult to diagnose. In the absence of any biological marker, clinicians have been typically forced to rely on parental reports, home videos and direct observations of behavior, using standardized tools like the Checklist for Autism in Toddlers (CHAT). But these tools were designed for children 18 months and older; there has been no instrument to measure autistic behaviors in young infants.

So the Canadian researchers designed their own. Led by Susan Bryson, Craig Chair in Autism Research at the IWK Health Centre/Dalhousie University, and co-lead investigator for the study, they developed the Autism Observation Scale for Infants (AOSI). The scale maps the development of infants as young as six months against 16 specific risk markers for autism, including such behaviors such as not smiling in response to the smiles of others or not responding when one's name is called.

"The predictive power of these markers is remarkable", says Dr. Zwaigenbaum. "We are finding that within this high-risk group of siblings, almost all of the children who are diagnosed with autism by age two years have seven or more of these markers by the time they are a year old."

The researchers found that even at six months of age there were certain behaviors that distinguished those siblings later diagnosed with autism from other siblings. These included a passive temperament and decreased activity level at age six months, followed by extreme irritability, a tendency to fixate on objects, reduced social interaction and lack of facial expression as they approached the age of 12 months. At one year, these same children also showed difficulties with language and communication they used fewer gestures, understood fewer phrases and had lower scores for both expressive and receptive language.

It is not known whether these risk markers constitute an early manifestation of the disorder, or are behaviors that reduce the child's opportunities to learn from social experiences, thereby contributing to a pattern of development that may lead to autism. Still, the results shed new light on when autism starts and how early it can be detected.

"This is an important breakthrough in our understanding of the initial behavioral signs of autism," says Peter Szatmari, Director of the Offord Centre and a member of the Canadian research team. "By identifying these signs in children as soon as they are detectable, clinicians will be able to diagnose earlier, interventions can begin earlier, and we can improve the long-term outcomes for these children."

Jessica Brian, who with Wendy Roberts is one of two investigators at The Hospital for Sick Children working on the study, has already developed and begun to evaluate innovative interventions for infants showing early signs.

John Kelton, dean and vice-president of McMaster's Faculty of Health Sciences, said: "This is an important step forward. The team at the Offord Centre is making a real difference towards better care for children and families affected by autism."

Autism Conference Reports Advances in Early Diagnosis

Fri, 06 May 2005 15:53:38 PST

( from http://www.rxpgnews.com ) Some 700 scientists from around the world who gathered in Boston this week shared exciting advances in understanding the causes of and treatments for autism disorders, which affect up to one of every 166 people. Autism is a brain disorder that can severely impair a child's communication and social skills, leaving them in apparent isolation from their families and communities.

"A critical mass of scientists and the new tools of molecular biology are deepening our understanding of autism at a breathtaking pace," said Helen Tager-Flusberg, chair of the conference and a professor at the Boston University School of Medicine. "The immune system, behavior, genetics, and the environment all factor in to this complex and devastating disease. We are putting the pieces together."

Among the advances reported by scientists were:

* Early Detection: Identification of both potential biological markers in the blood (biomarkers) and behaviors that will allow scientists and physicians to identify autism in infants, and thus initiate early treatment.
* Immune System: Strong evidence that autism may be a disorder involving the immune system as well as a disorder of the brain.
* Genetics: Studies homed in on chromosomal regions implicated in autism. Exciting results came from looking at autistic-like traits.
* Environment: Scientists documented overlap between environmentally responsive genes and genes associated with autism, and found evidence into the potential role of environmental toxins such as PCBs.

Scientists reported their findings at the 4th International Meeting for Autism Research (IMFAR). The UC Davis M.I.N.D. Institute, Cure Autism Now, and the National Alliance for Autism Research initiated the annual conference, which is the most extensive exploration of research advances in autism.

Early Detection

Scientists reported progress in being able to diagnose the youngest children through both biomarkers and behavioral observations.

"Whereas today most autistic children are not diagnosed until they are two to three years old, detection in infants would allow early treatment, which can profoundly benefit some children with autism," said David G. Amaral, research director at the UC Davis M.I.N.D. Institute. "And, ultimately, finding biological markers in infants may also yield the fastest route to a cure."

Reports on scientific advances in early detection included:

Biomarkers: Amaral reported on a comparison of blood samples from 70 autistic children and 35 same age normally developing children revealed differences in proteins, metabolites and the immune system. These included elevated levels of immune system B cells and natural killer cells in the autistic group, and more than 100 proteins that the two groups expressed differently.

Behavior: Researchers identified a variety of behaviors, some identifiable in the first year of life, that are predictive of autism. Lonnie Zwaigenbaum at McMaster University in Hamilton, Canada, reported that vocal differences at 12 months were predictive of autism in high-risk infants (those with older siblings who have autism, and Sally Rogers of the UC Davis M.I.N.D. Institute and Marian Sigman of UCLA found that at 12 months, high-risk infants are less likely to respond to their own name than low-risk infants. Other predictive behaviors in very young children included abnormalities in gesture, eye contact, body or limb posturing, and atypical sounds and words.

In addition, two studies showed that clinical diagnoses can be made reliably at 14 to 18 months of age. This is a major advance over current clinical practice, which diagnoses children between ages three and four.

Immune System

Although autism is considered a disorder of the brain, emerging evidence indicates that it may be a disorder of the immune system as well. For instance, a study by Judy Van de Water at the UC Davis Center for Children's Environmental Health and UC Davis M.I.N.D. Institute reported differences in protein molecules called cytokines. The study compared immune cell responses between autistic and typically developing same-age children aged two to five. One difference appeared in response to bacteria, with cells from the autistic group having lower levels of cytokines, which help mediate the body's overall immune response and can also affect mood and behavior. Scientists say the potential connection of cytokines to autism is an intriguing area of research that warrants further investigation.

Genetics

Autism has a strong genetic component, and estimates are that five to 20 genes are likely involved in the condition. Some of these genes may be responsible for inherited traits that by themselves do not cause autism, but may be associated with it. These traits, called endophenotypes, can be behavioral or biological. Scientists are identifying such traits in the family members of autistic children.

"As we identify endophenotypes and their related genes, such as for language delay, we will be homing in on genes for autism," said Daniel Geschwind of the University of California, Los Angeles, School of Medicine. "This is one of the most exciting developments in the field of autism genetics today."

Scientists at the conference reported on endophenotypic traits such as large head size in family members, parents' abnormal brain processing of faces, and the degree to which relatives of autistic children can read another person's mental state. One recent study by Geschwind and his colleagues validated the importance of endophenotypes in teasing out the genetics of autism. The study identified autism-related regions of the genome in children who are part of the AGRE consortium (the largest publicly available collection of autism families). Using the Social Responsiveness Scale (SRS), an instrument that rates 65 behaviors to measure the severity of a child's symptoms and social impairments, the scientists found that the SRS is a powerful tool to detect genetic loci for autism-related social impairment. Specifically they found evidence supporting the location of genes for autism on chromosomes 11 and 17, as well as in a number of other regions of the genome.

Environment

The number of children diagnosed with autism has increased significantly in recent years, leading many scientists to think that non-genetic factors in the environment may be at least partially responsible. Studies that investigated this possibility included:

PCBs and Language Development
Dr. Tal Kenet, Michael Merzenich, and Isaac Pessah at the University of California, San Francisco and Davis, found that rats' exposure to polychlorinated biphenyls (PCBs) showed disturbances in the development of the brain's auditory cortex, but without affecting hearing. However, in humans such brain defects would almost certainly disturb language development in ways typical of autism, the researchers said. The study suggests that environmental factors may combine with genetic predispositions to contribute to the increased incidence of autism.

Environmentally Sensitive Genes Overlap with Genes Associated with Autism
Dr. Martha Herbert at Massachusetts General Hospital found at least 51 overlapping genes when her team compared a scan of the Environmental Genome Project database with published autism genome scans. In addition, children with Autism Spectrum Disorder who possessed alterations within one or more of these 51 genes were likely to exhibit altered susceptibility to environmental toxicants.

Additional Studies

Other reported studies evaluated the effectiveness of behavioral treatments; costs of healthcare for children with autism; changes in the prevalence of autism; mental processes behind special skills in autistic people; and brain anatomy and development associated with autism.

"All of these studies reflect only a small snapshot of the wealth of insight and experience being accumulated by today's scientists," Amaral said. "It is heartening for parents, doctors and scientists to see this progress, while also knowing the distance we have yet to go to prevent and treat, and perhaps one day cure, autism."

Children with Autism have Different Immune System Responses

Fri, 06 May 2005 15:53:38 PST

( from http://www.rxpgnews.com ) 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.

Failed Attention to Faces May Lead to Autism Later

Fri, 06 May 2005 15:53:38 PST

( from http://www.rxpgnews.com ) A leading scientist trying to understand and treat autism suspects that a failure to engage in such normal social activities as looking at a parent's face or listening to speech sounds early in life may help explain the profound impairments in social and language development shown by most children with the disorder.

Geraldine Dawson, director of the Autism Center at the University of Washington, will deliver the keynote address today at the 4th International Meeting for Autism Research being held at the Marriott Boston Copley Place. The meeting will attract leading scientists from around the world, who will discuss research on genetic factors, brain research, new treatments and potential environmental factors involved in the development of autism.

Dawson, also a UW psychology professor, said her team has begun testing a new intervention program for toddlers with autism that not only has a dual focus on language and cognitive development but also promotes the emotional relationship between a child and other people.

"We are examining whether this very early intervention that focuses on social engagement alters the course of development," she said. "As part of our outcomes, we will be examining the child's brain responses to social stimuli. We hope to find that our intervention not only affects behavior but also alters the trajectory of early brain development toward a more normal one."

Most interventions for children with autism are designed for children of preschool age or older, and there are few such programs for toddlers. The UW program, however, treats children as young as the researchers can reliably diagnosis with autism, some just 18 months of age. The program was designed with the assistance of Sally Rogers, a professor of psychiatry at the University of Colorado Health Sciences Center.

The intervention program is intensive, running 25 to 30 hours per week over a two-year period. It involves cognitive and motor skills, and also has a strong focus on emotional and social relationships, Dawson said. The intervention includes such things as children playing games that encourage social activities with their parents or a therapist. The games are modeled after typical parent-infant games, such as patty-cake, that focus on shared communication and enjoyment.

Previous studies by Dawson and her colleagues have shown that preschool-age children with autism do not show typical brain responses to faces and speech sounds, but they do have normal responses toward objects. By 7 or 8 months of age a typically developing a baby's brain waves register differences between two speech sounds and between familiar and unfamiliar faces. Children with autism, however, do not show such differences at 3 and 4 years of age.

Other research has shown that normal development of the brain systems involved in speech and face perception requires early stimulation. Dawson said that a study of American infants exposed to the sounds of Mandarin Chinese that was led by colleague Patricia Kuhl, co-director of the UW's Institute for Learning and Brain Sciences, has important implications for understanding autism.

In that study, groups of 9-month-old infants were shown exactly the same material in Mandarin. One group had the material presented in person by a Mandarin speaker with whom they could interact socially. The other group saw the speaker only on a videotape. Only the brains of children exposed to the speaker with whom they could interact socially learned to distinguish different sounds in Mandarin.

Similarly, children with autism are not able to distinguish English sounds, according to Dawson.

"For speech perception to develop normally, a baby not only must hear speech sounds, but the baby also must be actively engaged in social interaction that involves speech. In other words, the emotional and social relationship is critical for normal social and language brain development to occur. The infant or toddler with autism appears to lack a normal preference or interest for social and language information and fails to actively attend to other people," she said.

Dawson hopes that by teaching toddlers with autism how to interact socially, this will influence the way the children's brain process language and facial information.

PTEN gene of Cowden Syndrome found in Autism

Fri, 08 Apr 2005 01:35:38 PST

( from http://www.rxpgnews.com ) A gene that is changed in many forms of cancer has also been found to show similar changes in some forms of autism, according to preliminary research.

The gene, known as PTEN, was found to be changed, or mutated, in three of 18 people with larger than normal heads and autism spectrum disorder. Autism spectrum disorder includes classical autism, Rett syndrome and other conditions.

The study was led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital (OSU CCC-James) and Richard J. Solove Research Institute and at Childrens Mercy Hospitals and Clinics, Kansas City, Mo.

Inherited gene mutations in the PTEN gene are seen in Cowden syndrome, a poorly recognized disorder that increases a persons risk of developing cancers of the breast, thyroid and uterus. PTEN mutations are also found in several non-inherited (i.e., spontaneous) cancers, including thyroid and endometrial cancers and some brain tumors.

The findings, published in the April Journal of Medical Genetics, raise the possibility that some people with autism and large heads may have an increased risk of cancer.

If our findings are verified, I think that patients with classical autism or autism spectrum disorders and who have large heads should be offered genetic counseling and testing for PTEN mutations, says principal investigator Charis Eng, professor of internal medicine and director of the clinical cancer genetics program at the OSU CCC-James.
If our findings are verified, I think that patients with classical autism or autism spectrum disorders and who have large heads should be offered genetic counseling and testing for PTEN mutations.

Those with PTEN mutations should be offered cancer surveillance like anyone with Cowden syndrome or other syndromes involving PTEN mutations and an elevated risk of cancer.

PTEN is a tumor-suppressor gene, and normally helps prevent cells from becoming cancerous. When a mutation silences tumor-suppressor genes, it can place a person at higher-than-usual risk of developing cancer during his or her lifetime.

Autism is a developmental disorder that typically appears by age 3. It has a prevalence of four to 10 cases per 10,000 people. It is three to four times more common in males than females. People with autism typically show impaired social interactions; impaired verbal and nonverbal communications; repeated body movements, such as hand flapping or rocking; attachment to objects; and resistance to changes in routine.

This study involved 18 children 3 to 18 years of age and diagnosed with ASD and having an enlarged head, a condition known as macrocephaly. The patients head circumference placed them in the 97th to 99th percentile for head size for their age and sex.

Twelve of the 18 patients were identified during clinic visits; six, who had classic autism and macrocephaly, were selected from the Autism Genetic Resource Exchange, a gene bank for autism.

Of the 18 patients, three males (17 percent) age 2 to 4 years showed mutations in the PTEN gene. The locations of the mutations in the PTEN gene are different from those seen in people with cancer, Eng notes, but that may not matter.

Tumor suppressor genes can be silenced in many ways, she says, and if the gene does not function, it can raise the lifetime risk of cancer.

Autism linked to increased oxidative stress

Sun, 03 Apr 2005 10:32:38 PST

( from http://www.rxpgnews.com ) Chronic biochemical imbalance is often a primary factor in the development of many complex diseases but a possible metabolic basis for autism has not been well explored. Now Arkansas Children's Hospital Research Institute researchers report for the first time that children with autism have a severely abnormal metabolic profile indicating increased vulnerability to oxidative stress. The scientists also identified a significant increase in the frequency of several genetic polymorphisms that they believe may increase the risk of autism in specific combinations yet to be determined.

Autism is a neurodevelopment disorder characterized by impairment in social interactions, limited language acquisition, repetitive behaviors, and restricted interests. Usually diagnosed before the age of three, the disorder appears to have increased tenfold over the last 15 years, now affecting more than 30 of every 10,000 children in the United States. Although both genetic and environmental factors are believed to contribute to the development of autism, no firm causal evidence exists. And with no available physiological or biochemical markers, diagnosis currently is made entirely on a behavioral basis.

Dr. James and colleagues measured plasma levels of the major intracellular antioxidant glutathione and its metabolic precursors in 95 autistic children and 75 children without autism. Glutathione levels (and also the ratio of reduced to oxidized glutathione or redox ratio) were significantly decreased in the autistic children, indicating presence of a significant level of oxidative stress. Oxidative stress occurs when the antioxidant system fails to counteract the generation or exposure to free radicals. Unopposed free radicals can damage sensitive cells in the brain, the gastrointestinal tract, and the immune system, and the researchers believe they may contribute to the neurological, gastrointestinal and immunologic pathology that occurs in autistic children.

Working with a larger number of autistic (360) and non-autistic controls (205), the researchers then looked at common polymorphisms in genes that could directly or indirectly affect these metabolic pathways and induce oxidative stress. Three (the catecho-O-methyltransferase gene, the transcobalamin II gene, and the glutathione-S-transferase M1 gene) were found to be significantly elevated in the autistic children. These genes are prevalent in the general population, says Dr. James, and clearly do not "cause" autism. However, she and her colleagues believe specific combinations of these and additional genetic changes could promote the chronic metabolic imbalance seen in the children and thus increase the risk of the disorder.

The next step, says Dr. James, is to determine whether the metabolic profile discovered by the researchers could be used as a diagnostic test for autism to support the purely behavioral diagnosis currently in use. It also would be important, she says, to determine whether the abnormal profile is present in high-risk children, such as toddler siblings of autistic children and/or toddlers with developmental delays.

Autism linked to MIRROR NEURON Dysfunction

Wed, 30 Mar 2005 03:04:38 PST

( from http://www.rxpgnews.com ) According to the new study, currently in press at the journal Cognitive Brain Research, electroencephalograph (EEG) recordings of 10 individuals with autism show a dysfunctional mirror neuron system: Their mirror neurons respond only to what they do and not to the doings of others.

Mirror neurons are brain cells in the premotor cortex. First identified in macaque monkeys in the early 1990s, the neurons also known as "monkey-see, monkey-do cells" fire both when a monkey performs an action itself and when it observes another living creature perform that same action. Though it has been impossible to directly study the analogue of these neurons in people (since human subjects cannot be implanted with electrodes), several indirect brain-imaging measures, including EEG, have confirmed the presence of a mirror neuron system in humans.

The human mirror neuron system is now thought to be involved not only in the execution and observation of movement, but also in higher cognitive processes language, for instance, or being able to imitate and learn from others' actions, or decode their intentions and empathize with their pain.

Because autism is characterized, in part, by deficits in exactly these sorts of social interaction and communication skills, previous research has suggested that a dysfunctional mirror neuron system may explain the observed pathology. The current findings, the researchers say, lend substantial support to the hypothesis.

The UC San Diego team collected EEG data in 10 males with autism spectrum disorders who were considered "high-functioning" (defined as having age-appropriate verbal comprehension and production and IQs above 80) and 10 age- and gender-matched control subjects.

The EEG data was analyzed for mu rhythm suppression. Mu rhythm, a human brain-wave pattern, is suppressed or blocked when the brain is engaged in doing, seeing or imagining action, and correlates with the activity of the mirror neuron system. In most people, the mu wave is suppressed both in response to their own movement and to observing the movement of others.

Subjects were tested while they moved their own hands and while they watched videos of visual white noise (baseline), of bouncing balls (non-biologic motion) and of a moving hand.

As expected, mu wave suppression was recorded in the control subjects both when they moved and when they watched another human move. In other words, their mirror neuron systems acted normally. The mirror neurons of the subjects with autism spectrum disorders, however, responded anomalously only to their own movement.

"The findings provide evidence that individuals with autism have a dysfunctional mirror neuron system, which may contribute to many of their impairments especially those that involve comprehending and responding appropriately to others' behavior," said Lindsay Oberman, first author of the paper and UCSD doctoral student working in the labs of senior authors V.S. Ramachandran, director of the Center for Brain and Cognition, and Jaime Pineda, director of the Cognitive Neuroscience Laboratory.

The current study, the researchers say, adds to understanding the neural basis of autism and may point the way to early diagnosis and to potential therapies.

A first step, Ramachandran said, might be to test those individuals who seem to have a greater genetic likelihood of autism: the younger siblings of those already diagnosed.

Though EEG is not at present designed to measure the brain rhythms of low-functioning autistics whose many repetitive movements confound EEG signals and where mental retardation also plays a significant role in behavioral deficits it can be used as a tool for earlier diagnosis of high-functioning autistics, whose disorder today is typically not recognized until age 3 or 4 and often later.

Earlier diagnosis in turn could lead to earlier interventions. One therapeutic possibility suggested by the study's findings is biofeedback.

Pineda, who also works on a number of brain-computer interface projects, says that the mu rhythm is one that we most readily learn to control.

"We can learn to increase or decrease the strength of the mu signal at will. By imagining action, subjects are able to move a paddle in a computer game of 'Pong' after just four to six hours of practice," he said. "Because this rhythm is one that we have access to volitionally, it may prove useful in therapy."

Another possible therapy would involve ordinary mirrors. Ramachandran has successfully treated amputees who experience pain or paralysis in their missing, or "phantom," limbs by using a mirror reflection of their healthy limb to "trick" their brains into believing that the missing limb has been restored to pain-free motion. Since autistics' mirror neurons respond to their own motion, the researchers say, perhaps their brains can be induced to perceive their own reflected movements as the movements of another human being.

"We have a long way to go before these therapeutic possibilities are a reality, but we're that much closer now that we've linked autism to a specific region of the brain," said Ramachandran. "More than just documenting a brain anomaly in autism, we've been able to relate symptoms that are unique to the disorder loss of empathy and imitative skills to the function of a particular circuit, the mirror neuron system."

Other authors on the study are: Eric Altschuler, former UCSD postdoctoral researcher now at the Mt. Sinai School of Medicine in New York, who with Ramachandran and Pineda originally presented preliminary findings on mirror neuron dysfunction in one autistic child in 2000; Edward Hubbard, recent UCSD graduate now at the French National Institute of Health (INSERM) in Paris; and UCSD graduate student Joseph McCleery.

The team is now pursuing another, related line of research: Are mirror neurons involved in the ability to understand metaphors? Autistic individuals typically have difficulties with metaphors, often interpreting them literally, and the researchers believe this too may be connected to a dysfunctional mirror neuron system.

"Even as the clinical study of mirror neurons is giving us insights into autism and other disorders," Ramachandran said, "it is also giving us glimpses of a host of uniquely human and elusive mental capacities: making metaphors and passing on proverbs, to name just two."

Fragile X syndrome is marked by autism-like symptoms

Thu, 18 Mar 2004 01:43:38 PST

( from http://www.rxpgnews.com ) People with fragile X syndrome, the most common inherited developmental disability, have reduced blood levels of a protein vital for brain development and function, researchers at the School of Medicine have found. These lowered levels are linked to abnormal activity patterns in the brain.

It is exciting to think that a biological marker we can measure in the blood is correlated with vital brain function, said Allan Reiss, MD, professor and director of the Stanford Psychiatry Neuroimaging Laboratory and Behavioral Neurogenetics Research Center in the Department of Psychiatry and Behavioral Sciences and the study's senior author.

These sets of images show brain regions where there was significant activation during the response inhibition tasks used to compare activity in fragile X brains (blue) with typically developing brains (red). Photo: Courtesy of Vinod Menon

Additionally, in people with fragile X syndrome, researchers found that background brain activity outside the realm of problem solving does not decrease as expected when the individual is confronted with a complex task. In unaffected people, the brain smoothly redirects resources to other tasks as needed. This may explain why people with fragile X can't produce cognitive resources when needed.

The findings, published March 1 in the Proceedings of the National Academy of Sciences, will enable a more targeted approach to the development of treatments for the disorder.

Fragile X syndrome is so named because it results from a mutation of a gene at a fragile site on the X chromosome where structural gaps may occur. It affects roughly 1 in 3,600 males and 1 in 4,000 to 6,000 females, according to the National Fragile X Foundation.

The mutation arises when a repetitive DNA segment of a gene known as FMR1 expands up to hundreds or thousands of times. The FMR1 gene normally produces fragile X mental retardation protein, which regulates the production of other proteins controlling how nerve synapses grow and change in response to learning.

Males with fragile X syndrome produce little or no fragile X protein. They also have severe manifestations of the disease, including autistic-like behaviors, hyperactivity and mental retardation. Affected females often have less extreme symptoms such as attention deficit, shyness, anxiety and learning problems, although some may show autistic behavior and mental retardation.

Such a broad spectrum of severity in females corresponds to a wide range of brain activation patterns and blood levels of fragile X protein. This range makes females particularly fitting subjects for studying the association between the protein levels and brain activity in individuals with fragile X syndrome.

The effect of genetic factors on brain function is a topic of increasing interest within the field of cognitive neuroscience, and fragile X syndrome provides an excellent model to investigate the effect of a single gene on human brain function said first author Vinod Menon, PhD, associate professor of psychiatry and behavioral sciences and a member of Stanford's neurosciences program.

Menon, Reiss and colleagues examined whether reductions in brain activation are correlated with levels of fragile X mental retardation protein in the blood. In previous studies the researchers had shown that individuals with performance deficits had reduced brain activity in regions known to be associated with the tasks being performed. They conducted the current study to shed light on whether the reduced brain activity observed was simply a function of poor performance or the result of faulty neural processing.

The study, funded by the National Institutes of Health with support from the Canel Family Fund, observed 18 females ages 10-22 who had the gene mutation that causes fragile X syndrome, and for comparison, 16 typically developing age-matched females. Study subjects performed a series of tasks while undergoing an MRI that allows researchers to monitor brain activity. The method tracks changes in blood oxygen levels as a marker for changes in blood flow that, in turn, are closely correlated to nerve cell activity in the brain.

The so-called response inhibition task researchers used was simple, addressing the ability to control impulsive behavior. Subjects were shown different letters of the alphabet that flashed one at a time on a computer screen. They were asked to respond by pressing a key in every case except when they saw the letter X. The first task was a Go task, in which the letter X never appeared and in this way subjects were allowed to build up a tendency to respond. Immediately afterward, subjects performed a Go/No Go task in which the letter X did appear in the lineup, at which point the subject had to control the previously built impulse to respond. Statistical correlations were made between observed reduction in brain activity compared with typically developing individuals and the levels of fragile X mental retardation protein found in blood samples taken from each subject.

Individuals with fragile X syndrome performed the response inhibition task as well as normally developing people, so the observed differences in brain activity could not be attributed simply to performance deficits. Among the participants with fragile X, brain activity decreased in key areas involved in response inhibition in proportion to fragile X protein levels. We are particularly excited to have a marker for this condition that gives us a tool to begin to query associations across multiple scientific levels including genetic, brain function and behavior, said Reiss. The study brings neuroscience and psychiatry together in a unique way.

The work is part of a comprehensive research program at Stanford directed by Reiss and devoted to studying fragile X syndrome and other genetic and neurodevelopmental disorders that affect learning, behavior and development in children. The research team plans to expand brain imaging research to test other cognitive and behavioral functions with the disorder, integrating knowledge gained from genetic, physiological and behavioral studies. They are recruiting preschoolers, children and adolescents for ongoing studies to determine, among other things, the timing, amount and type of effective interventions.

http://spnl.stanford.edu/publications/pdfs/Menon_FX_FMR1PNAS04.pdf

Individuals with fragile X syndrome or other causes of developmental disability are encouraged to participate in this study. Call (888) 411-2672 or e-mail vanstone@stanford.edu for more information.