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Tuesday, November 16, 2010 Vol. 14 No. 100RESEARCH
Brain Scans Detect Autism's Signature
Modeling Rett Autism in a Lab Dish: Researchers Create Autistic Neuron Model
Strep Throat May Be Linked to OCD, Autism-Spectrum Disorders
TREATMENT
Study Reveals Children Recover From Autism With Intensive Three-Year Behavioral Therapy
N-Acetylcysteine Reduces Irritability in Autistic Kids: Phase II Study
NEWS
Keeping Babies Off Cow's Milk May Help Prevent Childhood Diabetes: Study
PEOPLE
Oregon With Autism And His Service Dog Attend First Day Of School Together
Care Worker Accused Of Stealing £3,500 From Autistic Woman
RESEARCH
Brain Scans Detect Autism's Signature
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ScienceDaily — An autism study by Yale
School of Medicine researchers using functional magnetic resonance
imaging (fMRI) has identified a pattern of brain activity that may
characterize the genetic vulnerability to developing autism spectrum
disorder (ASD). Published November 15 in the early edition of
Proceedings of the National Academy of Sciences, the study could
eventually lead to earlier and more accurate autism diagnosis. ASD is defined by impaired social interaction and communication, and can disrupt the brain's |
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| Brain scans. An autism study using functional magnetic resonance imaging (fMRI) has identified a pattern of brain activity that may characterize the genetic vulnerability to developing autism spectrum disorder (ASD). (Credit: iStockphoto/Steve Greer) |
Using fMRI, Yale researchers Martha Kaiser, Kevin Pelphrey and colleagues scanned the brains of children with autism and their unaffected siblings, as well as those of typically developing children as the three groups watched animations of biological movement. The study included 62 children age 4 to 17.
The team identified three distinct "neural signatures": trait markers -- brain regions with reduced activity in children with ASD and their unaffected siblings; state markers -- brain areas with reduced activity found only in children with autism; and compensatory activity -- enhanced activity seen only in unaffected siblings. The enhanced brain activity may reflect a developmental process by which these children overcome a genetic predisposition to develop ASD.
"This study may contribute to a better understanding of the brain basis of ASD, and the genetic and molecular origin of the disorder," said first author Kaiser, a postdoctoral associate in the Yale Child Study Center.
Other authors on the study from Yale include Caitlin Hudac, Sarah Shultz, Su Mei Lee, Celeste Cheung, Allison Berken, Ben Deen, Naomi Pitskel, Daniel Sugrue, Avery Voos, Celine Saulnier, Pamela Ventola, Julie Wolf, Ami Klin, Brent Vander Wyk and Kevin Pelphrey.
The study was supported by grants from the Simons Foundation, the National Institute of Mental Health, Autism Speaks, The John Merck Scholars Fund, and the Natural Sciences and Engineering Research Council of Canada.
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Modeling Rett Autism in a Lab Dish: Researchers Create Autistic Neuron Model
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Human induced pluripotent stem (iPS) cells derived from patients with Rett syndrome allow researchers to replicate autism in the lab and study the molecular pathogenesis of the disease. (Credit: Illustration courtesy of Jamie Simon, Salk Institute for Biological Studies)
ScienceDaily — A collaborative effort between researchers at the Salk Institute for Biological Studies and the University of California, San Diego, successfully used human induced pluripotent stem (iPS) cells derived from patients with Rett syndrome to replicate autism in the lab and study the molecular pathogenesis of the disease.
Their findings, published in the Nov. 12, 2010, issue of Cell, revealed disease-specific cellular defects, such as fewer functional connections between Rett neurons, and demonstrated that these symptoms are reversible, raising the hope that, one day, autism maybe turn into a treatable condition.
"Mental disease and particularly autism still carry the stigma of bad parenting," says lead author Alysson Muotri, Ph.D., an assistant professor in the Department of Molecular and Cellular Medicine at the University of California, San Diego School of Medicine. "We show very clearly that autism is a biological disease that is caused by a developmental defect directly affecting brain cells."
Rett syndrome is the most physically disabling of the autism spectrum disorders. Primarily affecting girls, the symptoms of Rett syndrome often become apparent just after they have learned to walk and say a few words. Then, the seemingly normal development slows down and eventually the infants regress, loosing speech and motor skills, developing stereotypical movements and autistic characteristics.
Almost all cases of the disease are caused by a single mutation in the MeCP2 gene, which is involved in the regulation of global gene expression, leading to a host of symptoms that can vary widely in their severity.
"Rett syndrome is sometimes considered a 'Rosetta Stone' that can help us to understand other developmental neurological disorders since it shares genetic links with other conditions such as autism and schizophrenia," says first author Carol Marchetto, Ph.D., a postdoctoral researcher in the Laboratory of Genetics at the Salk Institute.
In the past, scientists had been limited to study the brains of people with autistic spectrum disorders via imaging technologies or postmortem brain tissues. Now, the ability to obtain iPS cells from patients' skin cells, which can be encouraged to develop into the cell type damaged by the disease gives scientists an unprecedented view of autism.
"It is quite amazing that we can recapitulate a psychiatric disease in a Petri Dish," says lead author Fred Gage, Ph.D., a professor in the Salk's Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases. "Being able to study Rett neurons in a dish allows us to identify subtle alterations in the functionality of the neuronal circuitry that we never had access to before."
Marchetto started with skin biopsies taken from four patients carrying four different mutations in the MeCP2 gene and a healthy control. By exposing the skin cells to four reprogramming factors, she turned back the clock, triggering the cells to look and act like embryonic stem cells. Known at this point as induced pluripotent stem cells, the Rett-derived cells were indistinguishable from their normal counterparts.
It was only after she had patiently coaxed the iPS cells to develop into fully functioning neurons -- a process that can take up to several months -- that she was able to discern differences between the two. Neurons carrying the MeCP2 mutations had smaller cell bodies, a reduced number of synapses and dendritic spines, specialized structures that enable cell-cell communication, as well as electrophysical defects, indicating that things start to go wrong early in development.
Since insulin-like growth factor 1 (IGF-1) -- a hormone which, among other things, has a role in regulating cell growth and neuronal development -- was able to reverse some of the symptoms of Rett syndrome in a mouse model of disease, the Salk researchers tested whether IGF-1 could restore proper function to human Rett neurons grown in culture.
"IGF-1 treatment increased the number of synapses and spines reverting the neuronal phenotype closer to normal," says Gage. "This suggests that the autistic phenotype is not permanent and could be, at least partially, reversible."
Muotri is particularly excited about the prospect of finding a drug treatment for Rett syndrome and other forms of autism: "We now know that we can use disease-specific iPS cells to recreate mental disorders and start looking for new drugs based on measurable molecular defects."
Researchers who also contributed to the work include Cassiano Carromeu and Allan Acab in the Department of Pediatrics/Cellular & Molecular Medicine at the University of California, San Diego, Diana Yu and Yangling Mu in the Laboratory of Genetics at the Salk Institute for Biological Studies, Gene Yeo in the School of Medicine at the University of California, San Diego, as well as Gong Chen in the Department of Biology at the Pennsylvania State University.
This work was supported by the Emerald Foundation Young Investigator Award, the National Institutes of Health through the NIH Director's New Innovator Award Program, the California Institute for Regenerative Medicine, The Lookout Fund and the Picower Foundation.
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Strep Throat May Be Linked to OCD, Autism-Spectrum Disorders
By Mary Rice xrl.in/6o28
In a research paper due to be published next year, an Israeli research team has linked children’s strep throat to obsessive-compulsive disorder. A condition called PANDAS, it is estimated that 1 to 2 percent of children who get strep throat develop this complication. This strep-OCD link could also account for some autism and tic-spectrum disorders in children.
Strep linked to OCD in children In a study on rats in Tel Aviv, a team of researchers has linked strep throat infections to causing obsessive-compulsive disorders. This connection has long been theorized and is generally known as PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. This is when children develop OCD or tic disorders soon after catching strep throat or scarlet fever. The streptococcal bacteria causes the body to produce, and in some cases overproduce, antibodies that bind to dopamine receptors in the brain. This binding changes how the neurotransmitters work, and in some cases causes obsessive-compulsive disorder and tic disorders such as Tourette’s syndrome.
Strep link could have autism implications The study that links strep throat with OCD could have implications on diagnoses and treatment of rapid-onset autism. OCD and autism are often, though not always, linked. In some children, the onset symptoms of OCD and autism can be very similar. Though this study did not find that a strep throat infection “run wild” could cause autism, it could be one more piece in the puzzle of neurological conditions.
Treating OCD and tic disorders through strep The linking of strep throat and streptococcal infections with OCD and tic disorders has important implications for the treatment of these brain conditions. For children who show a rapid onset of neurological symptoms, treatment with high doses of powerful antibiotics could reduce the antibodies in the blood that bind with dopamine receptors. This highlights the ongoing issue with antibiotic resistance and over-prescription, however, because the streptococcal bacteria has been showing increased resistance. Be sure that if your child is being given antibiotics it is for a bacterial infection, not a viral one.
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TREATMENT
Study Reveals Children Recover From Autism With Intensive Three-Year Behavioral Therapy
From an organization announcement.
The Center for Autism and Related Disorders announces the outcomes of its study on 14 children with autism, who achieved substantial levels of growth, including the removal of the autism diagnosis with nearly half of the participants.
A landmark study conducted by the Center for Autism and Related Disorders, Inc. (CARD), the world’s largest provider of early intensive behavioral intervention for children with autism, shows children with autism are capable of making dramatic gains across all areas of functioning, including recovery from autism. The report was released, November 11th in Phoenix, Arizona by CARD Founder and Executive Director / Behavior Analyst Dr. Doreen Granpeesheh.
Autism is a pervasive developmental disorder that is marked by the presence of impaired social interaction and communication and a restricted repertoire of activities and interests. Autism is currently estimated to affect as many as 1 in 110 children, in America and is four times more common in boys than in girls.
In 2007, the state of Arizona allocated funds for a three-year program that evaluated the effects of behavioral intervention for 14 young children with autism. All children received 25 or more hours per week of one-to-one teaching and therapy, by trained professionals. Their therapy consisted of intensive teaching, based on the principles and procedures of Applied Behavior Analysis (ABA), a scientifically proven treatment for autism. The CARD Model of ABA, which focuses on blending intensive, structured teaching, with less structured, play-based behavioral intervention techniques, was implemented in the study. Treatment plans were based on identifying what motivates the children and based treatment activities on the desires and interests of children involved. As part of the study, the CARD treatment integrated a careful assessment of each child’s strengths and deficits and directly addressed each area of need through targeted teaching programs.
“I have followed the progress of these children over the past three years and the results are spectacular,” says Arizona Senate President-Elect Russell Pearce.
In accordance with previous research, CARD found that many of the children made substantial gains in cognitive and adaptive functioning as well as language skills. Most of the children also demonstrated significant improvements in executive functioning. After treatment, the average T-score for the group on the BRIEF, a measure of overall executive functioning, was 61, well below the cut-off for clinically significant impairment. Parent stress was also decreased dramatically, with a mean post-treatment percentile score of 68, also well below the cut-off for clinical significance. In addition, 8 out of 14 children were functioning in the average range on the Vineland ABC, a measure of overall adaptive functioning, whereas only 2 of 14 were in the average range before treatment began. Dramatic improvements are evident for approximately half of the participants, with 43% of children no longer displaying clinical symptoms of autism.
“My daughter is now recovered from autism,” says Elizabeth Howell, parent of study participant. “When people meet her and interact with her, they cannot believe that she ever had an autism diagnosis. My daughter is an outstanding student in an elementary classroom with typical peers without any aides or support. Our family now does things that we previously only dreamed of doing – we are like every other family on the block.”
Among the study’s major findings is that children who developed language skills early in therapy made greater gains over time. In addition to the children who recovered from autism, the other half of the program participants made substantial gains as well. In addition, children who were most severely affected by autism made substantial gains in their ability to communicate and live independently. Even the children whose progress was the slowest experienced significant decreases in challenging behaviors and increases in independent communication and leisure skills, thereby resulting in improved self-reliance and quality of life.
“The behavioral intervention was intensive, comprehensive, and high-quality,” says Dr. Amy Kenzer, CARD Research Manager. “These factors play a major role in the outcomes observed."
“This project provides further proof that autism is treatable and that behavioral intervention is effective, when done properly,” says Dr. Jonathan Tarbox, CARD Director of Research and Development.
What makes this study unique is the successful partnership between the state of Arizona, CARD (a private agency), and families affected by autism.
“We want to particularly thank the incredible families we worked with,” says Dr. Doreen Granpeesheh. “One of the most important factors that impact the effectiveness of treatment is the involvement and dedication of a child’s parents and we could not ask for better parents than we have the privilege of working with in Arizona."
The program is now a model for the implementation of effective, comprehensive, intensive behavioral intervention for children with autism.
N-Acetylcysteine Reduces Irritability in Autistic Kids: Phase II Study
By Karla Gale xrl.in/6o1u
Reuters Health - In children with autism, N-acetylcysteine (NAC) improved repetitive behaviors in a phase II trial.
In addition, irritability improved significantly within four weeks of starting treatment, the investigators reported yesterday afternoon at the 57th annual meeting of the American Academy of Child and Adolescent Psychiatry in New York City.
One reason for using this antioxidant in these kids is that autism is characterized by a lack of anti-oxidant capacity, explained Dr. Lawrence K. Fung, a psychiatry fellow at Stanford University in California and presenter of the study. Also, he said, children with autism have alterations in the glutamate receptor, and NAC has glutamatergic properties.
Plus, he added, "there have been some good data" showing a benefit of NAC for treatment of trichotillomania, depression, schizophrenia and obsessive-compulsive disorder.
And according to Dr. Hemmo A. Drexhage, an immunologist at Erasmus Medical Center in Amsterdam who wasn't involved with the current study, there's evidence to suggest that autism and other psychiatric disorders are associated with immune system activation that could theoretically respond to NAC.
The 12-week, randomized, double-blind trial included 28 children ages 3 to 12 with Clinical Global Impression Severity rating > 4. The 14 kids assigned to NAC started at a dose of 900 mg/day; the dose was doubled (1800 mg/day) at week 4 and tripled (2700 mg/day) at week 8, Dr. Fung told Reuters Health.
"Roughly half of the subjects were on a range of medications including stimulants, antidepressants and antipsychotics," he added.
Mean ABC (Aberrant Behavioral Checklist) total scores for the NAC group were 69.7, 24.7, 41.8, and 38.7 at baseline, 4 weeks, 8 weeks, and 12 weeks, respectively, the researcher said. By contrast, ABC scores in the placebo group stayed between 68.4 and 56.3 during the same period (p < 0.05).
The irritability subscale of the ABC declined steadily from 16.9 at baseline to 7.3 after 12 weeks of NAC treatment, while hovering between 17.6 and 13.4 with placebo (p < 0.001 at 4 weeks, p < 0.01 at 8 and 12 weeks).
Compared with placebo, NAC was also associated with significant improvement from baseline in the Repetitive Behavior Scale-Revised (p < 0.05) and in Social Responsiveness Scale, mannerisms subscale (p < 0.05).
No significant differences between groups occurred in the Clinical Global Rating Scale, Sensory Profile Questionnaire, or Vineland Adaptive Behavioral Scale.
"NAC was overall well-tolerated with limited side effects," the study abstract says, with no suggestion of sedation.
The study did not take into account behavioral interventions and other medications the children were taking.
Dr. Brian King, a spokesman for the American Academy of Child and Adolescent Psychiatry, commented that while this was a small study, "the signal observed (for irritability) absolutely is something we should pursue."
Dr. King, who's also the director of the Autism Center at Seattle Children's Hospital and professor of psychiatry at the University of Washington, added that the "side effect profile of NAC is very kind."
"I think there will be a lot of interest in pursuing this lead," he said.
Dr. Pria Persaud, from the State University of New York at Stony Brook, however, told Reuters Health that the study was "interesting," but not enough to convince her to use NAC for her autistic patients. "Autistic kids are very sensitive to medications, and I wonder if other drugs they were on could have accounted for the improvements," she said.
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NEWS
Keeping Babies Off Cow's Milk May Help Prevent Childhood Diabetes: Study
By Gene Emery xrl.in/6nkb
Reuters - Researchers said on Wednesday they found some evidence that keeping babies off cow's milk may help prevent the development of type 1 diabetes in children with an inherited risk of the disease.
The children will have to be followed for years to be sure, but the Finnish researchers found indirect evidence that giving the babies a special formula may have helped.
The study of 230 Finnish infants who had stopped receiving breast milk was a preliminary test of the treatment. A much larger study of 2,160 babies, now ongoing in 15 countries, is expected to provide a definitive answer to the question in 2017.
The goal is to prevent type 1 diabetes, which typically strikes in childhood and requires a lifetime of careful management, including regular insulin injections. It is believed to be caused when the body's immune system mistakenly attacks insulin-producing cells in the pancreas.
This study involved infants who only got the formula when breast milk was not available.
Instead of a standard cow's milk formula, about half the babies were given a special formula in which the proteins found in the casein portion of the milk had been broken down into components too small to activate the immune system, a process called hydrolyzation.
Results of the pilot test, reported in the New England Journal of Medicine, showed that babies fed this hydrolyzed formula were less likely to develop telltale antibodies that are believed to pave the way for diabetes.
"Our results indicate that a preventive dietary intervention aimed at decreasing the risk of type 1 diabetes may be feasible," the researchers, led by Dr. Mikael Knip of the University of Helsinki, wrote.
Children given the cow's milk were twice as likely as the other children to develop one or more diabetes-related antibodies. The antibodies took anywhere from 3 months to 10 years to appear.
However, the pilot study was not large enough to tell if avoiding cow's milk reduced the actual risk of diabetes. Eight percent of the cow's milk recipients developed type 1 diabetes, compared to 6 percent who got the special formula, a difference that was not statistically significant.
"We did not expect a 100 percent prevention of clinical disease," Knip said in an e-mail.
All of the babies in the test -- and those in the larger study now underway -- have a genetic susceptibility to diabetes and had at least one family member with type 1 diabetes. They were followed until their 10th birthday.
Finland has one of the highest rates of type 1 diabetes in the world, with 64 new cases per year among every 100,000 children under 15.
• • •
PEOPLE
Oregon With Autism And His Service Dog Attend First Day Of School Together
Wendy Owen, The Oregonian xrl.in/6nkc
Motoya Nakamura/The Oregonian
Curtis Cottengim kisses his autism service dog, Cadbury, during the dog's first week at Howard Eccles Elementary in Canby. When frustration gets the better of the 8-year-old and he loses control, the yellow Labrador nuzzles and licks the boy to help calm him. By the end of his second week, Curtis headed off his frustration by hugging the dog.
Cadbury, a yellow Labrador, hasn't had to perform at school yet, but when he senses a change in his boy's tone of voice, he raises his head and watches the 8-year-old.
If he senses Curtis Cottengim, who has autism, is getting wound up and headed for a tantrum of frustration, he walks to the boy and nuzzles him or licks him. If the behavior explodes and Curtis ends up on the floor, Cadbury will stand over or lie on him. It's usually over in minutes, said Curtis' mom, Robin Cottengim.
Cadbury's first day at school with Curtis was last week at Howard Eccles Elementary in Canby. And, by all accounts, it was a success.
Canby is one of few districts in Oregon that allows an autism service dog in its schools. Beaverton is expecting to allow one this year, but Hillsboro has denied the use of an autism service dog for a 10-year-old boy at one of its elementary schools. The family filed a civil rights complaint a year ago.
Canby lacked an adequate policy to deal with service dogs and created their own, said Jeff Rose, Canby School District Superintendent.
"This is new territory for us," he said. "We're hoping this is beneficial for the student. We do everything we can to accommodate their abilities."
The procedures require the dog's handler be with the animal at all times. In Curtis' case, the handler is his mom.
Last week, Robin Cottengim and Cadbury spent nearly two hours a day in Curtis' classroom, but she hopes to gradually increase that to full days.
On the first day, Cadbury lay near Cottengim, resting but keeping tabs on Curtis.
"My son said something really loud and Cadbury's head popped up. He knew that was his boy," she said.
The Cottengims have had the specially trained Labrador for nearly two months. Cottengim helped the special needs class of seven students adjust to the dog by bringing him for brief visits.
Change is especially difficult for children with autism, which is a developmental disorder that affects a child's ability to interact and communicate with others.
Prior to Cadbury, the staff sometimes had to take Curtis to a padded sensory room where he could lie in a swing and calm down, Cottengim said.
"Usually, his moods will escalate pretty quickly," she said. "He can throw things and hit or kick. He has tried to bite."
Curtis' teacher, Emily Dooley, said the students easily adapted to Cadbury. Last Wednesday, they gathered around the dog, petted him and gave him a treat.
"Our goal is to have Cadbury help create a more therapeutic environment in the classroom," Dooley said.
• • •
Care Worker Accused Of Stealing £3,500
From Autistic Woman
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A care worker looking after a woman with autism and severe learning difficulties stole £3,500 from her bank account over seven months, a court was told.
Care worker Julie Wendy Wells was entrusted to draw cash out using the woman's debit card, but kept much of it for herself, said prosecutor Gareth Evans.
She was supposed to keep written records of money drawn out and receipts for spending, but later claimed the cash books had been lost.
Mr Evans told the jury at Plymouth Crown Court that the victim was a woman of 45 who could not cope alone and needed 24-hour care.
She attended a day centre five days a week from 9am-4pm, being looked after the rest of the time by an agency providing carers.
Mr Evans said: "The reality is that for long periods her sole carer was Julie Wells. She was the sole and principal carer – except when she was enjoying a holiday in Canada."
He said the accounting system allowed for audits and checks and was designed to prevent theft from vulnerable people.
Mr Evans said: "The prosecution say this is a straightforward case of dishonesty of the worst kind."
Wells, aged 55 and from Seaview Terrace, Thurlestone, denies a single charge of theft.
The trial, expected to last three days, is due to continue today.
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