Posts tagged autism
Articles and news from the latest research reports.
Vanderbilt University researchers studying interventions for adolescents and young adults with autism are reporting that there is insufficient evidence to support findings, good or bad, for the therapies currently used.
The researchers systematically screened more than 4,500 studies and reviewed the 32 studies published from January 1980 to December 2011 on therapies for people ages 13 to 30 with autism spectrum disorders. They focused on the outcomes, including harms and adverse effects, of interventions, including medical, behavioral, educational and vocational.
• Some evidence revealed that treatments could improve social skills and educational outcomes such as vocabulary or reading, but the studies were generally small and had limited follow-up.
• Limited evidence supports the use of medical interventions in adolescents and young adults with autism. The most consistent findings were identified for the effects of antipsychotic medications on reducing problem behaviors that tend to occur with autism, such as irritability and aggression. Harms associated with medications included sedation and weight gain.
• Only five articles tested vocational interventions, all of which suggested that certain vocational interventions may be effective for certain individuals, but each study had significant flaws that limited the researchers’ confidence in their conclusions.
A Systematic Review of Vocational Interventions for Young Adults With Autism Spectrum Disorders
Fathers bequeath more mutations as they age
22 August 2012 by Ewen Callaway
Genome study may explain links between paternal age and conditions such as autism.
Older fathers’ sperm have more mutations — as do their children.
V. Peñafiel/Flickr/GETTY
In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.
(Source: nature.com)
Low-Dose Sedative Alleviates Autistic-Like Behavior in Mice With Dravet Syndrome Mutation
ScienceDaily (Aug. 22, 2012) — A low dose of the sedative clonazepam alleviated autistic-like behavior in mice with a mutation that causes Dravet syndrome in humans, University of Washington researchers have shown.
(Credit: © Vasiliy Koval / Fotolia)
Dravet syndrome is an infant seizure disorder accompanied by developmental delays and behavioral symptoms that include autistic features. It usually originates spontaneously from a gene mutation in an affected child not found in either parent.
Studies of mice with a similar gene mutation are revealing the overly excited brain circuits behind the autistic traits and cognitive impairments common in this condition. The research report appears in the Aug. 23 issue of Nature. Dr William Catterall, professor and chair of pharmacology at the UW, is the senior author.
Dravet syndrome mutations cause loss-of-function of the human gene called SCN1A. People or mice with two copies of the mutation do not survive infancy; one copy results in major disability and sometimes early death. The mutation causes malformation in one type of sodium ion channels, the tiny pores in nerve cells that produce electrical signals by gating the flow of sodium ions.
The Catteralll lab is studying these defective ion channels and their repercussion on cell-to-cell signaling in the brain. They also are documenting the behavior of mice with this mutation, compared to their unaffected peers. Their findings may help explain how the sporadic gene mutations that cause Dravet syndrome lead to its symptoms of cognitive deficit and autistic behaviors.
Stem Cell Trial for Autism Launches in U.S.
August 21, 2012
Stem cell treatment could lower inflammation levels and demonstrate whether autism is an autoimmune disease
Image: Nature News
Families with autistic children must navigate a condition where questions outnumber the answers, and therapies remain sparse and largely ineffective. A clinical trial being conducted by the Sutter Neuroscience Institute in Sacramento, California to address this situation began recruiting participants today for a highly experimental stem cell therapy for autism. The institute plans to find 30 autistic children between ages 2 and 7 with cord blood banked at the privately-run Cord Blood Registry, located about 100 miles west of the institute. Already one other clinical trial, with 37 total participants between ages 3 and 12 years old, has been completed in China. The researchers affiliated with Beike Biotechnology in Shenzhen, the firm that sponsored the study, have not yet published any papers from that the trial, which used stem cells from donated cord blood. Mexican researchers are currently recruiting kids for yet another type of autism stem cell trial that will harvest cells from the participant’s fat tissue.
But for each of these officially registered trials, many more undocumented stem cell therapy treatments take place for clients who are willing to pay enough. “Our research is important because many people are going to foreign countries and spending a lot of money on therapy that may not be valid,” says Michael Chez, a pediatric neurologist and lead investigator of the study at Sutter.
A major difference between the Sutter trial and those in China is that his will use the child’s own stem cells, rather than those from a donor. Chez hypothesizes that one way autologous stem cell infusion might work is by reducing inflammation within the body’s immune system. This would answer previous research that suggests that autism may be an autoimmune disease. “One of our exploratory goals will be to look at inflammatory markers in cells,” he says.
The study’s primary goal, however, will be assessing changes in patients’ speaking and understanding of vocabulary. For each individual, researchers will create a baseline benchmark that establishes current skill levels. The group will be evenly divided, with one initially receiving an infusion of their own, unmodified cord blood stem cells and the other a placebo treatment of saline injection. Six months later, all of the children will be tested on their ability to comprehend and form words. The groups will then be switched. In the course of the 13-month-long study, both groups will receive only one stem cell therapy infusion.
Not all stem cell scientists who study neurodevelopmental diseases are ready to invest great hope that the autism stem cell trial will succeed. “I wish I could tell you I’m optimistic about the end results,” says James Carroll, a pediatric neurologist at the Georgia Health Sciences University in Augusta who began a clinical trial two years ago to better understand how stem cell therapy affects patients with cerebral palsy. “But so far we have not seen any kind of miraculous recovery in our cerebral palsy patients. I would be delighted if that changes.”
Members in the stem cell therapy patient community think Chez will have no shortage of volunteers for the trial. Jeremy Lowey, who lives in Sacramento and has struggled with a rare condition known as non-verbal learning disorder, arranged for his own stem cell therapy treatment in India last year, which he called life-changing. He receives numerous Facebook requests from parents of autistic children who are curious to know more. He always begins his conversations by saying, “Go slowly and think hard about your decision.”
Source: Scientific American
New University of Otago research into two sex hormones released by the testes of male fetuses and boys may help solve the enduring mystery of why autism is much more common in boys than girls.
The researchers studied blood samples from 82 boys with ASD and 16 control boys, all aged between 4.4 to 8.9 years. Measuring the levels of the two hormones, the researchers found that these were highly variable from boy to boy, but no different on average between the two groups of boys.
Professor McLennan says the findings indicate that male hormones are important for autism, but not because autistic boys have abnormal levels.
While it has been previously suggested that exposure in the womb to excessive levels of testosterone might be creating an ‘extreme male brain’, this does not explain why some females have autism, or why males with autism do not exhibit an extreme male physical form.
"Our data suggest that the still-elusive primary initiating cause of ASD is common to both males and females, with the condition being more frequent in males because normal levels of male hormones exacerbates the pathology,” he says.
The researchers say that their hypothesis now needs further testing through longitudinal studies of at-risk male babies to determine whether their levels of AMH and InhB early in development can predict the breadth of autistic traits later in life.
(Image credit: ©iStockphoto.com/ktaylorg)
A young autistic boy has found his outlet in making science videos. Jordan Hilkowitz was diagnosed with autism when he was just 18 months old, he didn’t begin to speak until he was 5. His mother Stacey remembers the heartbreak she experienced as she watched her young son bang his head against the wall out of frustration at not being able to communicate.
It was his babysitter’s idea for Jordan to start making science videos. He’d always had an interest in science, and she felt that this could be an outlet for him to communicate to a larger audience. Larger indeed! Jordan’s channel, Doctor Mad Science, has received over 2.4 million views to date – and he’s become a local celebrity for his scientific knowhow.
(Source: blogs.scientificamerican.com)
Research shows gene defect’s role in autism-like behavior
August 10, 2012
Scientists affiliated with the UC Davis MIND Institute have discovered how a defective gene causes brain changes that lead to the atypical social behavior characteristic of autism. The research offers a potential target for drugs to treat the condition.
Earlier research already has shown that the gene is defective in children with autism, but its effect on neurons in the brain was not known. The new studies in mice show that abnormal action of just this one gene disrupted energy use in neurons. The harmful changes were coupled with antisocial and prolonged repetitive behavior — traits found in autism.
The research is published online today in the scientific journal PLoS ONE.
"A number of genes and environmental factors have been shown to be involved in autism, but this study points to a mechanism — how one gene defect may trigger this type of neurological behavior," said study senior author Cecilia Giulivi, professor of molecular biosciences in the UC Davis School of Veterinary Medicine and a researcher affiliated with the UC Davis MIND Institute.
"Once you understand the mechanism, that opens the way for developing drugs to treat the condition," she said.
The defective gene appears to disrupt neurons’ use of energy, Giulivi said, the critical process that relies on the cell’s molecular energy factories called mitochondria.
In the research, a gene called pten was tweaked in the mice so that neurons lacked the normal amount of pten’s protein. The scientists detected malfunctioning mitochondria in the mice as early as 4 to 6 weeks after birth.
By 20 to 29 weeks, DNA damage in the mitochondria and disruption of their function had increased dramatically. At this time the mice began to avoid contact with their litter mates and engage in repetitive grooming behavior. Mice without the single gene change exhibited neither the mitochondria malfunctions nor the behavioral problems.
The antisocial behavior was most pronounced in the mice at an age comparable in humans to the early teenage years, when schizophrenia and other behavioral disorders become most apparent, Giulivi said.
The research showed that, when defective, pten’s protein interacts with the protein of a second gene known as p53 to dampen energy production in neurons. This severe stress leads to a spike in harmful mitochondrial DNA changes and abnormal levels of energy production in the cerebellum and hippocampus — brain regions critical for social behavior and cognition.
Pten mutations previously have been linked to Alzheimer’s disease as well as a spectrum of autism disorders. The new research shows that when pten protein was insufficient, its interaction with p53 triggered deficiencies and defects in other proteins that also have been found in patients with learning disabilities including autism.
Source: UCDavis
Research shows nerve stimulation can reorganize brain
July 19, 2012 By Emily Martinez
(Medical Xpress) — UT Dallas researchers recently demonstrated how nerve stimulation paired with specific experiences, such as movements or sounds, can reorganize the brain. This technology could lead to new treatments for stroke, tinnitus, autism and other disorders.
Dr. Michael Kilgard helped lead a team that paired vagus nerve stimulation with physical movement to improve brain function.
In a related paper, UT Dallas neuroscientists showed that they could alter the speed at which the brain works in laboratory animals by pairing stimulation of the vagus nerve with fast or slow sounds.
A team led by Dr. Robert Rennaker and Dr. Michael Kilgard looked at whether repeatedly pairing vagus nerve stimulation with a specific movement would change neural activity within the laboratory rats’ primary motor cortex. To test the hypothesis, they paired the vagus nerve stimulation with movements of the forelimb in two groups of rats. The results were published in a recent issue of Cerebral Cortex.
After five days of stimulation and movement pairing, the researchers examined the brain activity in response to the stimulation. The rats who received the training along with the stimulation displayed large changes in the organization of the brain’s movement control system. The animals receiving identical motor training without stimulation pairing did not exhibit any brain changes, or plasticity.
People who suffer strokes or brain trauma often undergo rehabilitation that includes repeated movement of the affected limb in an effort to regain motor skills. It is believed that repeated use of the affected limb causes reorganization of the brain essential to recovery. The recent study suggests that pairing vagus nerve stimulation with standard therapy may result in more rapid and extensive reorganization of the brain, offering the potential for speeding and improving recovery following stroke, said Rennaker, associate professor in The University of Texas at Dallas’ School of Behavioral and Brain Sciences.
“Our goal is to use the brain’s natural neuromodulatory systems to enhance the effectiveness of standard therapies,” Rennaker said. “Our studies in sensory and motor cortex suggest that the technique has the potential to enhance treatments for neurological conditions ranging from chronic pain to motor disorders. Future studies will investigate its effectiveness in treating cognitive impairments.”
New Evidence Links Immune Irregularities to Autism, Mouse Study Suggests
ScienceDaily (July 17, 2012) — Scientists at the California Institute of Technology (Caltech) pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder.
Scientists at Caltech pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder. (Credit: Elaine Hsiao)
What has remained unanswered, however, is whether the immune changes play a causative role in the development of the disease or are merely a side effect. Now a new Caltech study suggests that specific changes in an overactive immune system can indeed contribute to autism-like behaviors in mice, and that in some cases, this activation can be related to what a developing fetus experiences in the womb.
The results appear in a paper this week in the Proceedings of the National Academy of Sciences (PNAS).
"We have long suspected that the immune system plays a role in the development of autism spectrum disorder," says Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at Caltech, who led the work. "In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring."
The first step in the work was establishing a mouse model that tied the autism-related behaviors together with immune changes. Several large epidemiological studies — including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005 — have found a correlation between viral infection during the first trimester of a mother’s pregnancy and a higher risk for autism spectrum disorder in her child. To model this in mice, the researchers injected pregnant mothers with a viral mimic that triggered the same type of immune response a viral infection would.
"In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson’s lab and lead author of the PNAS paper.
The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder — repetitive or stereotyped behaviors, decreased social interactions, and impaired communication. In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.
Next, the researchers characterized the immune system of the offspring of mothers that had been infected and found that the offspring display a number of immune changes. Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a key role in suppressing the immune response. Taken together, the observed immune alterations add up to an immune system in overdrive — one that promotes inflammation.
"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. "This tells us that a prenatal challenge can result in long-term consequences for health and development."
With the mouse model established, the group was then able to test whether the offspring’s immune problems contribute to their autism-related behaviors. In the most revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like behavioral impairments.
The researchers emphasize that because the work was conducted in mice, the results cannot be readily extrapolated to humans, and they certainly do not suggest that bone-marrow transplants should be considered as a treatment for autism. They also have yet to establish whether it was the infusion of stem cells or the bone-marrow transplant procedure itself — complete with irradiation — that corrected the behaviors.
However, Patterson says, the results do suggest that immune irregularities in children could be an important target for innovative immune manipulations in addressing the behaviors associated with autism spectrum disorder. By correcting these immune problems, he says, it might be possible to ameliorate some of the classic developmental delays seen in autism.
In future studies, the researchers plan to examine the effects of highly targeted anti-inflammatory treatments on mice that display autism-related behaviors and immune changes. They are also interested in considering the gastrointestinal (GI) bacteria, or microbiota, of such mice. Coauthor Sarkis Mazmanian, a professor of biology at Caltech, has shown that gut bacteria are intimately tied to the function of the immune system. He and Patterson are investigating whether changes to the microbiota of these mice might also influence their autism-related behaviors.
Source: Science Daily
Questionnaire Completed by Parents May Help Identify One-Year-Olds at Risk for Autism
ScienceDaily (July 13, 2012) — A new study by University of North Carolina School of Medicine researchers found that 31 percent of children identified as at risk for autism spectrum disorders (ASD) at 12 months received a confirmed diagnosis of ASD by age 3 years.
In addition, 85 percent of the children found to be at risk for ASD based on results from the First Year Inventory (FYI), a 63-item questionnaire filled out by their parents, had some other developmental disability or concern by age three, said Grace Baranek, PhD, senior author of the study and an autism researcher with the Program for Early Autism, Research, Leadership and Service (PEARLS) in the Department of Allied Health Sciences at the UNC School of Medicine.
"These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention," she said.
Lead author of the study, Lauren Turner-Brown, PhD, also a researcher with PEARLS and the Carolina Institute for Developmental Disabilities said, “Identification of children at risk for ASD at 12 months could provide a substantial number of children and their families with access to intervention services months or years before they would otherwise receive a traditional diagnosis.”
The First Year Inventory was developed by Grace Baranek, PhD, Linda Watson, EdD, Elizabeth Crais, PhD and J. Steven Reznick, PhD, who are all researchers with PEARLS. All are also co-authors of the study with Turner-Brown, published online ahead of print on July 10, 2012 by Autism: The International Journal of Research & Practice.
In the study, parents of 699 children who had completed the FYI when their child was 12 months old completed additional screening questionnaires when their child reached age 3. In addition, children who were found to be at risk for ASD based on these measures were invited for in-person diagnostic evaluations.
"These findings are encouraging and suggest promise in the approach of using parent report of infant behaviors as a tool for identifying 12-month-olds who are at risk for an eventual diagnosis of ASD," Turner-Brown said.
Source: Science Daily