Playing Games That Infants Prefer Can Lessen Signs of Autism

Most people don’t like to be harassed, and babies with autism are no exception. While neurotypical infants often enjoy playing peek-a-boo, infants with autism spectrum disorders find it distressing. They’ll do their best to tune out all aspects of it, including the people playing with them.

Social disengagement is a hallmark of ASD and one of the characteristics that amplifies the disorder as infants develop into children and then adults.

Researchers at the Koegel Autism Center at UC Santa Barbara conducted a study that found that replacing such games in favor of those the infant prefers can actually lessen the severity of the infants’ ASD symptoms. They also make the astonishing claim that this could alleviate the condition altogether.

While it seems unlikely (to say the least) that playing the “right” game with a baby could drastically mitigate autism, it makes complete sense that playing a game the baby enjoys would be far more developmentally beneficial than playing one she hates. Is that really big news?

The study is in the current issue of the Journal of Positive Behavioral Interventions.

Lynn Koegel, clinical director of the center and the study’s lead author, described the game-playing protocol as a modified Pivotal Response Treatment (PVT). Developed at UCSB, PRT is based on principles of positive motivation. The researchers identified the activities that seemed to be more enjoyable to the infants and taught the respective parents to focus on those rather than on the typical games they might otherwise choose. “We had them play with their infants for short periods, and then give them some kind of social reward,” Koegel said. “Over time, we conditioned the infants to enjoy all the activities that were presented by pairing the less desired activities with the highly desired ones.” The social reward is preferable to, say, a toy, Koegel noted, because it maintains the ever-crucial personal interaction.

“The idea is to get them more interested in people,” she continued, “to focus on their socialization. If they’re avoiding people and avoiding interacting, that creates a whole host of other issues. They don’t form friendships, and then they don’t get the social feedback that comes from interacting with friends.”

According to Koegel, by the end of the relatively short one- to three-month intervention period, which included teaching the parents how to implement the procedures, all the infants in the study had normal reactions to stimuli. “Two of the three have no disabilities at all, and the third is very social,” she said. “The third does have a language delay, but that’s more manageable than some of the other issues.”

On a large scale, Koegel hopes to establish some benchmark for identifying social deficits in infants so parents and health care providers can intervene sooner rather than later. “We have a grant from the Autism Science Foundation to look at lots of babies and try to really figure out which signs are red flags, and which aren’t,” she said. “A number of the infants who show signs of autism will turn out to be perfectly fine; but we’re saying, let’s not take the risk if we can put an intervention in play that really works. Then we don’t have to worry about whether or not these kids would develop the full-blown symptoms of autism.”

Historically, ASD is diagnosed in children 18 months or older, and treatment generally begins around 4 years. “You can pretty reliably diagnose kids at 18 months, especially the more severe cases,” said Koegel. “The mild cases might be a little harder, especially if the child has some verbal communication. There are a few measures — like the ones we used in our study — that can diagnose kids pre-language, even as young as six months. But ours was the first that worked with children under 12 months and found an effective intervention.”

Given the increasing number of children being diagnosed with ASD, Koegel’s findings could be life altering — literally. “When you consider that the recommended intervention for preschoolers with autism is 30 to 40 hours per week of one-on-one therapy, this is a fairly easy fix,” she said. “We did a single one-hour session per week for four to 12 weeks until the symptoms improved, and some of these infants were only a few months old. We saw a lot of positive change.”

Share
Posted in Uncategorized | Leave a comment

Autism Spotted at Birth in Placentas

Intermediate trophoblast - intermed mag

This is what a trophoblast looks like under a microscope.
By Nephron (Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

Researchers at the Yale School of Medicine have figured out how to measure an infant’s risk of developing autism by looking for abnormalities in the placenta at birth. This method could allow for far earlier diagnosis and intervention. The findings are reported in the April 25 online issue of Biological Psychiatry.

One out of 50 children are diagnosed with an autism spectrum disorder in the United States each year, according to the Centers for Disease Control and Prevention (CDC), but the diagnosis is usually made when these children are 3 to 4 years of age or older. By then the best opportunities for intervention have been lost because the brain is most responsive to treatment in the first year of life.

Senior author Dr. Harvey Kliman, research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at the Yale School of Medicine, and research collaborators at the MIND Institute at the University of California, Davis, have found that abnormal placental folds and abnormal cell growths called trophoblast inclusions are key markers to identify newborns who are at risk for autism.

Kliman and his team examined 117 placentas from infants of at-risk families, those with one or more previous children with autism. These families were participating in a study called Markers of Autism Risk in Babies — Learning Early Signs. Kliman compared these at-risk placentas to 100 control placentas collected by the UC Davis researchers from the same geographic area.

The at-risk placentas had as many as 15 trophoblast inclusions, while none of the control placentas had more than two trophoblast inclusions. Kliman said a placenta with four or more trophoblast inclusions conservatively predicts an infant with a 96.7% probability of being at risk for autism.

Currently, the best early marker of autism risk is family history. Couples with a child with autism are nine times more likely to have another child with autism. Kliman said that when these at-risk families have subsequent children they could employ early intervention strategies to improve outcomes. “Regrettably couples without known genetic susceptibility must rely on identification of early signs or indicators that may not overtly manifest until the child’s second or third year of life,” said Kliman.

“I hope that diagnosing the risk of developing autism by examining the placenta at birth will become routine, and that the children who are shown to have increased numbers of trophoblast inclusions will have early interventions and an improved quality of life as a result of this test,” Kliman added.

Share
Posted in Uncategorized | Leave a comment

First Vaccine to Help Control Some Autism Symptoms

More than 90 percent of children with autism spectrum disorders have chronic, severe gastrointestinal symptoms. Of those, about 75 percent suffer from diarrhea, according to current literature.

That’s no fun.

But now, a first-of-its-kind vaccine, created by University of Guelph researchers, may help to alleviate this. The study by Brittany Pequegnat and Guelph chemistry professor Mario Monteiro appears this month in the journal Vaccine.

They developed a carbohydrate-based vaccine against the gut bug Clostridium bolteae, known to play a role in gastrointestinal disorders. It often shows up in higher numbers in the GI tracts of children with autism than in those of neurotypical kids.

“Little is known about the factors that predispose autistic children to C. bolteae,” said Monteiro. Although most infections are handled by some antibiotics, he said, a vaccine would improve current treatment.

“This is the first vaccine designed to control constipation and diarrhea caused by C. bolteae and perhaps control autism-related symptoms associated with this microbe,” he said.

Diagnosed cases of autism have increased almost sixfold over the past 20 years, and scientists don’t know all of the reasons for this. Although many experts point to changes in diagnostic procedures, access to diagnoses, and environmental factors, others have focused on the human gut.

Some researchers believe toxins and metabolites produced by gut bacteria, including C. bolteae, may be associated with symptoms and severity of autism, especially regressive autism.

Pequegnat, a master’s student, and Monteiro used bacteria grown by Mike Toh, a Guelph PhD student in the lab of microbiology professor Emma Allen-Vercoe.

The new anti- C. bolteae vaccine targets the specific complex polysaccharides, or carbohydrates, on the surface of the bug.

The vaccine effectively raised C. bolteae-specific antibodies in rabbits. Doctors could also use the vaccine-induced antibodies to quickly detect the bug in a clinical setting, said Monteiro.

The vaccine might take more than 10 years to work through preclinical and human trials, and it may take even longer before a drug is ready for market, Monteiro said.

“But this is a significant first step in the design of a multivalent vaccine against several autism-related gut bacteria,” he said.

Monteiro has studied sugar-based vaccines for two other gastric pathogens: Campylobacter jejuni, which causes travellers’ diarrhea, and Clostridium difficile, which causes antibiotic-associated diarrhea.

Share
Posted in Uncategorized | Tagged , , , , , , | Leave a comment

Epigenetic Changes Shed Light On Biological Mechanism of Autism

camera

Photo by the USDA

Scientists from King’s College London have identified patterns of epigenetic changes involved in autism spectrum disorder by studying genetically identical twins who differ in autism traits.

The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behavior traits.

ASD affects approximately 1 in 100 people in the UK and involves a spectrum of disorders that manifest differently in different people. People with ASD have varying levels of impairment across three common areas: deficits in social interactions and understanding, repetitive behavior and interests and impairments in language and communication development.

Evidence from twin studies shows there is a strong genetic component to ASD and previous studies suggest that genes that direct brain development may be involved in the disorder. In approximately 70 percent of cases, when one identical twin has ASD, so does the other. However, in 30 percent of cases, identical twins differ for ASD. Because identical twins share the same genetic code, this suggests non-genetic, or epigenetic, factors may be involved.

Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence — they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may provide targets for the development of new therapies.

The researchers studied an epigenetic mechanism called DNA methylation. DNA methylation acts to block the genetic sequences that drive gene expression, silencing gene activity. They examined DNA methylation at over 27,000 sites across the genome using samples taken from 50 identical twin pairs (100 individuals) from the UK Medical Research Council (MRC) funded Twins Early Development Study (TEDS): 34 pairs who differed for ASD or autism related behavior traits, 5 pairs where both twins have ASD, and 11 neurotypical twin pairs.

Dr Chloe Wong, first author of the study from King’s College London’s Institute of Psychiatry, says: “We’ve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder.”

DNA methylation at some genetic sites was consistently altered for all individuals with ASD, and differences at other sites were specific to certain symptom groups. The number of DNA methylation sites across the genome was also linked to the severity of autism symptoms suggesting a quantitative relationship between the two. Additionally, some of the differences in DNA methylation markers were located in genetic regions that previous research has associated with early brain development and ASD.

Professor Jonathan Mill, lead author of the paper from King’s College London’s Institute of Psychiatry and the University of Exeter, says: “Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions.”

Dr Alycia Halladay, Senior Director of Environmental and Clinical Sciences from Autism Speaks who funded the research, says: “This is the first large-scale study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical but have different symptoms. These findings open the door to future discoveries in the role of epigenetics — in addition to genetics — in the development of autism symptoms.”

Share
Posted in Uncategorized | Tagged , , , , , , | Leave a comment

Being Scientific about Language Acquisition

Mini pasta alphabet. Surprisingly challenging to assemble during breakfast.

Photo by Tama Leaver

Autistica, the UK’s leading autism research charity, published findings this month that found that 24 percent of children with autism do not speak or speak only minimally. We know that for some people with autism, lack of words can persist into adulthood.

Being able to communicate effectively is important. So is knowing the best ways to help people learn to communicate. Unfortunately, there are a lot of ineffective “treatments” out there.

Scientists at the University of Birmingham published a paper in Frontiers in Neuroscience showing that while not all of the current interventions used are effective, there is real hope for progress by using interventions based on understanding natural language development and the role of motor and “motor mirroring” behavior in toddlers.

The researchers, led by Dr Joe McCleery, who is supported by autism research charity Autistica, examined over 200 published papers and more than 60 different intervention studies, and found that:Motor behaviors, such as banging toys and copying gestures or facial expressions (“mirroring”), play a key role in the learning of language.

  • Children with autism show specific motor impairments, and less “mirroring” brain activity, particularly in relation to strangers in whom they show very little interest. This finding may hold the key to language problems overall.
  • Despite extensive use of sign language training to improve speech and communication skills in non-verbal children with autism, there is very little evidence that it makes a positive impact, potentially due to the impairments in motor behaviors and mirroring.
  • Picture exchange training can lead to improvements in speech. Here, children gradually learn to “ask” for things by exchanging pictures. This may work well because it does not depend on complex motor skills or mirroring.
  • Play-based approaches that employ explicit teaching strategies and are developmentally based are particularly successful.
  • New studies involving a focus on motor skills alongside speech and language intervention are showing promising preliminary results. This is exciting because these interventions use our new understanding of the role of motor behaviors in the development of speech and social interaction.

With the support of Autistica, Dr McCleery’s team have now embarked on new work which builds on these findings to design interventions that specifically target the aspects of development where there are deficits in non-verbal autistic children.

Dr McCleery says: “We feel that the field is approaching a turning point, with potentially dramatic breakthroughs to come in both our understanding of communication difficulties in people with autism, and the potential ways we can intervene to make a real difference for those children who are having difficulties learning to speak.”

Christine Swabey, CEO of Autistica, says: “80 percent of the parents in our recent consultation wanted interventions straight after diagnosis. Dr McCleery’s work shows how critical it is for all intervention to be evidence-based, and that the best approaches are based on a real understanding of the development of difficulties in autism. We are proud to be supporting the next steps in this vital research which will improve the quality of life for people with autism.”

Alison Hardy, whose son Alfie is 6, says: “As a parent of an autistic child, who is non-verbal, I feel quite vulnerable. People are always saying “try this, it worked wonders for us.” But you can’t try everything. We need a proper, scientific evidence base for what works and what does not. Then we can focus our time and our effort, with some confidence that we have a chance of helping our children. The publication of this research is an exciting step in giving us that confidence, it is great that Autistica is supporting this vital work.”

Share
Posted in Uncategorized | Tagged , , , , , , | Leave a comment

Brain Biology Tied to Social Reorientation During Entry to Adolescence

A specific region of the brain is in play when children consider their identity and social status as they transition into adolescence — that often-turbulent time of reaching puberty and entering middle school, says a University of Oregon psychologist.

In a study of 27 neurologically typical children who underwent functional magnetic resonance imaging (fMRI) at ages 10 and 13, activity in the brain’s ventromedial prefrontal cortex increased dramatically when the subjects responded to questions about how they view themselves.

The findings, published in the April 24 issue of the Journal of Neuroscience, confirm previous findings that specific brain networks support self-evaluations in the growing brain, but, more importantly, provide evidence that basic biology may well drive some of these changes, says Jennifer H. Pfeifer, professor of psychology and director of the psychology department’s Developmental Social Neuroscience Lab.

“This is a longitudinal fMRI study, which is still relatively uncommon,” Pfeifer said. “It suggests a link between neural responses during self-evaluative processing in the social domain, and pubertal development. This provides a rare piece of empirical evidence in humans, rather than animal models, that supports the common theory that adolescents are biologically driven to go through a social reorientation.”

Participants were scanned for about seven minutes at each visit. They responded to a series of attributes tied to social or academic domains — social ones such as “I am popular” or “I wish I had more friends” and academic ones such as “I like to read just for fun” or “Writing is so boring.” Social and academic evaluations were made about both the self and a familiar fictional character, Harry Potter.

In previous research, Pfeifer had found that a more dorsal region of the medial prefrontal cortex was more responsive in 10-year-old children during self-evaluations, when they were compared to adults. The new study, she said, provides a more detailed picture of how the brain supports self-development by looking at change within individuals.

The fMRI analyses found it was primarily the social self-evaluations that triggered significant increases over time in blood-oxygen levels, which fMRI detects, in the ventral medial prefrontal cortex. Additionally, these increases were strongest in children who experienced the most pubertal development over the three-year study period, for both girls and boys. Increases during academic self-evaluations were at best marginal. Whole-brain analyses found no other areas of the brain had significant increases or decreases in activity related to pubertal development.

“Neural changes in the social domain were more robust,” Pfeifer said. “Increased responses in this one region of the brain from age 10 to 13 were very evident in social self-evaluations, but not academic ones. This pattern is consistent with the enormous importance that most children entering adolescence place on their peer relationships and social status, compared to the relatively diminished value often associated with academics during this transition.”

In youth with autism spectrum disorders, this specialized response in ventral medial prefrontal cortex is missing, she added, citing a paper she co-wrote in the February 2013 issue of the Journal of Autism and Developmental Disorders and a complementary study led by Michael V. Lombardo, University of Cambridge, in the February 2010 issue of the journal Brain. The absence of this typical effect, Pfeifer said, might be related to the challenges kids with autism often face in both self-understanding and social relations.

“Dr. Pfeifer’s research examining self-evaluations during adolescence adds significantly to the intricate puzzle of this turbulent age period,” said Kimberly Andrews Espy, vice president for research and innovation and dean of the graduate school. “Researchers at the University of Oregon are piecing together how both biology and the environment dynamically and interactively support healthy social development.”

Share
Posted in Uncategorized | Tagged , , , , , | Leave a comment

Use of Seizure Drug During Pregnancy Associated With Increased Risk of Autism

Using a common drug for the treatment of epilepsy and other neuropsychological disorders during pregnancy was associated with a significantly increased risk of autism in offspring, according to a study in the April 24 issue of JAMA. The authors caution that these findings must be balanced against the treatment benefits for women who require the drug, valproate, to control epilepsy.

“Anti-epileptic drug exposure during pregnancy has been associated with an increased risk for congenital malformations and delayed cognitive development in the offspring, but little is known about the risk of other serious neuropsychiatric disorders,” according to background information in the article.

While only about 1 percent of the population is on the autism spectrum, nearly 4 percent of the population will develop epilepsy at some point.

Jakob Christensen, Ph.D., of Aarhus University Hospital, Aarhus, Denmark, and colleagues evaluated the association between maternal use of valproate during pregnancy and the risk of autism spectrum disorder and childhood autism in offspring. The population-based study included all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). Data were analyzed and adjusted for potential confounders (factors that can influence outcomes) such as maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity. Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.

The analysis included 655,615 children born from 1996 through 2006. The average age of the children at end of follow-up was 8.8 years. During the study period, 5,437 children were diagnosed with autism spectrum disorder, including 2,067 with childhood autism. The researchers identified 2,644 children exposed to antiepileptic drugs during pregnancy, including 508 exposed to valproate. The authors found that use of valproate during pregnancy was associated with an absolute risk of 4.42 percent for autism spectrum disorder and an absolute risk of 2.50 percent for childhood autism.

“In this population-based cohort study, children of women who used valproate during pregnancy had a higher risk of autism spectrum disorder and childhood autism compared with children of women who did not use valproate. Their risks were also higher than those for children of women who were previous users of valproate but who stopped before their pregnancy,” the researchers write.

“Because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance. Still, the absolute risk of autism spectrum disorder was less than 5 percent, which is important to take into account when counseling women about the use of valproate in pregnancy.”

Share
Posted in Uncategorized | Tagged , , , , , | Leave a comment

Friday Flick: What You Ought to Know about Autism

Nothing new here, at least not for our regular visitors, but pretty cute nonetheless.

Share
Posted in Uncategorized | Leave a comment

Brain Activity May Provide Objective Autism Indicator

CROSSED WIRES

Image via Flickr

We’ve written before about the problem of bias in diagnosing autism. That’s one reason why so many more boys than girls are diagnosed and why some regions — even some medical centers — diagnose so many more kids than others. Smart, patient, observant and understanding physicians are key, obviously, but a more objective first criterion would sure be helpful.

And now we may have found one.

Neuroscientists from Case Western Reserve University School of Medicine and the University of Toronto have developed an efficient and reliable method of analyzing brain activity to detect autism in children. Their findings appear today in the online journal PLOS ONE.

From the press release:

The researchers recorded and analyzed dynamic patterns of brain activity with magnetoencephalography (MEG) to determine the brain’s functional connectivity — that is, its communication from one region to another. MEG measures magnetic fields generated by electrical currents in neurons of the brain.

Roberto Fernández Galán, PhD, an assistant professor of neurosciences at Case Western Reserve and an electrophysiologist seasoned in theoretical physics led the research team that detected autism spectrum disorder (ASD) with 94 percent accuracy. The new analytic method offers an efficient, quantitative way of confirming a clinical diagnosis of autism.

“We asked the question, ‘Can you distinguish an autistic brain from a non-autistic brain simply by looking at the patterns of neural activity?’ and indeed, you can,” Galán said. “This discovery opens the door to quantitative tools that complement the existing diagnostic tools for autism based on behavioral tests.”

In a study of 19 children — nine with ASD — 141 sensors tracked the activity of each child’s cortex. The sensors recorded how different regions interacted with each other while at rest, and compared the brain’s interactions of the control group to those with ASD. Researchers found significantly stronger connections between rear and frontal areas of the brain in the ASD group; there was an asymmetrical flow of information to the frontal region, but not vice versa.

The new insight into the directionality of the connections may help identify anatomical abnormalities in ASD brains. Most current measures of functional connectivity do not indicate the interactions’ directionality.

“It is not just who is connected to whom, but rather who is driving whom,” Galán said.

Their approach also allows them to measure background noise, or the spontaneous input driving the brain’s activity while at rest. A spatial map of these inputs demonstrated there was more complexity and structure in the control group than the ASD group, which had less variety and intricacy. This feature offered better discrimination between the two groups, providing an even stronger measure of criteria than functional connectivity alone, with 94 percent accuracy.

Case Western Reserve’s Office of Technology Transfer has filed a provisional patent application for the analysis’ algorithm, which investigates the brain’s activity at rest. Galán and colleagues hope to collaborate with others in the autism field with emphasis on translational and clinical research.

Share
Posted in Uncategorized | Tagged , , , , | Leave a comment

For People with Autism, Propranolol May Improve Memory Even as it Curbs Panic

People on the autism spectrum often have trouble communicating and interacting with others because they process language, facial expressions and social cues differently than neurotypical people.

Researchers had previously found that propranolol, a drug commonly used to treat high blood pressure and anxiety and panic disorders, could improve the language and social abilities of people with ASDs. Now, University of Missouri investigators say the prescription drug could also help improve the working memory abilities of people with autism.

The study, “Noradrenergic Moderation of Working Memory Impairments in Adults with Autism Spectrum Disorder,” was published in the Journal of the International Neuropsychological Society. The press release is here.

Working memory referrs to a person’s ability to hold and manipulate a small amount of information for a short period; it’s what allows you to remember directions, complete puzzles and follow conversations. Neurologist David Beversdorf and research neuropsychologist Shawn Christ found that propranolol improves the working memory performance of people with ASDs.

“Seeing a tiger might signal a fight or flight response. Nowadays, a stressor such as taking an exam could generate the same response, which is not helpful,” said Beversdorf, an associate professor in the Departments of Radiology and Neurology in the MU School of Medicine. “Propranolol works by calming those nervous responses, which is why some people benefit from taking the drug to reduce anxiety.”

Propranolol increased working memory performance in a sample of 14 young adult patients of the MU Thompson Center for Autism and Neurodevelopmental Disorders but had little to no effect on a group of 13 study participants who do not have autism. The researchers do not recommend that doctors prescribe propranolol solely to improve working memory in individuals with an ASD, but patients who already take the prescription drug might benefit.

“People with an Autism Spectrum Disorder who are already being prescribed propranolol for a different reason, such as anxiety, might also see an improvement in working memory,” said Christ, an associate professor in the Department of Psychological Sciences in the MU College of Arts and Science.

Future research will incorporate clinical trials to assess further the relationship between cognitive and behavioral functioning and connectivity among various regions of the brain.

Share
Posted in Uncategorized | Tagged , , , , , , , , | Leave a comment