Posts tagged ASD
Posts tagged ASD
In the first successful experiment with humans using a treatment known as sensory-motor or environmental enrichment, researchers documented marked improvement in young autistic boys when compared to boys treated with traditional behavioral therapies, according to research published by the American Psychological Association.
The rationale for the new treatment is rooted in the fact that autistic children typically have sensory problems, the most common involving smell and touch sensitivity. Building on decades of work in animals documenting the profound effects of environmental enrichment on behavioral and neurological outcomes, the authors of the study predicted that similar enrichment in autistic children would have beneficial effects.
“Because parents can give their child sensory enrichment using items typically available in their home, this therapy provides a low-cost option for enhancing their child’s progress,” said study co-author Cynthia C. Woo, PhD, a project scientist at the University of California Irvine.
The study, which was published online in the APA journal Behavioral Neuroscience, involved 28 autistic boys, ages 3 to 12. Researchers placed the boys in two groups based on their age and autism severity. For six months, both groups participated in standard behavioral therapy but boys in one of the groups also underwent daily environmental enrichment exercises.
Parents of each of the 13 boys in the enrichment group received a kit that contained essential oil fragrances such as apple, lavender, lemon and vanilla to stimulate sense of smell. For touch, the kit contained squares of plastic doormat, smooth foam, a rubber sink mat, aluminum, fine sandpaper, felt and sponges. The kit also included pieces of carpet, hard flooring, pillows, cardboard and bubble wrap that parents laid on the floor to create a multi-textured walking path. Items for the children to manipulate included a piggy bank with plastic coins, miniature plastic fruits and a small fishing pole with a magnetic hook. Many household items were also used, such as bowls for holding water at different temperatures for the child to dip in a hand or foot and metal spoons that parents would warm or cool and touch to the child’s skin.
Researchers instructed the parents of children in the enrichment group to conduct two sessions a day of four to seven exercises involving different combinations of sensory stimuli for touch, temperature, sight and movement. Each session took 15 to 30 minutes to complete. The children also listened to classical music once a day.
Following six months of therapy, 42 percent of the children in the enrichment group significantly improved in behaviors such as relating to people and responding to sights and sounds, compared to 7 percent of the standard care group, according to the study. The children in the enrichment group also improved on scores for cognitive function, which covers aspects of perception and reasoning, whereas the average scores for the children in the standard care group decreased. In addition, 69 percent of parents in the enrichment group reported improvement in their child’s overall autism symptoms, compared to 31 percent of parents of the standard care group, the authors wrote.
“Sensory enrichment may well be an effective therapy for the treatment of autism, particularly in children much past the toddler stage,” said study co-author Michael Leon, PhD, a professor of neurobiology and behavior with the University of California Irvine.
“This is an exciting study for several reasons,” said Mark Blumberg, PhD, editor of Behavioral Neuroscience. “It is well designed, it builds on established findings from numerous experiments using non-human animals and it addresses the critical need to find effective treatments for autism. The obvious next step has to be replication of these results in a larger-scale study.”
Before the experiment, most of the children in both groups were undergoing the standard treatment for autism, applied behavior analysis, which typically involves 25 to 40 hours a week with a trained professional for a number of years, the study said. Some children in both groups were also undergoing speech therapy, social skills therapy, physical therapy for fine motor skills or occupational therapy with different types of exercises. Most current therapies for autism must be started at a very young age to be effective, whereas environmental enrichment worked for boys at least to age 12, the study said.
The researchers are now conducting a larger randomized clinical trial that includes girls. Another important next step will be to test environmental enrichment therapy when a child is not also receiving other standard treatments, the authors noted.
Using a kid-friendly robot during behavioral therapy sessions may help some children with autism gain better social skills, a preliminary study suggests.
The study, of 19 children with autism spectrum disorders (ASDs), found that kids tended to do better when their visit with a therapist included a robot “co-therapist.” On average, they made bigger gains in social skills such as asking “appropriate” questions, answering questions and making conversational comments.
So-called humanoid robots are already being marketed for this purpose, but there has been little research to back it up.
“Going into this study, we were skeptical,” said lead researcher Joshua Diehl, an assistant professor of psychology at the University of Notre Dame in Indiana, who said he has no financial interest in the technology.
“We found that, to our surprise, the kids did better when the robot was added,” he said.
There are still plenty of caveats, however, said Diehl, who is presenting his team’s findings Saturday at the International Meeting for Autism Research (IMFAR) in San Sebastian, Spain.
For one, the study was small. And it’s not clear that the results seen in a controlled research setting would be the same in the real world of therapists’ offices, according to Diehl.
“I’d say this is not yet ready for prime time,” he said.
ASDs are a group of developmental disorders that affect a person’s ability to communicate and interact socially. The severity of those effects range widely: Some people have mild problems socializing, but have normal to above-normal intelligence; some people have profound difficulties relating to others, and may have intellectual impairment as well.
Experts have become interested in using technology — from robots to iPads — along with standard ASD therapies because it may help bridge some of the communication issues kids have.
Human communication is complex and unpredictable, with body language, facial expressions and other subtle cues coming into the mix, explained Geraldine Dawson, chief science officer for the advocacy group Autism Speaks.
A robot or a computer game, on the other hand, can be programmed to be simple and predictable, and that may help kids with ASDs better process the information they are being given, Dawson said.
“Broadly speaking,” she said, “we are very excited about the potential role for technology in diagnosing and treating ASDs.” But she also agreed with Diehl that the findings are “very preliminary,” and that researchers have a lot more to learn about how technology — robots or otherwise — fits into ASD therapies.
For the study, Diehl’s team used a humanoid robot manufactured by Aldebaran Robotics, which markets the NAO robot for use in education, including special education for kids with ASDs. The robot, which stands at about 2 feet tall, looks like a toy but it’s priced more like a small car, Diehl noted.
The NAO H25 “Academic Edition” rings up at about $16,000. (Diehl said the study was funded by government and private grants, not the manufacturer.)
The researchers had 19 kids aged 6 to 13 complete 12 behavioral therapy sessions, where a therapist worked with the child on social skills. Half of the sessions involved the robot, named Kelly, which was wheeled out so the child could practice conversing with her, while the therapist stood by.
“So the child might say, ‘Hi Kelly, how are you?’” Diehl explained. “Then Kelly would say, ‘Fine. What did you do today?’” During the non-Kelly sessions, another person entered the room and carried on the same conversation with the child that the robot would have.
On average, Diehl’s team found, kids made bigger gains from the sessions that included Kelly — based on both their interactions with their therapists, and their parents’ reports.
“There was one child who, when his dad came home from work, asked him how his day was,” Diehl said. “He’d never done that before.”
Still, he stressed that while the robot sessions seemed more successful on average, the children varied widely in their responses to Kelly. Going forward, Diehl said, it will be important to figure out whether there are certain kids with ASDs more likely to benefit from a robot co-therapist.
Dawson agreed that there is no one-size-fits-all ASD therapy. “Any therapy for a person with an ASD has to be individualized,” she said. The idea with any technology, she added, is to give therapists and doctors extra “tools” to work with.
A separate study presented at the same meeting looked at another type of tool. Researchers had 60 “minimally verbal” children with ASDs attend two “play-based” sessions per week, aimed at boosting their ability to speak and gesture. Half of the kids were also given a “speech-generating device,” like an iPad.
Three and six months later, children who worked with the devices were able to say more words and were quicker to take up conversational skills.
Dawson said the robot and iPad studies are just part of the growing body of research into how technology can not only aid in ASD therapies, but also help doctors diagnose the disorders or help parents manage at home.
But both Diehl and Dawson stressed that no robot or iPad is intended to stand in for human connection. The idea, after all, is to enhance kids’ ability to communicate and have relationships, Dawson noted. “Technology will never take the place of people,” she said.
The data and conclusions of research presented at meetings should be viewed as preliminary until published in a peer-reviewed journal.
Most infants respond to a game of peek-a-boo with smiles at the very least, and, for those who find the activity particularly entertaining, gales of laughter. For infants with autism spectrum disorders (ASD), however, the game can be distressing rather than pleasant, and they’ll do their best to tune out all aspects of it –– and that includes the people playing with them.
That disengagement is a hallmark of ASD, and one of the characteristics that amplifies the disorder as infants develop into children and then adults.
A study conducted by researchers at the Koegel Autism Center at UC Santa Barbara has found that replacing such games in favor of those the infant prefers can actually lessen the severity of the infants’ ASD symptoms, and, perhaps, alleviate the condition altogether. Their work is highlighted the current issue of the Journal of Positive Behavior 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.”
Scientists from King’s College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) 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 behaviour traits.
ASD affects approximately 1 in 100 people in the UK and involves a spectrum of disorders which manifest themselves differently in different people. People with ASD have varying levels of impairment across three common areas: deficits in social interactions and understanding, repetitive behaviour 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% of cases, when one identical twin has ASD, so does the other. However, in 30% 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 therefore 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 behaviour traits, 5 pairs where both twins have ASD, and 11 healthy 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.”
We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n = 9) with Asperger’s syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n = 10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype.
Kids and teenagers suffering from autism spectrum disorder (ASD) are more likely to use television and video games and less likely to spend time on social media than their normally-developing counterparts, claims new research set for publication in a future issue of the Journal of Autism and Developmental Disorders.
Micah Mazurek, an assistant professor of health psychology and a clinical child psychologist at the University of Missouri, recruited 202 children and adolescents with ASD and 179 of their typically developing siblings for the study.
Those with ASD spent more time playing video games and watching TV than spending time on physical or pro-social activities (including spending time on websites like Facebook or Twitter). The opposite was also true: typically-developing children spent more time on non-screen-related activities than they did watching shows or playing on the PS3 or the Xbox 360, according to the soon-to-be-published study.
“Many parents and clinicians have noticed that children with ASD are fascinated with technology, and the results of our recent studies certainly support this idea,” Mazurek said in a statement. “We found that children with ASD spent much more time playing video games than typically developing children, and they are much more likely to develop problematic or addictive patterns of video game play.”
In a separate study of 169 boys with ASD, excessive video game use had been linked to oppositional behaviors, such as refusal to follow directions or getting into arguments with others. Mazurek said that the issues will need to be further examined in future, closely-controlled research.
“Because these studies were cross-sectional, it is not clear if there is a causal relationship between video game use and problem behaviors,” she said. “Children with ASD may be attracted to video games because they can be rewarding, visually engaging and do not require face-to-face communication or social interaction. Parents need to be aware that, although video games are especially reinforcing for children with ASD, children with ASD may have problems disengaging from these games.”
Despite those issues, Mazurek also believes that autistic children’s love for video games and television could be used for beneficial purposes. The professor believes that discovering what makes these screen-related pastimes so attractive to kids with ASD could help researchers and medical experts develop new treatment options.
“Using screen-based technologies, communication and social skills could be taught and reinforced right away,” Mazurek explained. “However, more research is needed to determine whether the skills children with ASD might learn in virtual reality environments would translate into actual social interactions.”
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.
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.
People with an Autism Spectrum Disorder (ASD) often have trouble communicating and interacting with others because they process language, facial expressions and social cues differently. Previously, researchers found that propranolol, a drug commonly used to treat high blood pressure, anxiety and panic, could improve the language abilities and social functioning of people with an ASD. Now, University of Missouri investigators say the prescription drug also could help improve the working memory abilities of individuals with autism.
Working memory represents individuals’ ability to hold and manipulate a small amount of information for a short period; it allows people 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 an ASD.
“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.
The study, “Noradrenergic Moderation of Working Memory Impairments in Adults with Autism Spectrum Disorder,” was published in the Journal of the International Neuropsychological Society. Kimberly Bodner, a psychological sciences doctoral student at MU, and Sanjida Saklayen from the Ohio State University College of Medicine co-authored the study.
The age at which a child with autism is diagnosed is related to the particular suite of behavioral symptoms he or she exhibits, new research from the University of Wisconsin-Madison shows.
Certain diagnostic features, including poor nonverbal communication and repetitive behaviors, were associated with earlier identification of an autism spectrum disorder, according to a study in the April issue of the Journal of the American Academy of Child and Adolescent Psychiatry. Displaying more behavioral features was also associated with earlier diagnosis.
“Early diagnosis is one of the major public health goals related to autism,” says lead study author Matthew Maenner, a researcher at the UW-Madison Waisman Center. “The earlier you can identify that a child might be having problems, the sooner they can receive support to help them succeed and reach their potential.”
But there is a large gap between current research and what is actually happening in schools and communities, Maenner adds. Although research suggests autism can be reliably diagnosed by age 2, the new analysis shows that fewer than half of children with autism are identified in their communities by age 5.
One challenge is that autism spectrum disorders (ASD) are extremely diverse. According to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR), the standard handbook used for classification of psychiatric disorders, there are more than 600 different symptom combinations that meet the minimum criteria for diagnosing autistic disorder, one subtype of ASD.
Previous research on age at diagnosis has focused on external factors such as gender, socioeconomic status, and intellectual disability. Maenner and his colleagues instead looked at patterns of the 12 behavioral features used to diagnose autism according to the DSM-IV-TR.
He and Maureen Durkin, a UW-Madison professor of population health and pediatrics and Waisman Center investigator, studied records of 2,757 8-year- olds from 11 surveillance sites in the nationwide Autism and Developmental Disabilities Monitoring Network, run by the Centers for Disease Control and Prevention (CDC). They found significant associations between the presence of certain behavioral features and age at diagnosis.
“When it comes to the timing of autism identification, the symptoms actually matter quite a bit,” Maenner says.
In the study population, the median age at diagnosis (the age by which half the children were diagnosed) was 8.2 years for children with only seven of the listed behavioral features but dropped to just 3.8 years for children with all 12 of the symptoms.
The specific symptoms present also emerged as an important factor. Children with impairments in nonverbal communication, imaginary play, repetitive motor behaviors, and inflexibility in routines were more likely to be diagnosed at a younger age, while those with deficits in conversational ability, idiosyncratic speech and relating to peers were more likely to be diagnosed at a later age.
These patterns make a lot of sense, Maenner says, since they involve behaviors that may arise at different developmental times. The findings suggest that children who show fewer behavioral features or whose autism is characterized by symptoms typically identified at later ages may face more barriers to early diagnosis.
But they also indicate that more screening may not always lead to early diagnoses for everyone.
“Increasing the intensity of screening for autism might lead to identifying more children earlier, but it could also catch a lot of people at later ages who might not have otherwise been identified as having autism,” Maenner says.
Children with autism have increased levels of genetic change in regions of the genome prone to DNA rearrangements, so called “hotspots,” according to a research discovery to be published in the print edition of the journal Human Molecular Genetics. The research indicates that these genetic changes come in the form of an excess of duplicated DNA segments in hotspot regions and may affect the chances that a child will develop autism — a behavioral disorder that affects about 1 of every 88 children in the United States, according to the Centers for Disease Control.
Earlier work had identified, in children with autism, a greater frequency of rare DNA deletions or duplications, known as DNA copy number changes. These rare and harmful events are found in approximately 5 to 10 percent of cases, raising the question as to what other genetic changes might contribute to the disorders known as autism spectrum disorders.
The new research shows that children with autism have — in addition to these rare events — an excess of duplicated DNA including more common variants not exclusively found in children with autism, but are found at elevated levels compared to typically developing children. The research collaboration includes groups led at Penn State by Scott Selleck; at the University of California Davis/MIND Institute by Isaac Pessah, Irva Hertz-Picciotto, Flora Tassone, and Robin Hansen; and at the University of Washington by Evan Eichler.
The investigators also found that the balance of DNA duplications and deletions in children with autism was different from that found in more severe developmental disorders, such as intellectual disability or multiple congenital anomalies, where the levels of both deletions and duplications are increased compared to controls, and are even higher than in children with autism.
They also found that children who had more difficulty with daily living skills also had the greatest level of copy number change throughout their genome. “These measures of adaptive behavior provide an indication of the severity of the impairment in the children with autism. These behaviors were significantly correlated with the amount of DNA copy number change,” Selleck said, emphasizing that the research revealed “clear and graded effects of the genetic change.”
“These results beg the question as to the origin of this genetic change,” Selleck said. “The increased levels of both rare and common variants suggests the possibility that these individuals are predisposed to genetic alteration.”
A vigorous debate is ongoing in the research community about the degree of genetic versus environmental contributions to autism. Selleck said the finding of an overall increase in genetic change in children with autism heightens the need to search for the basis of this variation. “We know that environmental factors can affect the stability of the genome, but we don’t know if the DNA copy number change we detect in these children is a result of environmental exposures, nutrition, medical factors, lifestyle, genetic susceptibility, or combinations of many elements together,” Selleck said. “The elevated levels of common variants is telling us something. It suggests that pure selection of randomly generated variants may not be the whole story.”
The Penn State team includes Department of Biochemistry and Molecular Biology Associate Professor Marylyn Ritchie and Assistant Professor Santhosh Girirajan. “The relationship between the level of copy number change and the degree of neurodevelopmental disability is something we have noted previously for large, rare variants” says Girirajan, “but this work extends those observations to common copy number variants, suggesting the level of copy number change in children with autism is larger than we had appreciated.” Girirajan, the first author of the study, coordinated the effort between the Penn State and University of Washington researchers.