Posts tagged ASD
Posts tagged ASD
Difficulties in social interaction are considered to be one of the behavioral hallmarks of autism spectrum disorders (ASDs). Previous studies have shown these difficulties to be related to differences in how the brains of autistic individuals process sensory information about faces. Now, a group of researchers led by California Institute of Technology (Caltech) neuroscientist Ralph Adolphs has made the first recordings of the firings of single neurons in the brains of autistic individuals, and has found specific neurons in a region called the amygdala that show reduced processing of the eye region of faces. Furthermore, the study found that these same neurons responded more to mouths than did the neurons seen in the control-group individuals.
"We found that single brain cells in the amygdala of people with autism respond differently to faces in a way that explains many prior behavioral observations," says Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology at Caltech and coauthor of a study in the November 20 issue of Neuron that outlines the team’s findings. “We believe this shows that abnormal functioning in the amygdala is a reason that people with autism process faces abnormally.”
The amygdala has long been known to be important for the processing of emotional reactions. To make recordings from this part of the brain, Adolphs and lead author Ueli Rutishauser, assistant professor in the departments of neurosurgery and neurology at Cedars-Sinai Medical Center and visiting associate in biology at Caltech, teamed up with Adam Mamelak, professor of neurosurgery and director of functional neurosurgery at Cedars-Sinai, and neurosurgeon Ian Ross at Huntington Memorial Hospital in Pasadena, California, to recruit patients with epilepsy who had electrodes implanted in their medial temporal lobes—the area of the brain where the amygdala is located—to help identify the origin of their seizures. Epileptic seizures are caused by a burst of abnormal electric activity in the brain, which the electrodes are designed to detect. It turns out that epilepsy and ASD sometimes go together, and so the researchers were able to identify two of the epilepsy patients who also had a diagnosis of ASD.
By using the implanted electrodes to record the firings of individual neurons, the researchers were able to observe activity as participants looked at images of different facial regions, and then correlate the neuronal responses with the pictures. In the control group of epilepsy patients without autism, the neurons responded most strongly to the eye region of the face, whereas in the two ASD patients, the neurons responded most strongly to the mouth region. Moreover, the effect was present in only a specific subset of the neurons. In contrast, a different set of neurons showed the same response in both groups when whole faces were shown.
"It was surprising to find such clear abnormalities at the level of single cells," explains Rutishauser. "We, like many others, had thought that the neurological abnormalities that contribute to autism were spread throughout the brain, and that it would be difficult to find highly specific correlates. Not only did we find highly specific abnormalities in single-cell responses, but only a certain subset of cells responded that way, while another set showed typical responses to faces. This specificity of these cell populations was surprising and is, in a way, very good news, because it suggests the existence of specific mechanisms for autism that we can potentially trace back to their genetic and environmental causes, and that one could imagine manipulating for targeted treatment."
"We can now ask how these cells change their responses with treatments, how they correspond to similar cell populations in animal models of autism, and what genes this particular population of cells expresses," adds Adolphs.
To validate their results, the researchers hope to identify and test additional subjects, which is a challenge because it is very hard to find people with autism who also have epilepsy and who have been implanted with electrodes in the amygdala for single-cell recordings, says Adolphs.
"At the same time, we should think about how to change the responses of these neurons, and see if those modifications correlate with behavioral changes," he says.
The iPad you use to check email, watch episodes of Mad Men and play Words with Friends may hold the key to enabling children with autism spectrum disorders to express themselves through speech. New research indicates that children with autism who are minimally verbal can learn to speak later than previously thought, and iPads are playing an increasing role in making that happen, according to Ann Kaiser, a researcher at Vanderbilt Peabody College of education and human development.
In a study funded by Autism Speaks, Kaiser found that using speech-generating devices to encourage children ages 5 to 8 to develop speaking skills resulted in the subjects developing considerably more spoken words compared to other interventions. All of the children in the study learned new spoken words and several learned to produce short sentences as they moved through the training.
“For some parents, it was the first time they’d been able to converse with their children,” said Kaiser, Susan W. Gray Professor of Education and Human Development. “With the onset of iPads, that kind of communication may become possible for greater numbers of children with autism and their families.”
Augmentative and alternative communication devices—which employ symbols, gestures, pictures and speech output—have been used for decades by people who have difficulty speaking. Now, with the availability of apps that emulate those devices, the iPad offers a more accessible, cheaper and more user-friendly way to help minimally verbal children with autism to communicate. And, the iPad is far less stigmatizing for young people with autism who rely on them for communicating with fellow students, teachers and friends.
The reason speech-generating devices like the iPad are effective in promoting language development is simple. “When we say a word it sounds a little different every time, and words blend together and take on slightly different acoustic characteristics in different contexts,” Kaiser explained. “Every time the iPad says a word, it sounds exactly the same, which is important for children with autism, who generally need things to be as consistent as possible.”
As many as a third of children with autism have mastery of only a few words by the time they are school age. Previously, researchers thought that if children with autism had not begun to speak by age 5 or 6, they were unlikely to acquire spoken language. But Kaiser is encouraged by study results and believes that her iPad studies may help change that notion.
Building on findings from this research, Kaiser has begun a new five-year long study supported by the National Institutes of Health’s Autism Centers of Excellence with colleagues at UCLA, University of Rochester, and Cornell Weill Medical School. She and a team of researchers and therapists at the four sites are using iPads in two contrasting interventions (direct-teaching and naturalistic-teaching) to evaluate the effectiveness of the two communication interventions for children who have autism and use minimal spoken language.
In the direct-teaching approach, children are taught prerequisite skills for communication (such as matching objects, motor imitation and verbal imitation) and basic communication skills (such as requesting objects) in a massed trial format. For example, an adult partner may present five to 10 consecutive opportunities for a child to use the iPad to request preferred objects. During these opportunities, the child is prompted to use the iPad to request and may receive physical assistance if he cannot use the iPad independently.
In the naturalistic-teaching approach, the adult models the use of the iPad during play and conversation. She also teaches turn-taking, use of gestures to communicate, play with objects and social attention to partners during the play. She provides a limited number of prompts to use the iPad to make choices, to comment or make new requests.
In both approaches, children touch the symbols on the screen, listen to the device repeat the words, and sometimes say the words themselves. They are encouraged to use both words and the iPad to communicate, and the adult therapist uses both modes of communication throughout the instructional sessions.
Results from the Autism Speaks study will be available in Spring 2014; the NIH study will continue through Spring 2017; and more information can be found at Kidtalk.org.
The brains of children with autism show more connections than the brains of typically developing children do. What’s more, the brains of individuals with the most severe social symptoms are also the most hyper-connected. The findings reported in two independent studies published in the Cell Press journal Cell Reports (1, 2) on November 7th are challenge the prevailing notion in the field that autistic brains are lacking in neural connections.
The findings could lead to new treatment strategies and new ways to detect autism early, the researchers say. Autism spectrum disorder is a neurodevelopmental condition affecting nearly 1 in 88 children.
"Our study addresses one of the hottest open questions in autism research," said Kaustubh Supekar of Stanford University School of Medicine of his and his colleague Vinod Menon’s study aimed at characterizing whole-brain connectivity in children. "Using one of the largest and most heterogeneous pediatric functional neuroimaging datasets to date, we demonstrate that the brains of children with autism are hyper-connected in ways that are related to the severity of social impairment exhibited by these children."
In the second Cell Reports study, Ralph-Axel Müller and colleagues at San Diego State University focused specifically on neighboring brain regions to find an atypical increase in connections in adolescents with a diagnosis of autism spectrum disorder. That over-connection, which his team observed particularly in the regions of the brain that control vision, was also linked to symptom severity.
"Our findings support the special status of the visual system in children with heavier symptom load," Müller said, noting that all of the participants in his study were considered "high-functioning" with IQs above 70. He says measures of local connectivity in the cortex might be used as an aid to diagnosis, which today is based purely on behavioral criteria.
For Supekar and Menon, these new views of the autistic brain raise the intriguing possibility that epilepsy drugs might be used to treat autism.
"Our findings suggest that the imbalance of excitation and inhibition in the local brain circuits could engender cognitive and behavioral deficits observed in autism," Menon said. That imbalance is a hallmark of epilepsy as well, which might explain why children with autism so often suffer with epilepsy too.
"Drawing from these observations, it might not be too far fetched to speculate that the existing drugs used to treat epilepsy may be potentially useful in treating autism," Supekar said.
Researchers at Marcus Autism Center, Children’s Healthcare of Atlanta and Emory University School of Medicine have identified signs of autism present in the first months of life. The researchers followed babies from birth until 3 years of age, using eye-tracking technology, to measure the way infants look at and respond to social cues. Infants later diagnosed with autism showed declining attention to the eyes of other people, from the age of 2 months onwards. The results are reported in the Nov. 6, 2013 advanced online publication of the journal Nature.
The study followed two groups of infants, one at low and one at high risk for having autism spectrum disorders. High-risk infants had an older sibling already diagnosed with autism, increasing the infant’s risk of also having the condition by 20 fold. In contrast, low-risk infants had no first, second, or third degree relatives with autism.
"By following these babies from birth, and intensively within the first six months, we were able to collect large amounts of data long before overt symptoms are typically seen," said Warren Jones, Ph.D., the lead author on the study. Teams of clinicians assessed the children longitudinally and confirmed their diagnostic outcomes at age 3. Then the researchers analyzed data from the infants’ first months to identify what factors separated those who received an autism diagnosis from those who did not. What they found was surprising.
"We found a steady decline in attention to other people’s eyes, from 2 until 24 months, in infants later diagnosed with autism," said co-investigator Ami Klin, Ph.D., director of Marcus Autism Center. Differences were apparent even within the first 6 months, which has profound implications. "First, these results reveal that there are measurable and identifiable differences present already before 6 months. And second, we observed declining eye fixation over time, rather than an outright absence. Both these factors have the potential to dramatically shift the possibilities for future strategies of early intervention."
Jones is director of research at Marcus Autism Center and assistant professor in the Department of Pediatrics at Emory University School of Medicine. Klin is director of Marcus Autism Center, chief of the Division of Autism & Related Disorders in the Department of Pediatrics at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar.
The researchers caution that what they observed would not be visible to the naked eye, but requires specialized technology and repeated measurements of a child’s development over the course of months.
"To be sure, parents should not expect that this is something they could see without the aid of technology," said Jones, "and they shouldn’t be concerned if an infant doesn’t happen to look at their eyes at every moment. We used very specialized technology to measure developmental differences, accruing over time, in the way that infants watched very specific scenes of social interaction."
Before they can crawl or walk, babies explore the world intensively by looking at it, and they look at faces, bodies, and objects, as well as other people’s eyes. This exploration is a natural and necessary part of infant development, and it sets the stage for brain growth.
The critical implications of the study relate to what it reveals about the early development of social disability. Although the results indicate that attention to others’ eyes is already declining by 2 to 6 months in infants later diagnosed with autism, attention to others’ eyes does not appear to be entirely absent. If infants were identified at this early age, interventions could more successfully build on the levels of eye contact that are present. Eye contact plays a key role in social interaction and development, and in the study, those infants whose levels of eye contact diminished most rapidly were also those who were most disabled later in life. This early developmental difference also gives researchers a key insight for future studies.
"The genetics of autism have proven to be quite complex. Many hundreds of genes are likely to be involved, with each one playing a role in just a small fraction of cases, and contributing to risk in different ways in different individuals," said Jones. "The current results reveal one way in which that genetic diversity may be converted into disability very early in life. Our next step will be to expand these studies with more children, and to combine our eye-tracking measures with measures of gene expression and brain growth."
A novel autism intervention program using theatre to teach reciprocal communication skills is improving social deficits in adolescents with the disorder that now affects an estimated one in 88 children, Vanderbilt University researchers released today in the journal Autism Research.
The newly released study assessed the effectiveness of a two-week theatre camp on children with autism spectrum disorder and found significant improvements were made in social perception, social cognition and home living skills by the end of the camp. There were also positive changes in the participants’ physiological stress and reductions in self-reported parental stress.
Called SENSE Theatre, the Social Emotional Neuroscience & Endocrinology (SENSE) program evaluates the social functioning of children with autism and related neurodevelopmental disorders.
Camp participants ages 8 to 17 years join with typically developing peers who are specially trained to serve as models for social interaction and communication, skills that are difficult for children with autism. The camp uses techniques such as role-play and improvisation and culminates in public performances of a play.
“The findings show that treatment can be delivered in an unconventional setting, and children with autism can learn from unconventional ‘interventionists’ – their typically developing peer,” said lead author Blythe Corbett, Ph.D., associate professor of Psychiatry.
Social perception and interaction skills were measured before and after the camp using neuropsychological measures, play with peers and parental reporting. Significant differences were found in face processing, social awareness and social cognition, and duration of interaction with familiar peers increased significantly over the course of the camp.
Additionally, the stress hormone cortisol was measured through saliva samples taken both at home and throughout the camp to compare the stress level of participants at home, at the beginning of the camp and at the end of the camp. Cortisol levels rose on the first day of camp when compared to home values but declined by the end of treatment and during post-treatment play with peers.
“Our findings show that the SENSE Theatre program contributes to improvement in core social deficits when engaging with peers both on and off the stage,” Corbett said. “This research also shows it’s never too late to make a significant difference in the lives of children and youth with autism spectrum disorder, as [this program] targets children who are much older than kids who are participating in early intervention, yet we are still seeing significant gains in the core deficits of autism, and in a rather brief intervention.”
This research was supported by the Martin McCoy-Jesperson Discovery Grant in Positive Psychology and a grant from the National Institute of Mental Health (Grant No. R01 MH085717).
Corbett will continue using theatre techniques to study areas of social functioning among children with autism through a newly awarded grant from the National Institute of Mental Health (Grant No. R34 MH097793). This forthcoming study will explore treatment length and peer familiarity as factors in optimizing and generalizing gains and will enroll more than 30 youth with autism ages 8 to 16 in a 10-week program model beginning January 2014.
Video-based teaching helps teens with autism learn important social skills, and the method eventually could be used widely by schools with limited resources, a Michigan State University researcher says.
The diagnosis rate for Autism Spectrum Disorder for 14- to 17-year-olds has more than doubled in the past five years, according to the Centers for Disease Control and Prevention. Yet previous research has found very few strategies for helping adolescents with autism develop skills needed to be successful, especially in group settings.
“Teaching social skills to adolescents with ASD has to be effective and practical,” said Joshua Plavnick, assistant professor of special education at MSU. “Using video-based group instruction regularly could promote far-reaching gains for students with ASD across many social behaviors.”
Plavnick developed group video teaching techniques with colleagues while a postdoctoral fellow at the University of North Carolina’s Frank Porter Graham Child Development Institute. Their findings are published in the research journal Exceptional Children.
Previous studies have shown many people with autism are more likely to pay attention when an innovative technology delivers information. Before Plavnick’s work, however, there were no investigations of video modeling as an option for teaching social skills to more than one adolescent with ASD at the same time.
The team recruited 13- to 17-year-old students with ASD and used laptops or iPads to offer group video instruction on social behaviors, such as inviting a peer to join an activity. One facilitator showed four students video footage of people helping one another clean up a mess, for example, and then gave them opportunities to practice the same skills in the classroom.
According to the researchers, the students demonstrated a rapid increase in the level of complex social behaviors each time video-based group instruction was used. Students sustained those social behaviors at high levels, even when the videos were used less often.
The students’ parents also completed anonymous surveys and indicated high levels of satisfaction. One reported their child started asking family members to play games together, a skill the teen had never before displayed at home.
Most schools do not have appropriate staff resources to provide one-on-one help for students with autism. The video can be used with a small group all at once and has been shown to be effective.
“Video-based group instruction is important, given the often limited resources in schools that also face increasing numbers of students being diagnosed with ASD,” said Plavnick, who also has begun implementing the strategy as part of a daily high school-based program.
Findings in bacteria, yeast, mice show how flawed transport gene contributes to the condition
Researchers say it’s clear that some cases of autism are hereditary, but have struggled to draw direct links between the condition and particular genes. Now a team at the Johns Hopkins University School of Medicine, Tel Aviv University and Technion-Israel Institute of Technology has devised a process for connecting a suspect gene to its function in autism.
In a report in the Sept. 25 issue of Nature Communications, the scientists say mutations in one such autism-linked gene, dubbed NHE9, which is involved in transporting substances in and out of structures within the cell, causes communication problems among brain cells that likely contribute to autism.
“Autism is considered one of the most inheritable neurological disorders, but it is also the most complex,” says Rajini Rao, Ph.D., a professor of physiology in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine. “There are hundreds of candidate genes to sort through, and a single genetic variant may have different effects even within the same family. This makes it difficult to separate the chaff from the grain, to distinguish harmless variations from disease-causing mutations. We were able to use a new process to screen variants in one candidate gene that has been linked to autism, and figure out how they might contribute to the disorder.”
An estimated one in 88 children in the United States is affected by autism spectrum disorders, a group of neurological development conditions marked by varying degrees of social, communication and behavioral problems. Scientists for years have looked for the biological roots of the problem using tools such as genome-wide association studies and gene-linkage analysis, which crunch genetic and health data from thousands of people in an effort to pinpoint disease-causing genetic variants. But while such techniques have turned up a number of gene mutations that may be linked to autism, none of them appear in more than 1 percent of people with the condition. With numbers that low, researchers need a way to screen variants in order to make a definitive link, Rao says.
For the new study, Rao and her collaborators focused on NHE9, which other researchers had flagged as a suspect in attention-deficit hyperactivity disorder, addiction and epilepsy as well as autism spectrum disorders. The gene was already known to be involved in transporting hydrogen, sodium and potassium ions in and out of cellular compartments called endosomes, and the team wondered how this function might be related to neurological conditions.
Rao’s collaborators at Tel Aviv University and Technion-Israel Institute of Technology constructed a computer model of the NHE9 protein based on previous research on a distant relative in bacteria. They then used the model to predict how autism-linked variants in the NHE9 gene would affect the protein’s shape and function. Some of them were predicted to cause dramatic changes, while other changes appeared to be more subtle.
Rao’s team next tested how these variant forms of NHE9 would affect a relatively simple organism often used in genetic studies: yeast. “Using yeast to screen the function of variants was a quick, easy and inexpensive way of figuring out which were worth further study, and which we could ignore because they didn’t have any effect,” Rao says. To do that, the team engineered the yeast form of NHE9 to have the variants seen in autistic people.
For those mutations that did have a detectable effect on the yeast, the team moved on to a third and more challenging step, in mouse brains. They homed in on astrocytes, a type of brain cell that clears the signaling molecule glutamate out of the way after it has performed its job of delivering a message across a synapse between two nerve cells. Using lab-grown mouse astrocytes with variant forms of NHE9, the researchers found a change in the pH (acidity) inside cellular compartments called endosomes, which in turn altered the ability of cells to take up glutamate. Because endosomes are the vehicles that deliver cargo essential for communication between brain cells, changing their pH alters traffic to and from the cell surface, which could affect learning and memory, Rao says. “Elevated glutamate levels are known to trigger seizures, perhaps explaining why autistic patients with mutations in NHE9 and related genes also have seizures,” she notes.
Rao and her team hope that pinpointing the importance of this trafficking mechanism in autism spectrum disorders may lead to the development of new drugs for autism that alter endosomal pH. As the use of genomic data becomes increasingly commonplace in the future, the step-wise strategy devised by her team can be used to screen gene variants and identify at-risk patients, she says.
Activating a mother’s immune system during her pregnancy disrupts the development of neural cells in the brain of her offspring and damages the cells’ ability to transmit signals and communicate with one another, researchers with the UC Davis Center for Neuroscience and Department of Neurology have found. They said the finding suggests how maternal viral infection might increase the risk of having a child with autism spectrum disorder or schizophrenia.
The research, “MHCI Requires MEF2 Transcription Factors to Negatively Regulate Synapse Density during Development and in Disease,” is published in the Journal of Neuroscience.
The study’s senior author is Kimberley McAllister, professor in the Center for Neuroscience with appointments in the departments of Neurology and Neurobiology, Physiology and Behavior, and a researcher with the UC Davis MIND Institute.
“This is the first evidence that neurons in the developing brain of newborn offspring are altered by maternal immune activation,” McAllister said. “Until now, very little has been known about how maternal immune activation leads to autism spectrum disorder and schizophrenia-like pathophysiology and behaviors in the offspring.”
The study was conducted in mice and rats and compared the brains of the offspring of rodents whose immune systems had been activated and those of animals whose immune systems had not been activated. The pups of animals that were exposed to viral infection had much higher brain levels of immune molecules known as the major histocompatibility complex I (MHCI) molecules.
“This is the first evidence that MHCI levels on the surface of young cortical neurons in offspring are altered by maternal immune activation,” McAllister said.
The researchers found that the high MHCI levels impaired the ability of the neurons from the newborn mice’s brains to form synapses, the tiny gaps separating brain cells through which signals are transmitted. Earlier research has suggested that ASD and schizophrenia may be caused by changes in the development of connections in the brain, especially the cerebral cortex.
The researchers experimentally reduced MHCI to normal levels in neurons from offspring following maternal immune activation.
“Remarkably, synapse density returned to normal levels in those neurons,” McAllister said.
“These results indicate that maternal immune activation does indeed alter connectivity during prenatal development, causing a profound deficit in the ability of cortical neurons to form synapses that is caused by changes in levels of MHCI on the neurons,” she said.
MHCI did not work alone to limit the development of synapses. In a series of experiments, the UC Davis researchers determined that MHCI interacted with calcineurin and myocyte enhancer factor-2 (Mef2), a protein that is a critical determinant of neuronal specialization.
MHCI, calcineurin and Mef2 form a biological signaling pathway that had not been previously identified. McAllister’s team showed that in the offspring of the maternal immune activation mothers, this novel signaling pathway was much more active than it was in the offspring of non-MIA animals.
“This finding provides a potential mechanism linking maternal immune activation to disease-linked behaviors,” McAllister said.
It also is a mechanism that may help McAllister and other scientists to develop diagnostic tests and eventually therapies to improve the lives of individuals with these neurodevelopmental disorders.
A new study of the brain of a maths supremo supports Darwin’s belief that intellectual excellence is largely due to “zeal and hard work” rather than inherent ability.
University of Sussex neuroscientists took fMRI scans of champion ‘mental calculator’ Yusnier Viera during arithmetical tasks that were either familiar or unfamiliar to him and found that his brain did not behave in an extraordinary or unusual way.
The paper, published this week (23 September 2013) in PLOS ONE, provides scientific evidence that some calculation abilities are a matter of practice. Co-author Dr Natasha Sigala says: “This is a message of hope for all of us. Experts are made, not born.”
Cuban-born Yusnier holds world records for being able to name the days of the week for any dates of the past 400 years, giving his answer in less than a second. This is the kind of ability sometimes found in those with autism, although Yusnier is not on the autistic spectrum. Unlike those with autism or the related condition Asperger’s, he is able to explain exactly how he calculates his answers – and even teaches his system and has written books on the subject.
The study, carried out at the Clinical Imaging Sciences Centre on the University of Sussex campus, suggests that Yusnier has honed his ability to create short cuts to his answers by storing information in the middle part of the brain specialised for long-term working memory (the hippocampus and surrounding cortex). This type of memory helps us carry out tasks in our area of expertise with speed and efficiency.
Although the left side of his brain was activated during mathematical problems – which is normal for all brains – the scientists observed that something slightly different happened when Yusnier was presented with unfamiliar problems.
The scans showed marked connectivity of the anterior parts of the brain (prefrontal cortex), which are involved in decision making, during the unfamiliar calculations. This supports Yusnier’s report that he was building in an extra step to his mental processes to turn an unfamiliar problem into a familiar one. His answers to the unfamiliar questions had an 80 per cent degree of accuracy (compared with more than 90 per cent for familiar questions) and his responses were slightly slower.
Dr Sigala explains: “Although this kind of ability is seen among some people with autism, it is much rarer in those not on that spectrum. Brain scans of those with autism tend to show a variety of activity patterns, and autistic people are not able to explain how they reach their answer.
“With Yusnier, however, it is clear that his expertise is a result of long-term practice – and motivation.”
She adds: “It was beyond the scope of our paper to discuss the debate on deliberate practice vs. innate ability. But our study does not provide evidence for specific innate ability for mental calculations. As put by Charles Darwin to Francis Galton: ‘ […] I have always maintained that, excepting fools, men did not differ much in intellect, only in zeal and hard work; I still think this an eminently important difference.’”
UC Davis MIND Institute research finds rigorous evaluations are needed to accurately diagnose autism in children with 22q11.2 deletion syndrome
Children with a genetic disorder called 22q11.2 deletion syndrome, who frequently are believed to also have autism, often may be misidentified because the social impairments associated with their developmental delay may mimic the features of autism, a study by researchers with the UC Davis MIND Institute suggests.
The study is the first to examine autism in children with chromosome 22q11.2 deletion syndrome, in whom the prevalence of autism has been reported at between 20 and 50 percent, using rigorous gold-standard diagnostic criteria. The research found that none of the children with 22q11.2 deletion syndrome “met strict diagnostic criteria” for autism.
The researchers said the finding is important because treatments designed for children with autism, such as widely used discrete-trial training methods, may exacerbate the anxiety that is commonplace among the population.
Rather, evaluations should be performed to assess autism and guide the selection of appropriate therapies based on the children’s symptoms, such as language and communication delay, the researchers said. The study, “Social impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a different Endophenotype?” is published online today in Springer’s Journal of Autism and Developmental Disorders.
A high prevalence of autism spectrum disorder has been reported in children with 22q11.2 deletion syndrome – as high as 50 percent based on parent-report measures. Children diagnosed with 22q11.2 deletion syndrome – or 22q – may experience mild to severe cardiac anomalies, weakened immune systems and malformations of the head and neck and the roof of the mouth, or palate. They also experience developmental delay, with IQs in the borderline-to-low-average range. They characteristically experience significant anxiety and appear socially awkward.
“The results of our study show that of the children involved in our study no child actually met strict diagnostic criteria for an autism spectrum disorder,” said Kathleen Angkustsiri, study lead author and assistant professor of developmental-behavioral pediatrics at the MIND Institute.
“This is very important because the literature cites rates of anywhere from 20 to 50 percent of children with the disorder also have an autism spectrum disorder. Our findings lead us to question whether this is the correct label for these children who clearly have social impairments. We need to find out what interventions are most appropriate for their difficulties.”
The disorder’s name also describes its location on the 22nd chromosome as well as the nature of the genetic mutation, which is associated with a variety of anatomical and intellectual deficits. It has previously been known as Velocardiofacial Syndrome and Di George Syndrome, for the pediatric endocrinologist who described it in the 1960s.
The risk of 22q is about 1 in 2000 in the general population. The condition is seen in individuals of all backgrounds. Notably, people with 22q are at significantly heightened risk of developing mental-health disorders in adolescence and young adulthood. A person with 22q has a 30 times greater risk of developing schizophrenia than individuals in the general population.
“Because of the high rates of psychiatric disorders in childhood and adulthood, 22q is a very special population for prospective study looking at what’s happening throughout childhood that might either increase risk or provide protection against some of the later developing serious psychiatric illnesses, such as schizophrenia, that are associated with the disorder,” said Tony J. Simon, professor of psychiatry and behavioral sciences and director of the chromosome 22q11.2 deletion program at the MIND Institute.
The study was conducted among individuals recruited through the website of the Cognitive Analysis and Brain Imaging Laboratory (CABIL), which Simon directs. Simon and Angkustsiri said that the parents of children with 22q deletion syndrome often had commented that their children “seemed different” from other children with autism diagnoses, but that they hadn’t discovered a better diagnosis.
The clinical impression of the MIND Institute’s 22q deletion syndrome team, which includes psychologists Ingrid Leckliter and Janice Enriquez, was that the children were experiencing significant social impairments, but their presentation diverged from that of children with autism. To determine whether the children met the criteria for classic autism, they decided to test a subset of the children recruited from participants in a larger study of neurocognitive functioning, based on stringent methods and using multiple testing instruments.
The researchers selected 29 children –16 boys and 13 girls – for additional scrutiny, administering two tests. The Autism Diagnostic Observation Schedule (ADOS), a gold-standard assessment for autism, was administered to the children. The Social Communication Questionnaire (SCQ), a 40-question parent screening tool for communication and social functioning based on the gold-standard Autism Diagnostic Interview-Revised, was administered to their parents.
Typically, a diagnosis of autism spectrum disorder requires elevated scores on both a parent report measure, such as the SCQ, and a directly administered assessment such as the ADOS. Prior studies of autism in chromosome 22q11.2 deletion syndrome have only used parent report measures.
Only five of the 29 children had scores in the elevated range on the ADOS diagnostic tool. Four of the five had significant anxiety. Only two – 7 percent – had SCQ scores above the cut off. No child had both SCQ and ADOS scores in the relevant ranges that would lead to an ASD diagnosis.
“Over the years, a number of children came to us as part of the research or the clinical assessments that we perform, and their parents told us that they had an autism spectrum diagnosis. It’s quite clear that children with the disorder do have social impairments,” Simon said. “But it did seem to us that they did not have a classic case of autism spectrum disorder. They often have very high levels of social motivation. They get a lot of pleasure from social interaction, and they’re quite socially skilled.”
Simon said that the team also noted that the children’s social deficits might be more a function of their developmental delay and intellectual disability than autism.
“If you put them with their younger siblings’ friends they function very well in a social setting,” Simon continued, “and they interact well with an adult who accommodates their expectations for social interaction.”
Angkustsiri said that further study is needed to assess more appropriate treatments for children with 22q, such as improving their communication skills, treating their anxiety, helping them to remain focused and on task.
“There are a variety of different avenues that might be pursued rather than treatments that are designed to treat children with autism,” Angkustsiri said. “There are readily available, evidence-based treatments that may be more appropriate to help maximize these children’s potential.”