Joint Chinese-UK study shows Levels similar to the West
The first large-scale study of autism in China has revealed that around one in a hundred people in the country has an autism spectrum condition – the same figure as found in the West.
The research was carried out by an international team of researchers from the University of Cambridge, UK, and the China Disabled Persons’ Federation and Chinese University of Hong Kong. It is the result of an international partnership launched in 2013.
Autism spectrum conditions – which include autism and Asperger’s syndrome – are characterised by impairments in social interaction and communication, alongside the presence of unusually repetitive behaviour and narrow interests, difficulties adjusting to unexpected change, and sensory hyper-sensitivity.
Autism was first described in Western cultures, and only later recognised in Asian countries. Around one in 100 school age children in the UK is autistic, but autism prevalence in China has been reported to be lower than in the West. The reasons for this difference are that most studies in China have only included the special school population, overlooking the mainstream school population; and that most studies in China have not used validated and reliable screening and diagnostic methods.
“Understanding the prevalence of autism is important because of its relevance to planning services to support those living with the condition, as well as their families,” said Professor Carol Brayne from the Cambridge Institute of Public Health.
Professor Simon Baron-Cohen, Director of the Autism Research Centre in Cambridge (ARC) added: “We need to study autism outside Western populations, since most of the research to date has only been carried out in the West. This collaboration with colleagues in China is so valuable to help us understand what is universal and what is culture-specific in autism research.”
To address the gap in understanding autism in China, the researchers tested the total autism prevalence in mainstream and special schools in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. They screened children aged 6 to 10?years old in the three cities using the Childhood Autism Screening Test (or CAST), a 37-item questionnaire, completed by parents, and developed and validated by the Cambridge team. The questionnaire gives a score of 0 to 31, and children scoring 15 or above were then given a clinical assessment. The results are published in the journal Molecular Autism.
In Jilin City, from a total population of 7,258, the team identified 77 cases of autism, equating to a prevalence of 108 per 10,000, very similar to that found in the West.
In Shenzhen and Jiamusi cities, only data for children in mainstream education was available; in Shenzhen City, 42 out of every 10,000 children in mainstream education had autism, and in Jiamusi City this figure was 19 per 10,000. In all three cities, the researchers identified new cases of autism in mainstream schools, confirming that there is under-diagnosis of autism in China.
“Contrary to previous studies, we have shown that the prevalence of autism spectrum conditions in China is in line with that found in the West,” said Dr Sophia Xiang Sun, who conducted this study as part of her PhD at Cambridge University and who is now based in the Star Kay Bridge Research Centre for Children with Autism in Xiamen, China.
Professor Patrick Leung, from the Chinese University of Hong Kong, said: “Previous research into the autism spectrum in China has mainly focused on the most severe subtype, childhood autism. We have been able to use a standardised screening methodology, allowing us to compare the results with Western countries to show that autism occurs broadly at the same rate, irrespective of culture.”
Dr Carrie Allison, from the Cambridge Autism Research Centre, commented: “Completing this study with colleagues in China has been nothing short of remarkable. It has involved translating Western autism screening instruments into Chinese, training Chinese clinicians in autism diagnosis, and working with national Chinese agencies, screening in three Chinese cities.”
Professor Fiona Matthews, the statistician on the Cambridge team and now based in Newcastle University, noted: “A strength of this study is the near universal response rate that is possible in China, which we rarely achieve in the West, making the epidemiology far more representative.”
The research was funded by the Autism Research Trust, the NIHR CLAHRC for East of England, the Chinese University of Hong Kong (CUHK), and the Medical Research Council UK.
Texas strategy reduces prescriptions without compromising care, Rutgers study finds
Rutgers researchers have found that a Texas strategy to reduce anti-psychotic medication for children can serve as a model for other state Medicaid programs.
The study was published in the Journal of the American Academy of Child & Adolescent Psychiatry.
“Youth in the United States foster care system are about five times more likely to take antipsychotic medications, a class of medications to manage their mental and behavioral health, than children in the general public,” said Thomas Mackie, assistant professor at Rutgers School of Public Health. In response, over 31 state Medicaid programs nationally are experimenting with different oversight strategies to ensure safe and judicious use of antipsychotic medications. These Medicaid programs are challenged to address these concerns while also ensuring access to antipsychotic medications in cases where these medications are clinically optimal, especially for those youth with psychosis, autism and other U.S. Food and Drug Administration–approved clinical indications.
An antipsychotic medication oversight strategy implemented in Texas included four elements: a mental health screening administered within 72 hours of the child being removed from the original caregiver; a health passport drawing on claims-based data; a psychiatric consultation line for child welfare staff, caregivers and judges; and a retrospective review of whether prescribed psychotropic medications met state best practice parameters after the antipsychotic medication was prescribed and dispensed.
The study, sought to examine whether the Texas program was effective in reducing the number of youth in foster care prescribed antipsychotic medications off-label to manage symptoms of conditions such as conduct disorders or attention hyperactivity disorders, while not decreasing use for disorders with FDA indications, such as bipolar disorder or autism spectrum disorders.
After the strategy started, the Rutgers researchers found the program resulted in roughly a 5 percent to 8 percent reduction in antipsychotic use for youth treated off-label for conditions like conduct or attention hyperactivity disorders, whereas no significant changes were found for youth treated for FDA-indicated conditions.
These findings show that the Texas program effectively reduced use of antipsychotic medications for off-label conditions where clinical concerns are greatest while not reducing antipsychotic medications for FDA-indicated conditions where stronger evidence exists for antipsychotic use among youth.
“Although the Texas model enrolled only youths in foster care, similar innovations are increasingly being extended to the general population of Medicaid-insured youth,” Mackie said. “This study provides important new evidence suggesting that states continue to incorporate or renew the inclusion of these additional behavioral health services into Medicaid-managed care arrangements.”
UC Davis research suggests a predictive role to support earlier intervention
Preschool-age girls with autism spectrum disorder (ASD) face greater challenges with emotional and behavioral problems than similar age boys with ASD. These challenges are associated with a larger amygdala, a UC Davis Health study has found. The amygdala is a key part of the brain that helps regulate emotions and detects threats.
The findings, by Christine Wu Nordahl, associate professor in the UC Davis Department of Psychiatry and Behavioral Sciences, and colleagues at the UC Davis MIND Institute, suggest that amygdala development may help predict these psychological and behavioral problems that can occur at high rates in girls with ASD. The study was published online Jan. 19 in the Journal of the American Academy of Child & Adolescent Psychiatry.
“A significant number of individuals with autism have co-occurring psychiatric problems like ADHD, anxiety and depression,” said Nordahl, a scientist who specializes in neuroimaging. “There are treatments for these conditions that can reduce the challenges in their lives. But less is known about whether these problems are present in very young kids.
“I was interested in looking for early signs of these symptoms in 3-year-olds with autism and whether girls and boys are affected at the same rates. I also wanted to investigate the underlying brain basis for these symptoms. The amygdala is a likely target because of its role in emotion regulation. Amygdala enlargement has been reported both in autism as well as psychiatric problems like anxiety.”
Psychopathology symptoms in very young children can include frequent crying, poor eating habits, trouble sleeping, overeating, little interest in daily activities, inability to sleep alone, nervousness, frequent panic, inability to sit still or concentrate and being highly demanding.
Study focused on 3-year-olds diagnosed with autism
This study included 420 children (91 girls and 209 boys with ASD, and 57 girls and 63 boys developing typically who served as the control group). The scientists conducted MRI scans on 346 children as they slept to evaluate amygdala volume. Study participants also were evaluated on their psychopathology symptoms, as reported by a parent, as well as their adaptive functioning, cognitive development (IQ) and autism severity.
Researchers identified three subgroups of children with ASD:
- Over one quarter of the 3-year-olds with ASD (27%) had very high symptoms of psychopathology with moderate impairments on other measures such as IQ, daily living skills, and autism severity
- 40% had low levels of psychopathology and low levels of impairment on the other measures
- 32% had low levels of psychopathology but high levels of impairment on the other measures
Notably, a surprisingly high proportion of girls with autism (40%) were in the subgroup with very high levels of psychopathology. The remaining 60% of girls with ASD were more evenly split across the two other groups. In contrast, only about 20% of boys with autism were in the subgroup with high levels of psychopathology, and most boys (45%) were in the subgroups with the lowest levels of impairment on all measures.
When examining associations between amygdala volume and the subgroups of children with ASD, they found amygdala enlargement only in the children who also had high levels of psychopathology. They also found that the size of the amygdala was correlated with the severity of the problems in girls, but not boys.
“We think the larger amygdala volume is playing a role in these other co-occurring problems,” Nordahl said. “And the amygdala is playing more of a role in these problem behaviors in girls than in boys.”
Study sheds light on biological differences in girls with autism
The research is significant because it begins to explain some of the biological differences in girls with ASD, who are diagnosed with autism much less frequently than boys at a ratio of about 1 girl for every 4 boys, Nordahl said.
“Girls are really underrepresented in autism research, particularly in neuroimaging studies,” she said. “Because there are so many more boys than girls diagnosed with autism, girls are harder to recruit, and most studies do not include enough girls to meaningfully evaluate potential sex differences. The result is that we know very little about how girls with autism may be similar or different from boys, particularly from a neurobiological perspective.”
The findings are among the first to come out of the Girls with Autism Imaging of Neurodevelopment (GAIN) study at the MIND Institute, which seeks to better understand their brain structure and connectivity patterns. With nearly 100 girls with autism enrolled, it is the largest neuroimaging study ever conducted in very young girls at the time of diagnosis.
“Over the past decade, our research team has spent countless nights at the UC Davis Imaging Research Center working with families to help children feel comfortable enough to fall asleep for an MRI scan. Across several projects, our team has collected over 1,000 MRI scans in more than 450 children.”
Researchers to continue to follow participants into adolescence
Researchers hope to follow the study participants into middle childhood and adolescence. Those are the years when psychiatric conditions such as anxiety and depression are typically diagnosed.
“We want to continue to see how the amygdala develops and determine whether it will have a predictive role in the outcomes for these kids,” said Nordahl.
Until then, she said, the current findings may be helpful for parents with young children diagnosed with autism.
“It’s important for parents to be on the lookout for problem behaviors co-occurring with autism, particularly in girls,” said Nordahl. “If we can detect symptoms of psychopathology earlier, we may be able to intervene earlier to help children and their families before psychiatric problems become too debilitating.”
Other authors on the study include Ana-Maria Iosif, Gregory S. Young, Alexa Hechtman, Brianna Heath, Joshua K. Lee, Breanna Winder-Patel, David G. Amaral, Sally Rogers, Marjorie Solomon and Sally Ozonoff, all of UC Davis Health, and Lauren Libero and Vanessa P. Reinhardt, former post-doctoral researchers at the MIND Institute.
The research was funded with grants from the National Institutes of Health (RO1MH104438, R01MH103284, R01MH103371) and UC Davis MIND Institute. The project also was supported by the MIND Institute Intellectual and Developmental Disabilities Research Center (U54HD079125), MIND Institute Autism Center of Excellence (P50 HD093079), the MIND Institute Autism Research Training Program (T32MH073124) and University of California President’s Postdoctoral Fellowship.
The human dopamine transporter protein is missing a single amino acid.
A mutant gene that encodes a brain protein in a child with autism has been placed into the brains of fruit flies. Fruit flies hosting that gene produce the variant human brain protein and show abnormal behaviors of fear, repetitive activity and altered social interaction, reminiscent of autism impairments.
The genetic variant was found in the Simon Simplex Collection, which has collected genetic samples from 2,600 simplex families with autism spectrum disorder, or ASD. The brain protein is the dopamine transporter, or DAT, whose job is to pump the neurotransmitter dopamine back into nerve cells once the neurotransmitter has been released. The mutant protein is missing a single amino acid.
A study of this variant DAT — from its impaired molecular mechanism to its effect on fruit fly behavior — has been published in Proceedings of the National Academy of Sciences by co-corresponding authors Aurelio Galli, Ph.D., and Eric Gouaux, Ph.D.
Galli is professor in the Department of Surgery at the University of Alabama at Birmingham, and Gouaux is professor in the Vollum Institute at the Oregon Health & Science University and Howard Hughes Medical Institute.
Researchers found that fruit flies with the human variant DAT, or vDAT, are hyperactive. They had increased locomotor activity in both day and night, as compared with normal fruit flies. They also showed repetitive behavior — the vDAT fruit flies groomed themselves 23 percent of the time, versus 6 percent of the time for normal fruit flies. Repetitive behavior like self-grooming has been observed in animal models of neuropsychiatric disorders.
The vDAT fruit flies were also more fearful than normal fruit flies. In response to the sound of a predatory wasp, normal flies froze for about 150 milliseconds, and then they fled, as shown by a distinctive and rapid increase in average velocity that was captured by a 1,000-frame per second camera. In contrast, the vDAT fruit flies froze at the sound of the predator and showed little signs of fleeing during 600 milliseconds.
The vDAT fruit flies had impaired social interaction, as measured by changes in grouping. Many animal populations form temporary or permanent groups, such as flocks, schools or herds, that aid survival in the face of predators. Fleeing, in response to a threat, is an escape behavior where the flock size may compress or expand. The researchers found that normal fruit flies expanded their flock size in response to a threat — the sound of the predator wasp. The vDAT fruit flies, in contrast, compressed their flock size.
Besides the fruit fly behavior, the PNAS study is a comprehensive multidisciplinary approach that gets at some root causes of autism to a degree of detail that could make potential therapeutic treatments more realizable in the future.
Besides vDAT, the labs of Galli and Heinrich Matthies, Ph.D., assistant professor in the UAB Department of Surgery, have identified several other mutations in the human DAT gene that affect DAT function in individuals with ASD. For these people, disruption of dopamine transport appears to be a risk factor that promotes complications associated with ASD.
“The experimental paradigms we describe here,” Galli said, “provide a framework for molecular and behavioral analysis of novel DAT variants that are discovered by genetic analyses of individuals with ASD or related neuropsychiatric illness, as well as other disease-linked mutants that are emerging from precision medicine initiatives.”
Galli and Gouaux’s PNAS research went from human genetics to a basic animal model with simplified behavior, as detected by a new high-powered analysis. It investigated the underlying molecular mechanisms and basic biological functions with ever greater resolution, through studies at the cell level and all the way down to a bacterial system. Each added system was more fundamental with regard to biological complexity and phylogenetic level.
Details of vDAT structure and function
Besides altered fly behavior caused by the mutant protein, the PNAS study probed the molecular structure and function of vDAT using mutation of a related transporter protein from a thermophilic bacterium as a model. Experiments included X-ray crystallography, spin resonance spectroscopy, molecular modeling, cell culture studies and electrophysiology studies of fruit fly brains expressing the mutant.
The researchers showed that vDAT cells have impaired dopamine transport and impaired DAT-mediated electrical currents. Also, expression of the human vDAT reduced dopamine uptake in the whole brain of fruit flies. These findings support the idea that human DAT dysfunction in ASD stems from specific and yet distinct mechanisms.
To probe the mechanism of impaired transporter function, researchers used the related bacterial transporter as a model. They removed the single amino acid from the related bacterial transporter that correlates with the single amino acid missing in vDAT. Like DAT, the bacterial transporter protein embeds across the cell membrane and has domains called the extracellular gate and the intracellular gate to receive and release the molecule being transported from outside the cell to inside.
Deletion of the single amino acid altered conformation of the bacterial protein and appeared to lock its extracellular gate, apparently through disrupted hydrogen bonds between amino acids of the protein that abnormally left the intracellular gate in a conformation called “half-open and inward facing.” Molecular dynamics simulation of vDAT showed similar conformational changes and altered hydrogen bonding.
Co-authors with Galli, Gouaux and Matthies for the paper, “Structural, functional, and behavioral insights of dopamine dysfunction revealed by a deletion in SLC6A3,” are Nicholas G. Campbell, Aparna Shekar, Dungeng Peng, Amanda M. Duran, Brian O’Grady, Ramnarayan Ramachandran, James S. Sutcliffe, Jens Meiler, Leon M. Bellan and Hassane S. Mchaourab, Vanderbilt University; Jenny I. Aguilar and Kevin Erreger, Department of Surgery, UAB School of Medicine; Vikas Navratna and Dongxue Yang, Vollum Institute, Oregon Health and Science University; Alexander N. Morley, Harald H. Sitte and Thomas Stockner, Medical University of Vienna, Austria; and Greta Galli, University School of Nashville, Tennessee.
Mchaourab is co-senior author with Galli, and Greta Galli is daughter of Aurelio Galli.
Support for this work came from National Institutes of Health grants MH070039, GM080403, HL122010, DA35263, DA38058 and NS007491-14.
Children’s of Alabama Expands Sensory Pathway For Patients With Sensory Sensitivities
When Sladen Fisher got a bad cut on his earlobe at school, his mother, Jennifer Fisher, worried the sights and sounds of Children’s of Alabama’s Emergency Department would be too stressful for her son. That’s because Sladen has attention deficit hyperactivity disorder (ADHD) and sensory processing disorder.
At the time of the Sladen’s visit, Children’s of Alabama had just launched its Sensory Pathway, designed for patients with conditions such as ADHD, autism and Down syndrome. In 2016, the pathway began as a pilot project in the Emergency Department; however, it has since expanded to One Day Surgery and several inpatient units at Children’s of Alabama, including the Pediatric Intensive Care Unit, Pulmonary Care Unit and Special Care Unit. Future plans include expansion to ancillary and outpatient services.
The pathway made a lasting impact on Sladen. Back at school a few weeks later, he presented a report about someone he considers a hero. He chose Children’s of Alabama Child Life Specialist Shelby Smith, who stayed by his side during his visit, explained his treatment in terms he understood and provided him with an iPad and fidget toys for distraction and comfort.
“In his mind, she was a hero, someone who went above and beyond to help him,” Jennifer said. She made what could have been an incredibly difficult situation so amazing. She really was our hero.”The pathway has been equally impactful on Children’s of Alabama, said Michele Kong, M.D. associate professor in pediatric critical care at the University of Alabama at Birmingham (UAB) Department of Pediatrics.
“The pathway has been so empowering for our providers,” said Kong, who serves on the Sensory Pathway Task Force, also comprised of nurses, informatics specialists and child life specialists. Unit by unit, the task force provides education and training and is developing an online training module. The task force is also working with information technology specialists to flag patients with sensory sensitivities from the point of admission.
“We tailor education and training to suit each unit’s needs because each unit’s workflow and culture is different,” Kong said. “The success of the pathway is a direct reflection of our providers’ passion to learn. There’s buy-in from our providers because they know it’s good for their patients.”
As a parent, Kong, too, knows how jarring a hospital visit can be for a child with sensory sensitivities. Her oldest son, Abram, was diagnosed with autism at age 4. The diagnosis inspired Kong and her husband, Julian Maha, M.D., to found KultureCity®, a nonprofit that works to “create acceptance and inclusion for all individuals with unique abilities,” according to its mission statement. In 2019, KultureCity was ranked fourth on Fast Company magazine’s list of the most innovative companies in the world. KultureCity not only partners with local organizations in Birmingham, but also with national organizations such as the NBA and NFL.
“We never imagined it would reach this scale,” Kong said. “It impressed on us that there’s a lot of power when a collective group of people have the same belief and passion for change.”
Breakthrough research demonstrating that children with autism as young as 18 months can vastly improve their language, cognition and social skills with an early intervention developed by UC Davis Professor Sally Rogers has been replicated in a major new study.
Rogers, a professor of Psychiatry and Behavioral Sciences at the MIND Institute, began work on a novel developmental approach to autism in Denver in 1981, and in partnership with her colleague and co-author Geraldine Dawson developed an approach to improving long-term outcomes for very young children. The Early Start Denver Model has since become a method used throughout the U.S. and around the world.
But until now ESDM had not been tested in the most rigorous fashion − a multi-site randomized trial, comparing the approach with community-based autism interventions. The study, which appears today in Journal of the American Academy of Child and Adolescent Psychiatry, began in 2007 at three university sites around the country. The new research replicates an ESDM study published in 2010. Rogers emphasized that replication studies are rare and costly but critical to validate novel scientific findings.
The new study found that children receiving intensive ESDM in their homes for an average of 15 hours per week made significantly greater language gains than did children in the community interventions, and this was true for both children with more severe delays and those with less.
In addition to validating the efficacy of ESDM for language development, the study also found that children receiving services in the community settings made large gains in several areas.
“The idea that little children with autism who are getting good treatment can make this much IQ and language gain means we should expect this from quality early-intervention experiences,” Rogers said. “These findings should raise families’ hopes a whole lot.”
Pioneering autism treatment was a new idea
What distinguishes ESDM from the more traditional, behavioral interventions used with children with autism is that it combines developmental and behavioral approaches and is carried out within in everyday routines. ESDM is built on moment-to-moment interactions that young children typically have with other people, especially their parents, and uses children’s interests and favorite activities to assure that social interaction is interesting and fun.
“Unlike other approaches popular at the time that the Denver Model began, we used a typical preschool physical environment and focused on the learning opportunities that existed in social interactions between children and adults to accelerate children’s development,” Rogers said. “This was a new idea at the time.”
In 2012, TIME magazine named ESDM one of the top 10 medical breakthroughs because their work demonstrated that brain function among young children with autism can normalize with effective early intervention in profound, enduring ways.
For the current study 118 children with autism, ages 14 months to two years, were enrolled and randomly assigned to either ESDM or community interventions for 27 months. Children assigned to ESDM intervention received three months of weekly parent coaching followed by 24 months of one-on-one treatment about 15 hours per week in homes or daycare settings from supervised therapy assistants. Parents received coaching four hours monthly from a certified ESDM therapist. In the community setting, hours of treatment varied by site.
What researchers found was that at two of the three sites, children receiving ESDM had significantly more language improvement than the children in the community interventions, and there was no significant difference in language gain at the third site between the two modalities. When results from all three sites were pooled, there was a significant advantage for the children in the ESDM group overall.
“Language is the bridge to learning,” Rogers said. “Language is the door that opens up social communication and education and interactions with people in your community. It’s how you share with people. It’s a main vehicle for social interaction once you pass infancy.”
Autism treatment in the community greatly improved over time
The study also found that in terms of cognition and social skills, both the ESDM and community treatment groups made significant gains. Fortunately, Rogers said, laws requiring insurance coverage for early autism intervention and new knowledge about effective treatment have greatly improved community options for families seeking help for young children diagnosed with autism.
Rogers said families with a child diagnosed with autism should take some comfort knowing that the early treatments now widely available do make a difference.
“It says the autism scores at the time of diagnosis are just a starting point,” she said. “It says that the developmental paths and learning capacity of young children with autism are more plastic than we knew, and there are many ways to get learning opportunities to them.”
In addition to Rogers, UC Davis authors on the study were Marie Rocha, Laurie Vismara and Meagan Talbott. Other co-authors on the study included: Annette Estes and Jessica Greenson of the University of Washington; Catherine Lord and Jamie Winter of Weill Cornell Medicine, Cornell University; Costanza Colombi of University of Michigan; Geraldine Dawson of Duke University, and Gerhard Hellemann of UCLA.
This study was supported by individual Autism Speaks grants to Annette Estes and to Sally Rogers and by NIMH/NICHD award number R01 081757 as part of the Autism Centers of Excellence (ACE) Treatment Network, clinicaltrials.gov identifier NCT 00698997.
In recent days there has been significant coverage surrounding the Boca Raton native becoming the first openly autistic person to be admitted to the Florida bar. This accomplishment being widely accepted is a huge stride for those diagnosed with autism and autism professionals working hard to create inclusive workplaces.
To help others understand why inclusivity and supporting those with disorders is so important, I’d like to offer Arianna Esposito, Associate Director of Adult & Transition Programs at the Kinney Center for Autism Education and Support at Saint Joseph’s University. She is able to offer tips to help employers create an inclusive workplace. These tips are not only helpful for individuals with autism, but can benefit all employees. Please see a sampling of her advice below:
- Sensory-Friendly Environment
Fluorescent lights can be extremely bothersome for someone with sensory challenges. Offering dimmer lighting options or access to natural light are good alternatives. Odorless office supplies, cleaning supplies and other products are recommended to have in a supply closet or open areas. Designated, private quiet rooms for employees to take a call in or do work are a great option.
- Open communication
Providing clear and specific feedback is important for an inclusive structure. Try putting a positive spin on code of conduct by turning “do not” rules into “can do” rules.
Being flexible with needs such as accepting requests to wear specific clothing items and seating locations (not near crowded areas) will help individuals navigate the social world.
Ten Signs of Possible Autism-Related Delays in 6- to 12-Month-Old Children
Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.
According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays. “We want to encourage parents to become good observers of their children’s development so that they can see the earliest indicators of delays in a baby’s communication, social and motor skills,” says Dr. Landa, who also cautions that some children who develop ASD don’t show signs until after the second birthday or regress after appearing to develop typically.
For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old. Dr. Landa recommends that as parents play with their infant (6 – 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders: 1. Rarely smiles when approached by caregivers2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges3. Delayed or infrequent babbling4. Does not respond to his or her name with increasing consistency from 6 – 12 months 5. Does not gesture to communicate by 10 months6. Poor eye contact7. Seeks your attention infrequently8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors9. Does not reach up toward you when you reach to pick him or her up10. Delays in motor development, including delayed rolling over, pushing up and crawling
“If parents suspect something is wrong with their child’s development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert,” says Dr. Landa. “Don’t adopt a ‘wait and see’ perspective. We want to identify delays early in development so that intervention can begin when children’s brains are more malleable and still developing their circuitry.”
About the Kennedy Krieger Institute Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 16,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit: www.kennedykrieger.org.
UCLA-led team compares DNA of children with the disorder to that of their siblings and parents
A UCLA-led research team has identified dozens of genes, including 16 new genes, that increase the risk of autism spectrum disorder. The findings, published in the journal Cell, were based on a study of families with at least two children with autism.
Researchers from UCLA, Stanford University and three other institutions used a technique called whole genome sequencing to map the DNA of 2,300 people from nearly 500 families. They found 69 genes that increase the risk for autism spectrum disorder; 16 of those genes were not previously suspected to be associated with a risk for autism.
Researchers also identified several hundred genes they suspect may increase the risk of autism based on their proximity to genes previously identified to carry an increased risk. The study analyses further revealed several new biological pathways not previously identified in studies of autism.
The findings shed light on how genetic variants or mutations — the differences that make each person’s genome unique — are passed from parents to children affected with autism, said the study’s co-lead author Elizabeth Ruzzo, a UCLA postdoctoral scholar. Former UCLA postdoctoral scholar Laura Pérez-Cano is the study’s other co-lead author.
“When we look at parents of autistic children and compare them to individuals without autism, we find that those parents carry significantly more, rare and highly damaging gene variants,” Ruzzo said. “Interestingly, these variants are frequently passed from the parents to all of the affected children but none of the unaffected children, which tells us that they are significantly increasing the risk of autism.”
Of the children in the study, 960 have autism and 217 children do not. That enabled researchers to analyze the genetic differences between children with and without autism across different families.
“Studying families with multiple children affected with autism increased our ability to detect inherited mutations in autism spectrum disorder,” said Dr. Daniel Geschwind, senior, corresponding author of the study and the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at the David Geffen School of Medicine of UCLA.
“We show a substantial difference between the types of mutations that occur in different types of families, such as those that have more than one affected child versus those having only one child with ASD,” said Geschwind, who also was the study’s co-principal investigator and director of the UCLA Center for Autism Research and Treatment and director of the Institute of Precision Health at UCLA.
The research also found that the 16 genes newly determined to be associated with an increased risk for autism form a network with previously identified ASD risk genes. The way they interact with one another further heightens the risk, said the study’s co-senior author and co-principal investigator Dennis Wall, a Stanford University School of Medicine associate professor of pediatrics and of biomedical data science.
“They associate with each other more tightly than we’d expect by chance,” he said. “These genes are talking to each other, and those interactions appear to be an important link to autism spectrum disorder.”
The nearly 600 genes researchers suspect as carrying an increased risk of autism were identified through “guilt by association,” or through their interactions with other genes that already have been shown to carry an increased autism risk, Ruzzo said.
“And although not all of those genes will be found to increase the risk for autism, our analysis indicates that future studies will provide support for many of these genes,” she said.
The families studied are part of the Autism Genetic Resource Exchange (AGRE), which was originally developed nearly two decades ago by researchers and the National Institutes of Health in collaboration with Cure Autism Now, which is now a program of Autism Speaks.
Autism is a spectrum of neurological disorders characterized by difficulties with communication and social interaction. Geschwind has been working to identify the genetic causes and biological mechanisms of the disorder for more than a decade, and led the original development of the AGRE resource that was used in this study in the late 1990s. In 2018, he and colleagues at UCLA received their second, five-year grant from the NIH to expand autism research by studying genetic causes of autism in African American families.