NSF grant supports research to develop new models to better understand the brain
TROY, N.Y. — When Sergio Pequito thinks about the brain, he visualizes a piano. The keys represent different parts of the brain, and the pressure applied by the pianist’s fingers represents the outside stimuli that promote brain functions.
Just as notes and harmonies can be mapped onto sheet music, Pequito, an assistant professor of industrial and systems engineering at Rensselaer Polytechnic Institute, is looking to transcribe the brain’s complex dynamics into new data models that can help researchers better understand how the brain and human cognition work. This composition effort, of sorts, is being supported by a new grant from the National Science Foundation.
“We have showed that, by thinking like this, there was a lot of activity in the brain that we were able to mimic and capture,” Pequito said. “We believe that we can use the math and models we have developed to capture intrinsic features that justify how the brain behaves over space and time.”
Pequito’s team, which includes a collaborator from the University of Southern California, will use publicly available brain signal data from the National Institutes of Health to improve the models they have built. The data has been collected using functional magnetic resonance imaging (fMRI) technology, which tracks blood and oxygen flow as they increase in active parts of the brain.
Pequito and his team are trying to provide insight into how a healthy brain functions, as well as how one with a neurological disease may behave. Continuing this analogy, Pequito explained that just as a pianist who hits the wrong key may create a dissonant noise, the models developed by his research team will show when something is a bit off in the brain’s activity.
Industrial and systems engineers develop tools to analyze how complex systems interact. Pequito believes that this type of approach to humanity’s long-standing questions about the brain can provide new understanding about the relationships between functions like attention, learning, memory, decision-making, and language. These insights may prove useful in improving current technology by reverse-engineering the brain, which is one of the National Academy of Engineering’s Grand Challenges for Engineering.
“We have all sorts of tools that we, as industrial engineers, can use,” Pequito said. “Now, we are working to improve them so we can provide new insights for the neuroscience and medical community.”
It is not uncommon for children and teens with autism spectrum disorder to struggle with sleep. Trouble falling asleep and staying asleep or refusing to go to bed are just some of the sleep problems they can experience. To help families, neurologists and other healthcare providers make decisions on the best treatments, the American Academy of Neurology (AAN) has issued a new guideline for sleep problems in children and teens with autism, published in the February 12, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The guideline is endorsed by the American Academy of Sleep Medicine, Autism Speaks, the Child Neurology Society and the Society for Developmental and Behavioral Pediatrics. The American Epilepsy Society has affirmed the value of the guideline to epileptologists.
“While up to 40 percent of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” said lead guideline author Ashura Williams Buckley, MD, of the National Institute of Mental Health in Bethesda, Md., and a member of the American Academy of Neurology. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
For the guideline, experts from the American Academy of Neurology carefully reviewed available scientific studies on autism and sleep problems in children and teens.
The guideline addressed four types of sleep problems: refusing to go to bed, stalling, or needing a parent or caregiver present until the child falls asleep; trouble falling asleep and staying asleep; sleeping for only short periods of time or not getting enough total sleep each night; and daytime behavior problems associated with insufficient sleep at night.
The guideline recommends that healthcare providers first identify if the sleep problems are caused by medications or other medical conditions, and if so, that those causes be addressed.
If sleep problems appear to be more behavioral in nature, the guideline recommends a number of behavior treatments that have been shown to be effective in children with autism. These include setting up a consistent sleep routine with regular bedtimes and wake times, choosing a bedtime close to when the child usually gets sleepy, and not allowing use of electronic devices like computers or televisions close to bedtime.
“Behavior-modification strategies are a good place to start because they do not cost anything, there are no side effects and they have been shown to work for some people,” said Williams Buckley.
If behavioral strategies alone do not work, the guideline recommends that healthcare providers also consider adding melatonin.
Melatonin is a hormone that tells the brain when to fall asleep and how long to sleep. Studies suggest that the artificial form of melatonin is safe and effective for children and teens with autism in the short term, for a period of up to three months. More research is needed to determine how safe melatonin is over longer periods of time. Possible side effects include headache, dizziness, diarrhea and rash. The guideline also cautions that over the counter melatonin products may not be reliable in terms of how much melatonin they actually contain. The guideline recommends using products that are labeled “pharmaceutical grade” melatonin.
The guideline also found that melatonin use alone may be just as helpful in some patients as when melatonin is combined with behavioral strategies.
The guideline did not find that behavior treatments combined with melatonin changed daytime behavior problems or symptoms of autism.
The guideline also found no evidence that routine use of weighted blankets or specialized mattress technologies improve sleep.
“Sleep problems can make behavioral issues in children and teens with autism even worse,” said Williams Buckley. “That’s why it is important for parents and caregivers to work with healthcare providers to find a way to improve a child’s sleep because we know that good quality sleep can improve overall health and quality of life in all children.”
Learn more about autism at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.
The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.
Researchers Use SDSC’s ‘Comet’ Supercomputer to Analyze Genome Sequences
While the causes of autism spectrum disorder (ASD) are not fully understood, researchers believe both genetics and environment play a role. In some cases, the disorder is linked to de novo mutations that appear only in the child and are not inherited from either parent’s DNA.
In a recent study published in Nature Medicine, an international team of scientists led by researchers at University of California San Diego School of Medicine describe a method to measure disease-causing mutations found only in the sperm of the father, providing a more accurate assessment of ASD risk in future children.
“Autism afflicts one in 59 children and we know that a significant portion is caused by these de novo DNA mutations, yet we are still blind to when and where these mutations will occur,” said co-senior author Jonathan Sebat, professor and chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine. “With our new study, we can trace some of these mutations back to the father, and we can directly assess the risk of these same mutations occurring again in future children.”
The research team used the Comet supercomputer based at the San Diego Supercomputer Center, an Organized Research Unit of UC San Diego, to align the whole genome sequences. “We called variants on the sequences and also detected de novo variants using Comet for these samples,” explained Danny Antaki, a UC San Diego Neurosciences postdoctoral scholar. “In short, Comet provided the foundation for the larger experiment as we were able to find the de novos that we wanted to analyze in sperm with the data generated on the supercomputer.”
Recent studies suggest gene-damaging de novo mutations are involved in at least 10 to 30 percent of ASD cases, with the number of mutations rising with the father’s age at time of conception. De novo mutations occur spontaneously in parents’ sperm or eggs or during fertilization. The mutation is then present in each cell as the fertilized egg divides.
Studies now point to male sperm as a particularly important source of these mutations, with the chance of the mutation recurring within the same family generally estimated at 1 to 3 percent.
“However, such estimates are not based on actual knowledge of the risk in an individual family, but instead are based on frequencies in the general population,” said co-senior study author Joseph Gleeson, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine. “When a disease-causing mutation occurs for the first time in a family, the probability that it could happen again in future offspring is not known. Thus, families must make a decision with a great deal of uncertainty.”
For their study, Gleeson, Sebat, and colleagues analyzed the sperm of eight fathers who were already parents of children with ASD. The goal was to look for the presence of multiple, genetically different material in cells in the same person, a phenomenon called mosaicism. Using deep whole genome sequencing, they found variants in offspring that were matched only in the fathers’ sperm.
“While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct,” said first author Martin Breuss, an assistant project scientist in Gleeson’s lab. “Mutations occur every time a cell divides, so no two cells in the body are genetically identical. Mosaicism can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body. But if a mutation happens just in sperm, then it can show up in a future child but not cause any disease in the father.”
The researchers determined that disease-causing mutations were present in up to 15 percent of the fathers’ sperm cells, information that could not be determined through other means, such as blood samples.
“My laboratory has a long-standing interest in understanding the origins of pediatric brain disease, and how mutations contribute to disease in a child,” said Gleeson. “We previously showed that mosaicism in a child can lead to diseases like epilepsy. Here, we show that mosaicism in one of parents is at least as important when thinking about genetic counseling.”
If developed into a clinical test, the researchers said fathers could have their sperm studied to determine their precise risk of recurrence in future children. The methods might also be applied to men that haven’t had children yet, but who want to know the risk of having a child with a disease.
About UC San Diego Health
UC San Diego Health, comprising a comprehensive health system throughout San Diego County, UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, is one of five academic medical systems within the University of California system. We are committed to improving patient care while also researching new treatments and training tomorrow’s doctors and pharmacists. For more than 50 years, our renowned clinicians and scientists have made advances in numerous fields, including minimally invasive surgeries, personalized cancer therapy, cardiovascular treatment and surgery, transplantation and the early detection of autism.
As an Organized Unit of UC San Diego, SDSC is considered a leader in data-intensive computing and cyberinfrastructure, providing resources, services, and expertise to the national research community, including industry and academia. SDSC supports hundreds of multidisciplinary programs spanning a wide variety of domains, from earth sciences and biology to astrophysics, bioinformatics, and health IT. SDSC’s petascale Comet supercomputer is a key resource within the National Science Foundation’s XSEDE (eXtreme Science and Engineering Discovery Environment) program.
New research study will analyze dried blood spots recorded from California newborns for 1,000 different molecules and chemicals; their tell-tale presence might predict autism risk years before symptoms appear, prompting early treatment and perhaps prevention
Within days of birth, a few drops of blood are collected from every newborn in California—and across the United States — which are then stored on filter paper and screened for dozens of genetic and congenital disorders, such as phenylketonuria (PKU), an inherited metabolic disorder that can result in intellectual disability, seizures, heart and behavioral problems.
Researchers at University of California San Diego School of Medicine have launched a Phase II research study to look for signs of another similarly devastating disorder, one that typically does not appear in seemingly healthy children until years later: autism spectrum disorder or ASD.
The UC San Diego Newborn Screening-Autism Risk Study is designed to determine whether the dried and stored blood drops of children later diagnosed with ASD contain within them the tell-tale presence and combinations of biological molecules and environmental chemicals that might predict the risk of a future ASD diagnosis.
“We know from the history of certain genetic diseases, such as PKU, that if children can be identified before the first symptoms have appeared, then the disease can be prevented, even though the children have the DNA mutations,” said Principal Investigator Robert Naviaux, MD, PhD, professor of medicine, pediatrics and pathology at UC San Diego School of Medicine. “I believe that over half of autism cases may be preventable if only we had a way to identify the children at risk before the first symptoms appear.”
Naviaux said the new study is important for two reasons: the dramatic rise in diagnosed cases of ASD and increasing evidence that early intervention in children at risk of ASD can significantly improve outcomes.
The prevalence of ASD has risen from 20 in 100,000 births in the 1970s to 1,700 in 100,000 in 2014, according to the U.S. Centers for Disease Control and Prevention — an 84-times increase. Approximately one in 59 children is diagnosed with ASD. Statistics from the U.S. Department of Education and other government agencies indicate autism diagnoses are increasing at the rate of 10 to 17 percent per year.
Changes in diagnostic criteria and reporting practices account for 60 percent of the rise, at most, according to previously published research. “This means that even by the most conservative estimates, the prevalence of ASD has increased at least 34 times,” said Naviaux. The overarching question for Naviaux and others is why? Is it genetics? The environment?
“Our genes have not changed significantly in the past 50 years,” said Naviaux. Single gene mutations play a causal role in approximately 10 percent of ASD cases. The vast majority of ASD cases are idiopathic or of unknown cause, most likely the result of a combination of genes, environmental factors or something yet to be identified.
“More than 1,000 genes can contribute to the risk and resistance a child has to ASD, but more than 95 percent of these genes are common variations also present in asymptomatic parents and children who don’t have ASD,” Naviaux said. “A clue to how the genetics of ASD is misinterpreted is the fact that many of the genes that contribute to ASD are the same genes that contribute to other disorders like schizophrenia and bipolar depression. In most cases, DNA only sets what is possible, not what is destined.”
The new Phase II study will focus on exposure and possible roles of chemicals and compounds (detected in blood) and how they might interact with genes.
Researchers will use a blood test developed in Naviaux’s lab to analyze the presence of more than 600 metabolites —typically small molecules produced by metabolism, the life-sustaining chemical reactions in all organisms. Metabolites from amino acids and antioxidants to vitamins and lipids serve diverse, crucial functions, including as fuel, signal carriers, structure providers, defenders and regulators among them.
Earlier research by Naviaux and others has found that persons with ASD appear to have a shared “metabolic signature.” That is, their biological chemistry is comparable, though their genetics are unique.
Testing will also look at more than 400 environmental chemicals in each dried blood drop. Exposure to these chemicals, such as commonly used pesticides, flame retardants, air pollutants, lead, mercury and polychlorinated biphenyls or PCBs, has been linked to several neurodevelopmental disorders, including ASD.
Naviaux and colleagues believe that the majority of ASD symptoms are the result of a treatable metabolic syndrome triggered by persistence activation of the cell danger response (CDR), a natural and universal cellular reaction to injury or stress.
Chronic CDR, they suggest, results in disrupted and incomplete healing at the metabolic and cellular levels. In ASD, the consequence may be dysfunctional neural circuits and internal systems, producing autism’s well-documented symptoms and behaviors.
“Metabolism is the real-time result of our genes interacting with the environment,” said Naviaux. “Environmental chemical or biotoxin exposures —the ‘exposome’ — at critical developmental windows can produce delayed effects that become apparent only after months or years. By measuring metabolism and the exposome, it may be possible to identify children at risk for developing autism before the first behavioral symptoms appear.”
The study seeks 400 participants between the ages of three and 10 years old, meeting these requirements:
Born in California Have a confirmed diagnosis of ASD from a licensed clinician or be a healthy child not taking any prescription medications (200 participants from each group) Born after a normal term pregnancy of 37 to 42 weeks Have not had a medical issue that required readmission to the hospital in the first month of life
The study requires parents of participating children to answer questionnaires covering pregnancy, labor and delivery, the child’s health history and that of the family.
Consented analyses will be conducted of dried blood drops recorded as part of California’s Newborn Screening program, which began in 1966 and now screens for 80 different genetic and congenital disorders. Blood spots have been saved and stored by the California Department of Public Health since 1982. No new blood tests or behavioral testing will be required for the Phase II study.
Naviaux said he hopes to screen and enroll the full complement of participants by June 2020. Analyses of the identified and retrieved blood spots is expected to be complete by June 2021.
“We then hope to expand the testing program to states like New Jersey, New York, Pennsylvania and Washington by enlisting collaborators in each of those states who will be able to apply the new methods we have developed.
“Each new state has slightly different policies and regulations regarding the collection and storage of dried blood spots from universal newborn screening programs, so this medium-scale expansion study will teach us what will be needed to launch a national study.”
The standardized test, known as the Autism Diagnostic Observation Schedule (ADOS), assesses communication skills, social interaction and play for children who may have autism or other developmental disorders.
The researchers digitized the test by attaching wearable technology, like an Apple Watch, to two clinicians and 52 children who came in four times and took two different versions of the test.
When researchers looked at the scores of the entire cohort, they found they did not distribute normally – which could mean a chance of false positives inflating the prevalence of autism, among other implications.
“The ADOS test informs and steers much of the science of autism, and it has done great work thus far,” said Torres, whose expertise has brought emerging computer science technology to autism. “However, social interactions are much too complex and fast to be captured by the naked eye, particularly when the grader is biased to look for specific signs and to expect specific behaviors.”
The researchers suggest combining clinical observations with data from wearable biosensors, such as smartwatches, smartphones and other off-the-shelf technology.
By doing so, they argue, researchers may make data collection less invasive, lower the rate of false positives by using empirically derived statistics rather than assumed models, shorten the time to diagnosis, and make diagnoses more reliable, and more objective for all clinicians.
Torres said autism researchers should aim for tests that capture the accelerated rate of change of neurodevelopment to help develop treatments that slow down the aging of the nervous system.
“Autism affects one out of 34 children in New Jersey,” she said. “Reliance on observational tests that do not tackle the neurological conditions of the child from an early age could be dangerous. Clinical tests score a child based on expected aspects of behaviors. These data are useful, but subtle, spontaneous aspects of natural behaviors, which are more variable and less predictable, remain hidden. These hidden aspects of behavior may hold important keys for personalized treatments, like protecting nerve cells against damage, or impairment, which could delay or altogether stop progression.”
The study was co-authored by Richa Rai, a graduate student in psychology at Rutgers University, Sejal Mistry, a former Rutgers Biomathematics student now at the University of Utah Medical School, and Brenda Gupta from Montclair State University.
Neurobehavioral researchers at Rush University center have found three key factors during a child’s behavior which will cause social rejection. The studies are an important step in developing scientifically sound screening tests and treatment planning for social-emotional learning difficulties. The results from the studies are published within the Journal of Clinical Child and Adolescent Psychology.
Findings from the pair of studies indicate that the power to select abreast of non-verbal cues and social cues in social interaction also as recognize the meaning and respond appropriately to them are key to helping children develop skills to take care of friendships and avoid a number of problems in later life.
A child who experiences social rejection is more likely to suffer from academic failure, drop out of faculty, experience depression or anxiety, and experiment with drugs.
“Children’s ability to develop positive peer relationships is critical to their well-being,” said Dr. Clark McKown, study PI and associate executive and director of research at the push Neurobehavioral Center. “Compared to children who are accepted by their peers, socially rejected children are at substantially elevated risk for later adjustment troubles.”
Researchers observed two groups of youngsters. One was a random sample of 158 children within the Chicago establishment. the opposite group was a random sample of 126 clinic-referred children.
The studies indicate that some children have difficulty learning on non-verbal or social cues.
According to McKown, “They simply don’t notice the way someone’s shoulders slump with disappointment, or hear the change in someone’s voice once they are excited, or absorb whether a person’s face shows anger or sadness.”
A second major factor is that some children may devour on non-verbal or social cues, but lack the power to connect aiming to them. The third factor is that the ability to reason about social problems.
“Some children may notice social cues and understand what’s happening, but are unable to try to to the social problem solving to behave appropriately,” said McKown.
A child who can absorb social cues, recognize their meaning and respond appropriately, and who is capable of “self- regulating,” or controlling behavior, is more likely to possess successful relationships.
“The number of youngsters who cannot negotiate of these steps, and who are in danger of social rejection, is startling,” said McKown.
Nearly 13 percent of the varsity age population, or roughly four million children nationwide, have social-emotional learning difficulties.
For some time, behavioral scientists have known the social costs related to this problem. Illinois is one among a couple of states which require school districts to assess and monitor the social-emotional learning needs of its students.
“Because it’s not known exactly which behaviors set a toddler up for failure, or the way to measure these skills, it had been difficult to supply support,” said McKown. “Now, it’ll be possible to pinpoint which abilities a toddler must develop and offer help.”
According to researchers at Rush, the results of the studies could potentially help develop tests to assess for social-emotional learning that are easy to administer and scientifically sound.
The study was funded by the Dean and Rosemarie Buntrock Foundation and therefore the William T. Grant Foundation.
About Rush University center Rush University Medical Center is a tutorial center that encompasses the quite 600 staffed-bed hospital (including Rush Children’s Hospital), the Johnston R. Bowman clinic and Rush University. Rush University, with quite 1,730 students, is home to at least one of the primary medical schools within the Midwest, and one among the nation’s top-ranked nursing colleges. Rush University also offers graduate programs in allied health and therefore the basic sciences. Rush is noted for bringing together clinical care and research to deal with major health problems, including arthritis and orthopedic disorders, cancer, heart condition, mental disease, neurological disorders and diseases related to aging.
About Rush Neuro Behavioral Center Rush Neuro Behavioral Center (RNBC) serves the medical, psychological and academic needs of youngsters with neuro behavioral issues with a special emphasis on social-emotional learning disorders. .These children have difficulty focusing, forming relationships, regulating behavior, or functioning effectively due to differences within the way their brains receive, process, and manage verbal and nonverbal information. Through research, clinical practice, and education, RNBC seeks to reinforce the understanding of the requirements of these with neuro behavioral disorders, repose on their strengths, and help them achieve their full potential.
Since 1997, RNBC has treated quite 10,000 children with such problems as Tourette’s Syndrome, Asperger’s Syndrome, autism spectrum disorders, attention deficit hyperactivity disorder, and language-based and non-verbal learning disabilities
Visit http://www.RNBC.org or call 847.933.9339 with any questions or additional information on RNBC services and research initiatives.
Technion student develops system that interprets sarcasm on Twitter, and translates it into sarcasm-free language
Researchers in the Technion-Israel Institute of Technology Faculty of Industrial Engineering and Management have developed a system for interpreting sarcastic statements in social media. The system, developed by graduate student Lotam Peled, under the guidance of Assistant Professor Roi Reichart, is called Sarcasm SIGN (sarcasm Sentimental Interpretation GeNerator).
“There are a lot of systems designed to identify sarcasm, but this is the first that is able to interpret sarcasm in written text,” said Peled. “We hope in the future, it will help people with autism and Asperger’s, who have difficulty interpreting sarcasm, irony and humor.”
Based on machine translation, the new system turns sarcastic sentences into honest (non-sarcastic) ones. It will, for example, turn a sarcastic sentence such as, “The new ‘Fast and Furious’ movie is awesome. #sarcasm” into the honest sentence, “The new Fast and Furious movie is terrible.”
Despite the vast development in this field, and the successes of sentiment analysis applications on “social media intelligence,” existing applications do not know how to interpret sarcasm, where the writer writes the opposite of what (s)he actually means.
In order to teach the system to produce accurate interpretations, the researchers compiled a database of 3,000 sarcastic tweets that were tagged with #sarcasm, where each tweet was interpreted into a non-sarcastic expression by five human experts. In addition, the system was trained to identify words with strong sarcastic sentiments – for example, the word “best” in the tweet, “best day ever” – and to replace them with strong words that reveal the true meaning of the text. The system was examined by a number of (human) judges, who gave its interpretations high scores of fluency and adequacy, agreeing that in most cases it produced a semantically and linguistically correct sentence.
Automatic identification and analysis of sentiment in text is a very complex challenge being explored by many researchers around the world because of its commercial potential and scientific importance. Sentiment identification could be used in social, commercial, and other applications to improve communication between people and computers, and between social media users.
The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.
American Technion Society (ATS) donors provide critical support for the Technion—more than $2 billion since its inception in 1940. Based in New York City, the ATS and its network of supporters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.
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.
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.”