Tag: Autism

Mutations in Sperm May Reveal Risk for Autism

Credit: Martin Breuss, UC San Diego Health
In this illustration of sperm mosaicism, mutated sperm are depicted in red.

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.

About SDSC

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.

Predicting Autism Risk

Credit: U.S. Government
At birth, blood samples are taken from newborns and used to screen for genetic diseases. A new research study will help determine whether these drops can also help predict autism risk.

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.”

Synchronization of Memory Cells Critical For Learning and Forming Memories

Credit: UNH

On the left is an enlarged image showing many hippocampal neurons, most of which are silent and only a few are active. On the right are close ups of three highly active neurons, or memory cells, which become synchronized after memory formation

The phrase “Pavlov’s dogs” has long evoked images of bells, food and salivating dogs. Even though this tried-and-true model of repetitive patterns mimics a variety of learning processes, what happens on a cellular level in the brain isn’t clear. Researchers at the University of New Hampshire took a closer look at the hippocampus, the part of the brain critical for long-term memory formation, and found that the neurons involved in so-called Pavlovian learning shift their behavior during the process and become more synchronized when a memory is being formed – a finding that helps better understand memory mechanisms and provides clues for the development of future therapies for memory-related diseases like dementia, autism and post-traumatic stress disorder (PTSD).

“There are tens of millions of neurons in the hippocampus but only a small fraction of them are involved in this learning process” said Xuanmao (Mao) Chen, assistant professor of neurobiology. “Before engaging in Pavlovian conditioning, these neurons are highly active, almost chaotic, without much coordination with each other, but during memory formation they change their pattern from random to synchronized, likely forging new connecting circuits in the brain to bridge two unrelated events.

In the study, recently published in The FASEB Journal, researchers looked at Pavlovian learning patterns, or respondent conditioning, in mice. In the beginning, before any repetitive learning exercises, the mice did not know what to expect and using special imaging with an endomicroscope the researchers saw that the neural activity was disorderly. But after repeating different tasks associated with a conditional stimulus, like a tone or bell, the mice began to recognize the pattern and the highly active neurons became more synchronized. The researchers hypothesize that without forming synchronization, animals cannot form or retrieve this type of memory.

In the 1890’s, Russian psychologist, Ivan Pavlov discovered classical conditioning through repetitive patterns of bell ringing which signaled to his dogs that food was on its way and stimulated salivation. This same learned behavior is important for episodic knowledge which is the basis for such things as learning vocabulary, textbook knowledge, and memorizing account passwords. Abnormal learning processing and memory formation are associated with a number of diseases like dementia, autism, and PTSD. People who struggle with these cognitive dysfunction-related disorders may have trouble retaining memories or can even form too strong a memory, as with PTSD patients. The UNH researchers believe that understanding the fundamentals of how classical conditioning shape neural connections in the brain could speed up the development of treatments for these disorders in the future.

Contributing to these findings are Yuxin Zhou, doctoral candidate; Liyan Qiu, research scientist; both at UNH, and Haiying Wang, assistant professor at the University of Connecticut.

This work was supported by the National Institutes of Health (NIH) and the Cole Neuroscience and Behavioral Faculty Research Awards.

The University of New Hampshire inspires innovation and transforms lives in our state, nation and world. More than 16,000 students from all 50 states and 71 countries engage with an award-winning faculty in top-ranked programs in business, engineering, law, health and human services, liberal arts and the sciences across more than 200 programs of study. As one of the nation’s highest-performing research universities, UNH partners with NASA, NOAA, NSF and NIH, and receives more than $110 million in competitive external funding every year to further explore and define the frontiers of land, sea and space. 

Schizophrenia Is A Disease, Not An Extreme of Normal Variation

“Bipolar disorder and schizophrenia, and many other types of mental illness, are diseases of the brain and should be treated and studied as such,” say Johns Hopkins researchers.

Photo by DESIGNECOLOGIST

Does this statement seem a bit obvious and not exactly rocket science? Although it may, this isn’t how the National Institute of Mental Health (NIMH) — the psychiatry wing of the National Institutes of Health — currently views severe mental disorders such as schizophrenia, autism, bipolar disorder and dementia. The NIMH is the largest federal agency that provides research funding on mental disorders.

For the past decade, the NIMH has used a system called Research Domain Criteria (RDoC) to describe all mental illnesses as dimensions of psychological norms that fall along extremes of too much or too little of common personality traits. For example, everyone has minor fears of things such as spiders, heights or snakes. But, having very strong or unmanageable fears might constitute an anxiety disorder.

While this way of thinking may make sense for anxiety, Johns Hopkins physicians argue that for the most severe of mental disorders — such as autism, schizophrenia or bipolar disorder — the approach will lead clinicians and scientists in the wrong direction. These conditions aren’t the result of too much or too little of a normal human trait. Rather they represent a clear-cut shift outside the typical dimensions of human experience.

In every other field of medicine, researchers use animal models of diseases based on genes and their interactions that contribute to disease risk. However, the current NIMH approach directs psychiatric researchers to focus on normal variation. Research on animal models with genetic variations that increase the risk of diseases often doesn’t get funded, they say.

The researchers lay out their thoughts in two commentaries, both published in Molecular Neuropsychiatry, one published in 2018 and the other in the October 2019 issue.

In their first commentary, the researchers argue that the NIMH approach of thinking of mental illness in dimensional terms is like regressing back to Galen’s Humors of the second century, when all illnesses were attributed to the imbalance of one of the four humors: yellow bile, black bile, blood and phlegm. Then, they argue that a biomedical approach using the tools of genetics, neuroscience and imaging can lead to rational targets for therapies. The second commentary is a point-by-point critique of the NIMH system and its flaws. They say that the RDoC system moves away from the proven power of biomedical research, which explores the causes of diseases and their effects on human biology. They add that the RDoC system doesn’t appropriately address the natural history or progression of a disease.

“Using the RDoC system hasn’t advanced the field of psychiatry, diverts attention from achieving an understanding of underlying mechanisms and ultimately delays discovering rational treatments for these diseases,” says author Christopher A. Ross, M.D., Ph.D., professor of psychiatry, neurology, neuroscience and pharmacology at the Johns Hopkins University School of Medicine.

This change in how the NIMH approaches mental illnesses occurred about a decade ago. Leadership at the NIMH initiated the RDoC system with the best motives in mind, in order to encourage neuroscience research to study how cells communicate with one another in the brain. However, this change to the RDoC system happened before modern genetic and other techniques pointed toward specific causes of major mental illnesses.

“No other NIH institute has adopted a scheme so discordant from modern biomedical research practice,” says Ross.

“The NIMH strategy makes psychiatry — and especially psychiatric research — seem like a strange and esoteric endeavor, not part of mainstream biomedicine, with the consequence of stigmatizing the entire discipline, including its patients,” says co-author Russell Margolis, M.D., a professor of psychiatry and neurology at Johns Hopkins.

Now that investigators have identified some genetic and environmental causes, and are beginning to reveal molecular mechanisms behind these disorders, the researchers say that it’s time for the NIMH to readjust their system. These changes should allow for conditions such as autism, bipolar disorder and schizophrenia to be researched and treated as diseases — and not as fringe versions of normal variation. Moving toward a system that values the biomedical approach, comparable with the other NIH institutes, they say, would guide the NIMH to support studies on mechanisms of disease, so researchers can design more targeted therapies for those with different forms of these illnesses. As psychiatric genetics is complex, so are the genetics of many common medical diseases, such as diabetes and rheumatoid arthritis. Nevertheless, in other fields, scientists successfully use modern biomedical technique to address complex diseases. The authors contend that the field of psychiatry and patients with severe mental diseases deserve no less.

Ross received research support from JNJ/Janssen, Teva, Raptor/Horizon, Vaccinex, uniQure and Roche/Genentech unrelated to these publications, and has consulted for Teva, Sage, uniQure, Roche/Ionis, Azevan, Annexon and the Healthcare Services Group. Margolis received grant support from Teva unrelated to the publications discussed here.

Social Interaction Difficulties in Autism

Study Challenges Assumptions About Social Interaction Difficulties in Autism

Photo by Sharon McCutcheon on Pexels.com

Autism is characterized in part by an individual’s challenges communicating and interacting socially with others. These difficulties have typically been studied in isolation by focusing on cognitive and behavioral differences in those with autism spectrum disorder, but little work has been done on how exchanges for autistic people unfold in the real world.

Researchers at The University of Texas at Dallas recently turned the spotlight on social interaction in autism by examining it as a two-way street. Their results, published in December in the journal Autism, suggest that successful interactions for autistic adults revolve around partner compatibility and not just the skill set of either person.

“Most studies attempting to understand social disability in autism focus exclusively on individual characteristics,” said Dr. Noah Sasson, an associate professor in the School of Behavioral and Brain Sciences (BBS) and corresponding author of the study. “This presumes that any difficulties in social interaction are driven solely by the autistic person. But how each person influences and is influenced by the other is key to understanding affiliation and social quality.”

The study focused on the so-called “double-empathy problem,” which predicts that two people who are neurologically different and have distinct modes of communication and understanding may have trouble connecting with each other, as commonly occurs in interactions between autistic and non-autistic adults.

Photo by Creative Vix on Pexels.com
Photo by Pixabay on Pexels.com

“It’s not just that autistic adults can struggle to infer the thoughts and motivations of typically developing adults, which has been well documented; the reverse is true as well. Non-autistic people struggle to infer what autistic people are thinking,” Sasson said. “Anecdotally, many autistic people often report better quality of social interaction when engaging with other autistic people. We set out to test this empirically.”

Kerrianne Morrison MS’16, PhD’19, the paper’s lead author, explained that the concept of a social-interaction difficulty being a two-sided, relational problem — and not simply a shortcoming of the autistic person — is only beginning to take hold.

“Autism is such a young field of study. Examining differences depending on the context of social situations rather than dysfunction across all contexts is starting to gain traction in academia,” she said. “We believe this represents a better understanding of how people with autism can thrive in the right contexts.”

In the study, 125 adults held a five-minute, unstructured “getting-to-know-you” conversation with an unfamiliar person. Sixty-seven of the participants had been diagnosed with autism. Each participant then independently evaluated the quality of the interaction and their first impressions of their partner.

Photo by Pixabay on Pexels.com

Autistic adults were not rated as less intelligent, trustworthy or likable by either the autistic or typically developing cohort, and importantly, autistic participants’ interactions with other autistic adults were viewed by them as more favorable than those with typically developing partners.

“While typically developing participants preferred future interaction with other typically developing partners over autistic partners,” Sasson said, “autistic adults actually trended toward the opposite, preferring future interaction with other autistic adults. They also disclosed more about themselves to autistic partners and felt closer to their partners than did typically developing participants.”

Autistic adults were rated as more awkward and less socially warm than typically developing adults by both autistic and typically developing partners. Some judgments were more favorable than those from Sasson’s previous studies in which people evaluated autistic adults in videos.

“Direct interaction seems to lessen some negative evaluations of autism,” Sasson said. “This aligns with previous work suggesting that direct experience and knowledge of autism can reduce stigma and promote inclusion.”

Typically developing participants also rated the conversational content with autistic and typically developing partners to be of similar quality. This shows that negative evaluations of autistic adults by non-autistic adults may be based more on social presentation differences and not their actual conversations.

“These findings suggest that social interaction difficulties in autism are not an absolute characteristic of the individual,” Sasson said. “Rather, social quality is a relational characteristic that depends upon the fit between the person and the social environment. If autistic people were inherently poor at social interaction, you’d expect an interaction between two autistic people to be even more of a struggle than between an autistic and non-autistic person. But that’s not what we found.”

Sasson said that he hopes this work shows that studying actual social interaction elicits a deeper understanding than studying individual abilities alone.

“Social disability in autism is context-dependent and emerges more in interactions with typically developing partners,” he said. “This likely reflects a mismatch in cognitive and communication styles that may improve with increased familiarity and acceptance.”

Morrison believes that this research is illuminating a crucial portion of the story for the autistic community.

Photo by Lukas on Pexels.com

“We’re moving beyond the existing research, which has fixated on social abilities in isolated, standardized contexts, and addressing this blind spot of real-world outcomes,” she said. “Particularly in adults, this is the information we need.”

Other authors affiliated with the School of Behavioral and Brain Sciences include Dr. Robert Ackerman, associate professor of psychology; cognition and neuroscience doctoral student Kilee DeBrabander; and psychological sciences doctoral student Desi Jones. Daniel Faso PhD’16 is also an author.

The work was funded by the Texas Higher Education Coordinating Board’s Autism Grant Program and internal funding.

Autism Diagnosis Test Needs Improvement

Photo by Porapak Apichodilok on Pexels.com

Study finds inconsistencies in a broadly used autism test

Rutgers researchers have found that a test widely used to diagnose whether children have autism is less reliable than previously assumed.

The study is published in the journal Neural Computation.

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 results showed that switching clinicians may change a child’s scores and consequently influences the diagnosis. The researchers found similar results when they analyzed open-access data of 1,324 people ages 5 to 65, said Elizabeth Torres, associate professor of psychology in Rutgers’ School of Arts and Sciences, and director of The New Jersey Autism Center of Excellence.

“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.

Devastating genetic disorder

Helping the world understand, detect and treat a devastating genetic disorder

Photo by Pixabay on Pexels.com

Fragile X syndrome may be a debilitating genetic neurodevelopmental disorder that affects people worldwide, but many doctors don’t know anything about it, including have the resources to properly diagnose or treat it.

The UC Davis MIND Institute is home to many of the world’s leading experts in fragile X syndrome and works globally to teach clinicians and families on the way to identify, test and supply look after those born with the disorder, often related to autism.

This multimedia story documents one such outreach effort in Serbia and therefore the lives of the Cvijetic family and their look for help for his or her 6-year-old son, Demetrije. Diagnosed with fragile X syndrome through the efforts of a MIND Institute-trained physician, the affectionate boy has never attended school, cannot speak or feed himself with a spoon or fork. His parents desperately hope he can someday have a productive life.

MIND Institute experts in fragile X syndrome are available for media interviews about their international work and ongoing research. They include:

Randi Hagerman, a pediatrician and professor at UC Davis, and one among the world’s leading experts on fragile X syndrome and related conditions and their treatment.

Leonard Abbeduto, a psychologist and director of the UC Davis MIND Institute who is internationally renowned for his work on the event and use of language in individuals with intellectual disabilities, including those with fragile X syndrome.

David Hessl, a toddler psychotherapist and professor at UC Davis whose expertise include the cognitive, emotional and behavioral evaluation of youngsters with fragile X syndrome.

The MIND Institute will next bring their expertise to Cartagena, Colombia for the Pan-American Conference of Neurodevelopment: Autism and Fragile X Syndrome, April 16-17 then to Quito, Ecuador for an additional conference April 20-21.

Signs of Autism

Levels of autism in China

Photo by Pixabay on Pexels.com

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.

New Policy Reduces Anti-Psychotic Medications in Foster Children

Photo by Michał Parzuchowski

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.”