TAG: "Autism"

UC autism summit offers hope for help


First step toward collaborating systemwide to address need for treatments.

Leonard Abbeduto, director of the UC Davis MIND Institute, speaks at the UC summit on autism in Sacramento. (Photo by UC Davis)

By Alec Rosenberg

Researchers from across the University of California convened Thursday (Aug. 14) for a first-ever summit on autism — an initial step toward collaborating systemwide to address the urgent need for treatments.

Epidemiologists and geneticists joined neuroscientists and psychiatrists as more than 50 researchers from five UC campuses participated in the daylong summit at the UC Davis MIND Institute in Sacramento. They shared what they are doing in autism research and discussed ways to increase coordination and have a greater impact in improving the lives of children with autism and their families.

Autism spectrum disorder is one of health’s toughest challenges — a lifelong developmental condition with varying symptoms and severity that can affect social interactions, behavior and the ability to think, learn and problem solve. It has no single known cause and no known cure, though early behavioral-based treatments can help. And its prevalence is rising rapidly: Estimates are that autism affects more than 3 million individuals in the U.S., increasing the need for breakthroughs.

“How can we provide high-quality care for kids when the numbers are increasing dramatically and the resources are not?” said Leonard Abbeduto, Tsakopoulos-Vismara Endowed Chair and director of the UC Davis MIND Institute. “We’re all here because we want to impact the lives of kids and families.”

The autism summit, sponsored by the UC Office of the President, is the first step in an 18-month process aimed at accelerating progress toward treatments and strategies for prevention. The effort will include drafting a strategic plan for a coordinated approach to UC autism research, identifying research opportunities, increasing the number of multicampus grants and launching a series of public statewide autism forums to discuss ways of translating research into improved services.

“These are ambitious goals, but this is the group to make it happen,” Abbeduto said.

Harnessing UC’s expertise

The campuses participating in the summit — Davis, Irvine, UCLA, San Diego and San Francisco — are those with interdisciplinary autism research programs, integrated health care systems and programs that train pediatric health care professionals. Other UC campuses will participate in follow-up meetings.

The summit arose from discussions within the systemwide UC BRAID (Biomedical Research Acceleration, Integration and Development), which identified autism as an area of expertise that was ripe for increased coordination.

“This is really the beginning,” said Dan Cooper, chair of the Department of Pediatrics and director of the Institute for Clinical and Translational Science at UC Irvine. “The summit is designed to harness the unique basic science and translational research talent across the UC system in a way that will profoundly benefit children and adults with autism and related disorders.”

As one of the world’s largest and most prestigious research institutions, UC is uniquely positioned to address the mysteries surrounding autism.

“If we combine and band together, the promise is tremendous,” said Elysa Marco, a cognitive and behavioral child neurologist at UC San Francisco. “I think this represents a wonderful opportunity for us to do something greater.”

A timely collaboration

Thomas Insel, director of the National Institute of Mental Health, who delivered a summit presentation by videoconference, encouraged UC’s efforts, which he said could be a model at the statewide level.

“If you can get a group of people across the state sharing things, that’s a great way to accelerate our understanding and development of treatments,” said neurologist Jeffrey Neul of UC San Diego.

Autism is considered a public health crisis, with an incidence that has increased by more than 600 percent during the past two decades. The U.S. Centers for Disease Control and Prevention estimates that autism now affects 1 in 68 children. More than 350,000 Californians live with autism today.

Los Angeles Unified School District alone has 10,000 students with autism, said James McCracken, the Joseph Campbell Professor of Child Psychiatry and director of the Division of Child and Adolescent Psychiatry at UCLA. He’s optimistic that the UC autism summit will lead to positive outcomes.

“It’s an exciting first step,” McCracken said.

Making an impact

At the summit, researchers split into six working groups aimed at tackling different aspects of autism: genetic risk factors; environmental risk factors; neurobiology; diagnosis, symptoms and developmental trajectories; treatment, pharmacology and services; and research infrastructure.

They identified opportunities for collaboration such as multicampus research projects, hosting workshops to share data and provide training, and developing a systemwide autism patient registry and research repository. They encouraged using the UC ReX (Research eXchange) Data Explorer, a UC BRAID effort that enables UC investigators to identify potential research study cohorts at the five UC medical centers. Several mentioned that offering incentives would spur broader collaborations.

Ultimately, UC summit participants want to help prevent autism and speed treatments and cures. They’re working on many fronts, from behavior to medications to stem cells.

UC Davis MIND Institute researcher Sally Rogers helped develop the Early Start Denver Model, an intensive early intervention therapy for children with autism that fuses play- and relationship-based approaches with teaching practices of applied behavior analysis (a model developed at UCLA).

The Early Start Denver Model is being used around the world. Last week, Rogers trained a group that included participants from Brazil, Canada, Mexico, Spain and Turkey. She wants to have an even bigger impact and sees potential in a universitywide autism collaboration.

“It’s about trying to enhance the quality of life,” Rogers said.

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UC Davis researchers launch study examining autism in girls


Little is known about biological differences between boys and girls with autism.

Little is known about autism in girls.

Autism is far more common in boys than girls – affecting 1 in 54 boys and 1 in 252 girls — but little is known about biological differences between boys and girls with autism. A new study, called the ‘Girls with Autism — Imaging of Neurodevelopment’ or GAIN Study, led by researchers at the UC Davis MIND Institute will explore those differences in very young girls with autism.

“We know that the incidence of autism is much lower in girls than it is in boys. But we don’t know much about why that is, and what those differences are,” said Christine Wu Nordahl, assistant professor of psychiatry and behavioral sciences and principal investigator for the study. “Because autism so much more common in boys, girls are often understudied, and we haven’t had the chance to evaluate them in depth.”

To investigate the differences between autism in boys and autism in girls, MIND Institute researchers are seeking very young girls with autism — between the ages of 2 and 3.5 years old — who are recently diagnosed with autism. The researchers also are enrolling girls in the same age range who are developing typically.

Study participants will be followed for two years and will receive magnetic resonance imaging (MRI) scans and other tests, to help researchers identify differences in brain structure and connectivity between boys and girls with autism.

“A comprehensive understanding of the female phenotype of autism spectrum disorder is a pressing and timely topic, as indicated by national efforts to direct research towards this goal,” Wu Nordahl said.

For further information about the research or to inquire about enrolling a child in the study, please contact Michelle Huynh, study coordinator, at (916) 703-0410, or michelle.huynh@ucdmc.ucdavis.edu.

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UC hosting statewide autism summit


UC researchers collaborate across system to address urgent need for treatments.

Bringing together the research prowess of the University of California to address the increase in autism incidence, its public health impacts, and the need to speed the development of treatments for affected individuals and their families, internationally respected scientists from UC campuses at Irvine, Los Angeles, San Diego, San Francisco and Davis will converge at the UC Davis MIND Institute for a daylong summit on innovative translational neurodevelopmental research.

An initiative of the UC Office of the President, the University of California Summit on Translational Research in Autism Spectrum Disorders will be held Thursday (Aug. 14) from 8 a.m. to 5 p.m. at the UC Davis MIND Institute, 2825 50th St., Sacramento. The summit will include a presentation via video conference on “Pressing Issues for a Translational Science of Autism Spectrum Disorder” by Thomas Insel, director of the National Institute of Mental Health (NIMH). Participation in the summit is by invitation only.

“The increase in autism spectrum disorder cases has exceeded the capacity of public and private organizations to provide effective health care, education and treatment to affected families,” said Leonard Abbeduto, Vismara-Tsakopoulos Endowed Chair and director of the MIND Institute.

“We must develop new, more effective strategies for treatment and prevention that are informed by a deeper understanding of the etiology, mechanisms and manifestations of the disorder.”

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Kids with autism, SPD show brain wiring differences


UCSF study builds on its research showing kids with SPD have measurable brain differences.

Pratik Mukherjee, UC San Francisco

Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.

The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, M.D., Ph.D., a professor of radiology and biomedical imaging and bioengineering at UCSF.

SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

Elysa Marco, UC San Francisco

“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, M.D., cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.

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Study links autistic behaviors to enzyme


Deleting the enzyme favorably impacts behaviors associated with fragile X syndrome.

Iryna Ethell, UC Riverside (Photo by L. Duka)

Fragile X syndrome (FXS) is a genetic disorder that causes obsessive-compulsive and repetitive behaviors, and other behaviors on the autistic spectrum, as well as cognitive deficits. It is the most common inherited cause of mental impairment and the most common cause of autism.

Now biomedical scientists at UC Riverside have published a study that sheds light on the cause of autistic behaviors in FXS. Appearing online today (July 23) in the Journal of Neuroscience, and highlighted also on the cover in this week’s print issue of the journal, the study describes how MMP-9, an enzyme, plays a critical role in the development of autistic behaviors and synapse irregularities, with potential implications for other autistic spectrum disorders.

MMP-9 is produced by brain cells. Inactive, it is secreted into the spaces between cells of the brain, where it awaits activation. Normal brains have quite a bit of inactive MMP-9, and the activation of small amounts has significant effects on the connections between neurons, called synapses. Too much MMP-9 activity causes synapses in the brain to become unstable, leading to functional deficits.

“Our study targets MMP-9 as a potential therapeutic target in fragile X and shows that genetic deletion of MMP-9 favorably impacts key aspects of FXS-associated anatomical alterations and behaviors in a mouse model of fragile X,” said Iryna Ethell, a professor of biomedical sciences in the UC Riverside School of Medicine, who co-led the study. “We found that too much MMP-9 activity causes synapses to become unstable, which leads to functional deficits that depend on where in the brain that occurs.”

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Personalized approach enhances communications skills in children with autism


Computer tablets play key role in the blended therapy, UCLA-led study finds.

Connie Kasari, UCLA

A UCLA-led study has found that the communication skills of minimally verbal children with autism can be greatly improved through personalized interventions that are combined with the use of computer tablets.

The three-year study examined different approaches to improving communication abilities among children with autism spectrum disorder and minimal verbal skills. Approximately 30 percent of children with ASD overall remain minimally verbal even after years of intervention.

UCLA professor Connie Kasari, the paper’s senior author, worked with researchers at Vanderbilt University and the Kennedy Krieger Institute. They found that children’s language skills greatly improved when spoken- and social-communication therapy was tailored based on their individual progress and delivered using computer tablets.

The trial involved 61 children with ASD, ages 5 to 8. For six months, each child received communication therapy focusing on social communication gestures, such as pointing, as well as play skills and spoken language.

Half of the children were randomly selected to also use speech-generating applications on computer tablets for at least half of the time during their sessions. The tablets were programmed with audio clips of words the children were learning about during their therapy sessions and images of the corresponding objects. Working with a therapist, the child could tap a picture of a block, for example, and the tablet would play audio of the word “block.”

The researchers found that children who had access to the tablets during therapy were more likely to use language spontaneously and socially than the children who received the communication intervention alone — and that incorporating the tablets at the beginning of the treatment was more effective than introducing it later in the therapy.

“It was remarkable how well the tablet worked in providing access to communication for these children,” said Kasari, professor of human development and psychology in the UCLA Graduate School of Education and professor of psychiatry at UCLA’s Semel Institute for Neuroscience and Human Behavior. “Children who received the behavioral intervention along with the tablet to support their communication attempts made much faster progress in learning to communicate, and especially in using spoken language.”

Researchers also conducted follow-up visits with the children three months after the initial study period and found that their improvement had been maintained during that time.

The study was the first ASD research to use a sequential multiple assignment randomized trial, or SMART, design. The approach, which enables researchers to tailor interventions according to how each child in the study responds, was designed by Daniel Almirall and Susan Murphy, biostatisticians at the University of Michigan who were members of the research team. It also was the first randomized, controlled trial on this underserved population of children to use a computer tablet combined with an effective behavioral intervention.

Other study authors were Rebecca Landa of Kennedy Krieger and Johns Hopkins University, and Ann Kaiser of Vanderbilt. The study was funded by a High Risk High Impact grant from the Autism Speaks Foundation.

The findings were published in the June issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Based on this study, Kasari, who also is a member of UCLA’s Center for Autism Research and Treatment, received a $13 million grant from the National Institutes of Health’s Autism Centers of Excellence to fund continued research involving minimally verbal children.

The ACE Network–funded research, which is now under way, compares two types of intensive, daily instruction for children who attend schools in underserved communities and have an autism spectrum disorder and minimal communication abilities. The study also uses a SMART design and computer tablets. Researchers on the five-year network study are enrolling nearly 200 children at UCLA, Weill Cornell Medical Center in New York City, the University of Rochester and Vanderbilt University in Nashville.

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UC Davis professor receives award to develop preventive treatment for autism


Research seeks to prevent maternal antibody-related autism.

Judy Van de Water, UC Davis

The Hartwell Foundation has presented an Individual Biomedical Research Award to professor Judy A. Van de Water of UC Davis, recognizing research that could affect nearly one in every four cases of autism among children in the U.S.

Van de Water, an immunologist and professor of internal medicine in the UC Davis School of Medicine, is one of 11 scientists from throughout the U.S. selected to receive the award that recognizes early-stage, innovative and leading-edge biomedical research with the potential to benefit children in the United States.

Van de Water is an autism researcher affiliated with the UC Davis MIND Institute. She is the eighth UC Davis researcher selected for the honor since 2008. Awardees receive $100,000 direct costs each year for three years.

In 2013, Van de Water described how unique antibodies in the bloodstream of some pregnant mothers target proteins critical to the fetal brain development. The discovery represents the first definitive cause for a subset of cases of non-genetic causes of autism. Van de Water coined the term maternal autoantibody-related (MAR) autism to describe the 23 percent of autism cases associated with maternal autoantibodies.

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First pediatric autism study conducted entirely online


UCSF shows success of randomized clinical trial for kids with autism.

UC San Francisco researchers have completed the first Internet-based clinical trial for children with autism, establishing it as a viable and cost effective method of conducting high-quality and rapid clinical trials in this population.

In their study, published in the June issue of the Journal of the American Academy of Child and Adolescent Psychiatry, the researchers looked at whether an Internet-based trial was a feasible way to evaluate whether omega-3 fatty acids helped reduce hyperactivity in children with autism. The authors found that not only was it a valuable platform for conducting the randomized clinical trial, but that it was both cost and time effective, as well.

“Recruitment for clinical trials in children with autism is one of the biggest challenges we face in studying potential treatments, and we found that process to be accelerated and streamlined by using existing online communities for enrollment,” said lead author Stephen Bent, associate professor of medicine at UCSF. “This trial can serve as a model for how to efficiently test potential treatments through the growing power of online communities.”

Using the Interactive Autism Network’s (IAN) robust online community of parents, the researchers enrolled 57 children from 28 states into the randomized trial.

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Mother’s place of birth is a risk factor for autism in U.S.-born children


Risk varies by race and ethnicity.

Beate Ritz, UCLA

Can the place where a woman is born and raised be a risk factor for autism in her child? According to new research out of UCLA, the answer is yes.

In the U.S., the prevalence of autism has been reported to be highest among non-Hispanic white children, but a new study from the UCLA Fielding School of Public Health offers evidence that other ethnic groups actually are at a higher risk for the disorder. Using data from racially diverse Los Angeles County, which is home to a large number of recent immigrants, the researchers found that the mother’s place of birth is a risk factor for autism among U.S. children.

Specifically, they found that when compared with children born to white American mothers, children of foreign-born women who are black, Central or South American, Filipino and Vietnamese had a higher risk of autism. The same held true for children of U.S.-born African American and Hispanic women. The risks were adjusted for maternal age, education levels, socioeconomic status, whether the families had health insurance and other factors known to influence the diagnosis rate.

The study appears in the current online edition of the journal Pediatrics.

Autism spectrum disorders are complex developmental disorders that affect how a person behaves, interacts with others, communicates and learns. Until now, though, scientists have had a difficult time determining possible prenatal risk factors other than the mother’s age and complications during pregnancy. However, recent European studies have reported an association between the nation where a woman is born and her children’s risk for autism.

“Epidemiology has a long tradition of using migration studies to understand how environmental and genetic factors contribute to disease risk in populations,” said Dr. Beate Ritz, the paper’s senior author, and a professor and chair of the Fielding school’s Department of Epidemiology. The fact that 22 percent of 6-year-olds born in the United States have immigrant parents opened a unique opportunity for us to consider the influence of nativity, race and ethnicity on the causes of autism spectrum disorder.”

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Study finds association between pesticides, autism


Maternal exposure to agricultural pesticides tied to increased risk of autism in offspring.

Janie Shelton, UC Davis

Pregnant women who lived in close proximity to fields and farms where chemical pesticides were applied experienced a two-thirds increased risk of having a child with autism spectrum disorder or other developmental delay, a study by researchers with the UC Davis MIND Institute has found. The associations were stronger when the exposures occurred during the second and third trimesters of the women’s pregnancies.

The large, multisite California-based study examined associations between specific classes of pesticides, including organophosphates, pyrethroids and carbamates, applied during the study participants’ pregnancies and later diagnoses of autism and developmental delay in their offspring. It is published online today (June 22) in Environmental Health Perspectives.

“This study validates the results of earlier research that has reported associations between having a child with autism and prenatal exposure to agricultural chemicals in California,” said lead study author Janie F. Shelton, a UC Davis graduate student who now consults with the United Nations. “While we still must investigate whether certain subgroups are more vulnerable to exposures to these compounds than others, the message is very clear: Women who are pregnant should take special care to avoid contact with agricultural chemicals whenever possible.”

California is the top agricultural producing state in the nation, grossing $38 billion in revenue from farm crops in 2010. Statewide, approximately 200 million pounds of active pesticides are applied each year, most of it in the Central Valley, north to the Sacramento Valley and south to the Imperial Valley on the California-Mexico border. While pesticides are critical for the modern agriculture industry, certain commonly used pesticides are neurotoxic and may pose threats to brain development during gestation, potentially resulting in developmental delay or autism.

The study was conducted by examining commercial pesticide application using the California Pesticide Use Report and linking the data to the residential addresses of approximately 1,000 participants in the Northern California-based Childhood Risk of Autism from Genetics and the Environment (CHARGE) Study. The study includes families with children between 2 and 5 diagnosed with autism or developmental delay or with typical development. It is led by principal investigator Irva Hertz-Picciotto, a MIND Institute researcher and professor and vice chair of the Department of Public Health Sciences at UC Davis. The majority of study participants live in the Sacramento Valley, Central Valley and the greater San Francisco Bay Area.

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Families with an autistic child are a third less likely to have more kids


UCSF study has implications for studying the genetic basis and risk of the disorder.

Neil Risch, UC San Francisco

Parents who have a child with autism spectrum disorder (ASD) are about one-third less likely to have more children than families without an affected child, according to a study led by a UC San Francisco researcher.

The findings, which appear in today’s (June 18) issue of JAMA Psychiatry, stem from the largest study of its kind on further child bearing after a child has been diagnosed with the disorder. These are the first data to indicate that this is a reproductive decision. “While it has been postulated that parents who have a child with ASD may be reluctant to have more children, this is first time that anyone has analyzed the question with hard numbers,” said Neil Risch, Ph.D., a UCSF professor of epidemiology and biostatistics and director of the UCSF Institute for Human Genetics.

Most previous research into the heredity of autism has ignored a possible decision on the part of parents with affected children to reduce their subsequent child-bearing, a situation that occurs with some birth defects and has been termed “reproductive stoppage.” As a result, previous estimates of the odds of having a second child with the disorder may have made the risk appear lower than it actually is.

“This study is the first to provide convincing statistical evidence that reproductive stoppage exists and should be taken into account when calculating the risks for having a another child with ASD,” said Risch, who is senior author on the paper. “These findings have important implications for genetic counseling of affected families.”

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Autism-like symptoms reversed in mice


Old drug used for sleeping sickness may point to new treatment in humans.

Transmission electron micrograph of cell mitochondrion. (Image by Thomas Deerinck, UC San Diego)

In a further test of a novel theory that suggests autism is the consequence of abnormal cell communication, researchers at the UC San Diego School of Medicine report that an almost century-old drug approved for treating sleeping sickness also restores normal cellular signaling in a mouse model of autism, reversing symptoms of the neurological disorder in animals that were the human biological age equivalent of 30 years old.

The findings, published in today’s (June 17) online issue of Translational Psychiatry, follow up on similar research published last year by senior author Robert K. Naviaux, M.D., Ph.D., professor of medicine, pediatrics and pathology, and colleagues.

Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: “Twenty percent of the known factors associated with autism are genetic, but most are not. It’s wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact.  The net result of this interaction is metabolism.”

Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, said one of the universal symptoms of autism is metabolic disturbances. “Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them. These create a sort of chemical glow that broadcasts the state of health of the cell.”

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