TAG: "Autism"

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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SSRI use during pregnancy associated with risk of autism in boys


Highest association found during first-trimester exposure for autism.

Irva Hertz-Picciotto, UC Davis

Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), medications frequently prescribed to treat depression, anxiety and other mental health disorders, is associated with a higher incidence of autism spectrum disorder (ASD) and developmental delays (DD) in male children, a study of nearly 1,000 mother-child pairs has found.

Published online today (April 14) in the journal Pediatrics, the study involved 966 mother-child pairs from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, a population-based, case-control study at the UC Davis MIND Institute led by professor Irva Hertz-Picciotto, chief of the Division of Environmental and Occupational Health in the UC Davis Department of Public Health Sciences.

“This study provides further evidence that in some children, prenatal exposure to SSRIs may influence their risk for developing an autism spectrum disorder,” Hertz-Picciotto said. “It also highlights the challenge for women and their physicians, to balance the risks vs. benefits from taking these medications, given that a mother’s underlying mental health conditions may also pose a risk to both herself and her child.”

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Researchers uncover new aspect of autism


Splice variants reveal connections among autism genes.

Splicing variants (red) of autism genes were cloned from the brain and screened for interactions. The image on the right represents the network of interactions. Gray lines are interactions from a single isoform; red lines are interactions from additional isoforms of autism candidate genes (yellow circles).

A team of researchers from the UC San Diego School of Medicine and the Center for Cancer Systems Biology (CCSB) at the Dana-Farber Cancer Institute has uncovered a new aspect of autism, revealing that proteins involved in autism interact with many more partners than previously known. These interactions had not been detected earlier because they involve alternatively spliced forms of autism genes found in the brain.

In their study, published in the April 11 online issue of Nature Communications, the scientists isolated hundreds of new variants of autism genes from the human brain, and then screened their protein products against thousands of other proteins to identify interacting partners. Proteins produced by alternatively-spliced autism genes and their many partners formed a biological network that produced an unprecedented view of how autism genes are connected.

“When the newly discovered splice forms of autism genes were added to the network, the total number of interactions doubled,” said principal investigator Lilia Iakoucheva, Ph.D., assistant professor in the Department of Psychiatry at UC San Diego. In some cases, the splice forms interacted with a completely different set of proteins. “What we see from this network is that different variants of the same protein could alter the wiring of the entire system,” Iakoucheva said.

“This is the first proteome-scale interaction network to incorporate alternative splice forms,” noted Marc Vidal, Ph.D., CCSB director and a co-investigator on the study. “The fact that protein variants produce such diverse patterns of interactions is exciting and quite unexpected.”

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Study shows evidence that autism begins during pregnancy


Finding gives insight into the nature of autism.

Eric Courchesne, UC San Diego

Researchers at the UC San Diego School of Medicine and the Allen Institute for Brain Science have published a study that gives clear and direct new evidence that autism begins during pregnancy.

The study will be published in the March 27 online edition of the New England Journal of Medicine.

The researchers – Eric Courchesne, Ph.D., professor of neurosciences and director of the Autism Center of Excellence at UC San Diego; Ed S. Lein, Ph.D., of the Allen Institute for Brain Science in Seattle; and first author Rich Stoner, Ph.D., of the UC San Diego Autism Center of Excellence – analyzed 25 genes in post-mortem brain tissue of children with and without autism. These included genes that serve as biomarkers for brain cell types in different layers of the cortex, genes implicated in autism and several control genes.

“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” Courchesne said. “We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.” Stoner created the first three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern.

“The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder,” explained Lein.

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Atypical development in siblings of kids with autism can be seen at 12 months


Close to half of younger siblings of children with autism develop atypically, study finds.

UC Davis MIND Institute researcher Sally Ozonoff (right) working with a family

Atypical development can be detected as early as 12 months of age among the siblings of children with autism spectrum disorder, a study published by researchers with the UC Davis MIND Institute and UCLA has found.

Published online in the Journal of the American Academy of Child and Adolescent Psychiatry, the study found that close to half of the younger siblings of children with autism spectrum disorder (ASD) develop in an atypical fashion, with 17 percent developing ASD and another 28 percent showing delays in other areas of development or behavior.

Among the 28 percent of children with older siblings with ASD who showed delays in other areas of development, differences were identified in their social, communication, cognitive or motor development by 12 months. The most common deficits were in the social-communication domain, such as extreme shyness with unfamiliar people, lower levels of eye contact and delayed pointing.

The research suggests that parents and clinicians should be vigilant for such symptoms early on among the siblings of children with autism, in order to take full advantage of opportunities for targeted early intervention to improve those children’s outcomes.

“Having a child in the family with autism spectrum disorder means that subsequent infants born into that family should be regularly screened for developmental and behavioral problems by their pediatricians,” said Sally Ozonoff, study lead author and professor of psychiatry and behavioral sciences at the UC Davis MIND Institute.

“This research should give parents and clinicians hope that clinical symptoms of atypical development can be picked up earlier, so that we can, perhaps, reduce some of the difficulties that these families often face by intervening earlier.”

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