Summaries of Funded Studies (Augmentation and Bridge)
“Augmentation” Grants Designed to Supplement or Expand the Scope of Existing Projects
In light of a tighter federal research budget, Autism Speaks initiated an “augmentation” funding mechanism designed to supplement or expand the scope of existing NIH and CDC-funded research projects.
The additional funds included in these research grants enhance the scientific value of the overall endeavor and capitalize on projects which are already underway. Autism Speaks invited proposals from all areas of basic and clinical research, including human behavior, neurobiology, genetics, immunology, endocrinology, molecular and cellular biology, and epidemiology.
The following represent projects which were carefully evaluated for their abilities to make a unique contribution to the field of autism research leveraging existing funding from other sources.
The specific aims of the projects listed below would not have been possible without Autism Speaks funding, which will allow these studies to continue past the time that their funding would have ended, or provide supplemental resources for additional studies to be conducted.
Out of 17 full proposals received, a total of 11 projects totaling $897,527 in topic areas including epidemiology, pharmaceutical treatment, language, and neuroscience were approved for funding.
All grant applications were reviewed and approved by the Autism Speaks Scientific Advisory Board together with a group of panel reviewers. Final recommendations were presented to and approved by the Autism Speaks Board of Directors on Dec. 7, 2006.
L. Eugene Arnold, M.D.
Ohio State University, OH
$97,659.00 for one year
Risperidone and Behavior Therapy in Children with Pervasive Developmental Disorder: Long Term Follow-up
Based on an earlier study by Dr. Arnold and his colleagues in the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network, the FDA recently approved the use of the antipsychotic drug risperidone to treat irritability and aggression in children with autism.
The Network—lead by Dr. Arnold at Ohio State and including teams from Yale University and Indiana University—are now working on an NIH-funded follow-up study. The new study will examine whether risperidone combined with parent management training (PMT) can boost the effectiveness of risperidone and help lower relapse rates once patients stop taking the medication. The research team will randomly assign 120 children with pervasive developmental delay (PDD) to either treatment with risperidone alone or risperidone plus PMT.
They will then evaluate autism-related behaviors. This grant will provide funding for a one-year follow up to examine the long-term effects of PMT and risperidone.
What this means for people with autism: Results from this study will provide clinicians with important information about the long-term effectiveness of combining drug therapy with parent training for treating aggression and irritability in children with autism. Since prolonged use of antipsychotic drugs poses some risks to children, it will be extremely helpful to examine whether parent training can help reduce the need for medication over time.
Lisa Croen, Ph.D.
Kaiser Permanente Division of Research, CA
$200,000.00 for one year
Augmentation of CA CADDRE Studies
Since 2001, the California Center for Autism and Developmental Disabilities Research and Epidemiology (CA CADDRE) has been one of the largest, most extensive datasets of information on children with autism living in California.
CA CADDRE, funded by the Centers for Disease Control and Prevention, is run collaboratively by Dr. Croen from Kaiser Permanente’s Division of Research and Drs. Grether and Windham from the Department of Health Services.
The CA CADDRE center has also used Kaiser Permanente medical records to investigate autism risk factors during pregnancy and early childhood.This grant will fund several new analyses of this rich dataset to examine risk factors for autism that have been speculated about in the literature.
For example, Dr. Croen and her colleagues will investigate the risk of autism from:prenatal exposure to the immunization RhoGAM, which is given to women who deliver a Rh+ baby;maternal illnesses such as infections, inflammation and endocrine disorders;maternal hormone use, ultrasound exams and maternal use of the asthma drug terbutaline;maternal exposure to environmental chemicals, including airborne chemicals and workplace exposure.
What this means for people with autism: Data from this study will fill important gaps in understanding environmental risk factors for autism spectrum disorders. Researchers will be able to use the results from these analyses to design future autism studies and, potentially, to design strategies to prevent autism spectrum disorders.
Joachim Hallmayer, M.D.
Stanford University Medical School
$99,913.00 total for one year
A California population-based twin study of autism
Over the past two decades, research has supported the idea that autism has a strong genetic component. The strongest evidence comes from studies of twins that show that identical twins have a 90 percent chance of sharing a diagnosis of autism.
Unfortunately, these studies have been too small to demonstrate the genetic risk for autism in fraternal twins. In addition, these studies have not been able to establish whether people with autism inherit susceptibility for a general diagnosis of autism or whether they inherit susceptibility for specific autism traits and behaviors.
This funding will provide additional support to Dr. Hallmayer’s group to conduct the largest, most detailed, population-based study of twins with autism, examining 300 pairs of twins across California. They will measure autistic-like behaviors; repetitive and stereotyped behaviors; general cognitive ability; and more specific neurocognitive abilities.
This funding will allow Dr. Hallmayer’s team to increase the number of twin pairs studied. In addition, it will allow them to measure social and communication abilities with the Social Responsiveness Scale and to collect additional blood samples from family members that can be used to search for specific genes.
Such a large sample, together with detailed assessments, will allow the researchers to verify earlier estimates about the heritability of autism. It will also help them tease apart which traits and symptoms of autism are genetic and which are more likely influenced by the environment.
What this means for people with autism: This study will not only vastly improve estimates of the heritability of autism, but will also allow researchers to determine which behavioral and cognitive traits are specific to autism, which are mostly determined by genes, and which are more influenced by the environment. Such data will help genetics researchers by providing them with unambiguous genetic subgroups in which to search for genes for specific traits.
James Sutcliffe, Ph.D.
$100,000 for one year
Altered regulation of the serotonin transporter is mediated by autism associated functional variation in beta3 integrin
It is becoming increasingly clear to researchers and clinicians that the neurotransmitter serotonin plays an important role in autism. Clinically, drugs that increase serotonin levels in autistic patients help to alleviate some symptoms of the disorder.
Molecular, genetic and clinical research demonstrates that variation in the serotonin transporter (SERT) are related to an increased risk of autism. However, the mechanism by which SERT activity is regulated is not well characterized.
Studies by Dr. Sutcliffe and others have begun to identify several mechanisms as well as possible genes that might lead to an increase in serotonin transporter activity.This study will build on NIH funded research that examines the role of SERT activity and autism spectrum disorders.
Specifically, Dr. Sutcliffe and his colleagues have found that a particular form of a protein named integrin beta3 is associated both with autism and with elevated SERT activity. The gene Leu33Pro (Pro 33) codes for this form of integrin beta3.
This grant will allow Dr. Sutcliffe’s team to build on their work by funding a program to create a gene “knock-in” mouse model, creating mice that carry the Pro33 variant of the integrin beta3 gene. The researchers will use this mouse model to study how the Pro33 variant of integrin beta3 affects SERT activity and serotonin levels in mice carrying this genetic mutation.
What this means for people with autism: Compounds which target the SERT receptor are currently used to treat autism; however, the mechanism by which serotonin activity is regulated through this receptor is not well described.
This study will allow researchers to better understand the mechanisms linking serotonin, the SERT receptor and autism. In particular, it will create a mouse model to tease apart how a variant of a gene for the protein integrin beta3 affects serotonin transporter activity.
Having such a model will allow the researchers to study the influence this gene has in development and, potentially, on pharmacological therapies.
Jane Charles, M.D. and Joyce Nicholas, Ph.D.
Medical University of South Carolina
$50,000.00 for one year
Enhancing Current Capacity for Surveillance of Autism Spectrum Disorders: 4 Year Old Surveillance
To better implement services and understand the scope of autism spectrum disorders (ASDs), researchers and service providers need an accurate count of how many people are affected by ASDs.
Since 2000 Drs. Charles and Nicholas, funded by the Centers for Disease Control and Prevention, have been monitoring rates of ASDs in 8-year-olds in South Carolina.
Their research has found that as many as 84 percent of children with ASDs showed some sign of developmental delay before age three. This study would allow the researchers to expand their surveillance of ASDs in South Carolina by also looking at rates of ASDs in four-year-olds.
The research team evaluates the rate of ASDs through a thorough examination of medical, school and public health records, including records from major medical centers and the South Carolina Department of Health and Environmental Control (DHEC).
This grant will allow them to expand their data sources to include those relevant to young children. In particular, they will examine records from the Medical University of South Carolina, which provides assessment and treatment services to children with developmental disabilities beginning at birth.
The investigators also have access to data from a program administered by DHEC called Babynet, which provides services for children zero to three.
What this means for people with autism: This project will provide important information about the number of young children with ASDs as well as how well service providers are executing early detection. This information can be used for planning and implementation of ASD-related services.
Daniel Goldowitz, Ph.D.
University of Tennessee Health Sciences Center
$100,000 for one year
A systems neurobiology approach in a model organism to understand the role of the cerebellum in autism.
In recent years researchers have found a connection between autism and damage to cells in an area of the brain called the cerebellum.
In particular, a loss of a kind of nerve cell called Purkinje cells appears to disrupt connections between the cerebellum and the prefrontal cortex, which controls higher brain functions such as learning and cognitive processing. Dr. Goldowitz and his team have theorized that this disruption may be one key to how autism spectrum disorders develop. They have conducted a long program of research to examine the role of Purkinje cell loss in autism using a mouse with a gene mutation called Lurcher which causes mice to loose all of their Purkinje cells in the first two to three weeks of life.
The researchers have also created a unique type of mouse in which individual mice loose variable numbers of Purkinje cells and show signs of behaviors similar to those of people with autism. Through funding from NIH, Dr. Goldowitz and his colleagues have begun a program to compare the molecular and anatomical differences between the development of normal and mutant mice.
This funding will allow Dr. Goldowitz and his team to expand their research to include a behavioral assessment of their theory. They will test their mice on an operant task that will measure how well the mice learn rules and process information. They will then determine the relationship between the absolute number of Purkinje cells a mouse has and any cognitive learning deficits detected through these tests.
What this means for people with autism:This study uses cutting edge technology in the form of a genetically modified mouse to discover how loss of Purkinje cells in the cerebellum during development may be responsible for cognitive and learning impairments in autism. This work will not only help researchers better understand how autism develops in people, but the mouse model may provide a tool for testing intervention strategies for treating autism.
Randy Hagerman, M.D.
M.I.N.D. Institute at the University of California at Davis
$50,000 for one year
Genotype-Phenotype Relationships in Fragile X Families
Fragile X syndrome (FXS) is the most common heritable form of mental retardation and is a frequent cause of autism. Specifically, up to 30 percent of people with FXS have autism and 2 to 8 percent of children with autism are also diagnosed with FXS.
Over the past several years Dr. Hagerman and his colleagues have found a more specific association between the two disorders. Their work indicates that people with a certain subtype of FXS, termed “fragile X premutation” are at increased risk for autism and attention deficit hyperactivity disorder.
In addition, these people show elevated levels of the genetic material that produces a protein called Fragile X Mental Retardation Protein—FMR1 mRNA. Increases in FMR1 mRNA in turn, correlate with emotional problems and a disruption in attending to social stimuli. Dr. Hagerman and his team speculate that FMR1 may prove toxic to brain systems and that then lead to autism in people with the premutation.This grant will provide bridge funding to compare twenty young men, between 8 and 16, with the premutation with 20 young men without the premutation.
Each subject will undergo a thorough evaluation for autism and ADHD, in addition to a molecular analysis for fragile X.
This study will allow Dr. Hagerman’s group to continue NIH-sponsored research at the MIND Institute to study whether autism in young males with the premutation is related to FMR1 mRNA toxicity.
What this means for people with autism:Due to the concordance of Fragile X Syndrome and autism, FXS is considered an excellent genetic model for autism spectrum disorders. In fact, the American Academy of Pediatrics recommends routine screening for FMR1 in the medical evaluation of autism.
It is likely that the pathways leading to autism in FXS are related to pathways that lead to other subgroups of autism. This study will allow Dr. Hagerman’s group to focus on the cause and consequences of a specific mutation of the Fragile X gene that causes an increase in FMR1 mRNA. The outcome will lead to better treatment interventions and pharmacotherapies both for FXS and autism.
Rebecca Landa, Ph.D.
Kennedy Krieger Research Institute
$50,000 for one year
Developing Diagnostic Criteria for Toddlers with ASD
Although autism spectrum disorder (ASD) appears to have its neurobiologic origins in prenatal or early postnatal life, it is not usually diagnosed before a child is three years old. In fact, there are no clinical guidelines for detecting ASD before 30 months.
Dr. Landa and her colleagues have begun a program of study to develop criteria for diagnosing ASD by 18 months. Their preliminary findings from an NIH-funded study to assess social, language, cognitive, motor, and adaptive development from 14 months to 30 or 36 months show promise in detecting ASD between 14 months and 18 months.
In particular, they find that measures of joint attention, shared positive mood and imitation help predict ASD. The researchers plan to corroborate their findings by almost doubling their sample size, adding 108 more children to the 125 they’ve already assessed. Their study compares three groups of children: siblings of children with ASD who are at increased genetic risk for the disorder, late talkers with no family risk of autism, and children with no family risk for ASD.
NIH is funding assessments of these children at 18 months and 30 months. This augmentation grant will allow the researchers to include assessments at 14, 24 and 36 months.
These more frequent assessments will provide a clearer picture of when detectable symptoms of ASD begin to manifest and whether the diagnosis is stable through age three. The researchers expect to replicate their earlier findings that they can diagnose ASD in some children by 14 months but not in others until later and that some children may show signs of ASD at 14 months but not at 36 months.
What this means for people with autism:Findings from this study will provide a concrete set of sensitive and specific criteria for diagnosing ASD in children between 14 and 18 months of age. These diagnostic criteria will provide clinicians with a research-based tool with which to assess the increasing number of children referred before age three for evaluation of possible ASD. Early diagnosis will in turn allow children to receive intervention at the earliest possible time.
Karla McGregor, Ph.D.
University of Iowa
$50,000 for one year
The Development of Word Meaning
A new theory of language learning has gained support over the past several years among psycholinguists and more general cognitive scientists.
The theory, called the emergentist coalition model (ECM), theorizes that children learn words by paying attention not only to the salience of the object being referred to but also to social cues such as the speaker’s gaze toward the object and syntactic cues such as word order.
Through NIH funding, augmented by this grant, Dr. McGregor and her colleagues hope to test ECM. They’re particularly interested in the less studied second phase of word learning, called “slow mapping,” when the brain begins to develop a more complex understanding of a word’s meaning and how it connects to other words.
Their study will take advantage of naturally occurring variations among children in their ability to process social cues and syntactic information. In particular, the researchers will compare three groups of children, ages 8 to 13: normally developing children; children with high functioning autism who are poor at processing social cues; and children with specific language impairment who are poor at processing syntactic information.
Comparing these groups of children will allow the researchers to determine whether syntactic and social cues are as important for slow mapping as they are for initial word learning. They will also provide a clearer understanding of language impairment among people with autism.
This augmentation grant will allow the researchers to expand their study to recruit children with both high functioning autism and specific language impairment. It will also allow them to conduct two new experiments to measure children’s knowledge of familiar nouns and verbs. These experiments will provide more detail about how the brain organizes words in these different groups of children.
What this means for people with autism: This research will lead to new information about word learning during slow mapping. It will also advance our understanding of the effect of autism spectrum disorders on language development and the nature of language impairment among people with ASD. Ultimately, this information could lead to more effective treatments for enhancing language learning.
Stewart Mostofsky, MD
Kennedy Krieger Research Institute
$50,000 for one year
Motor Skill Learning in Autism: Anatomic MRI AugmentationPeople with autism often have difficulty with various aspects of motor control, including complex motor skills and gestures. While measuring motor function is generally easier and more consistent than measuring other complex behaviors, including language and communication, little research has investigated motor learning in autism.
Using an NIH grant, Dr. Mostofsky and his team are measuring motor skill learning and motor imitation in children with autism. They are then using functional magnetic resonance imaging (fMRI) to determine the motor systems in the brain that are impaired in these children. They hope their findings will help them better understand the neural circuits involved in autism.
In particular, they hope that what they find out about the motor systems impaired in autism will point to parallel brain systems important for controlling social and communication skills. Initial findings show that, compared with normally developing children, children with autism have difficulty learning a motor sequence but are perfectly able to adapt a movement in response to a stimulus.
Several different theories about how various parts of the brain communicate with each other can explain this pattern of motor deficits. This grant will provide added funds to use anatomic MRI (aMRI), which will allow the researchers to examine more closely connections between the regions of the brain that may be involved.
What this means for people with autism:This research includes innovative approaches and techniques that will be used to investigate the theory that understanding abnormalities in motor learning in people with autism may provide important insight into social and communicative deficits, which are likely controlled by parallel systems in the brain. They will use brain imaging techniques to pin down the specific neural pathways affecting motor function in people with autism, and thereby gain insight into the more general neurological underpinnings of the disorder.
Stephen Porges, PhD
University of Illinois at Chicago
$50,000 for one year
Emotional Behavior – A Neurobiological Approach
A key feature of autism is the difficulty people with the disorder have in engaging socially with others. Over the past decade Dr. Porges has studied a neurobiological model of the social engagement system that he calls the polyvagal theory.
The theory is based on ideas about how the autonomic nervous system, which controls bodily functions such as breathing, heart rate, stress responses and emotional responses, evolved in humans and other mammals.
Dr. Porges argues that the nerves that regulate the body’s physiological state—heart rate, stress hormones, immune function—are linked to the nerves that regulate eye gaze, facial expression and listening.
These skills are a critical part of the social engagement system. For some people—people with autism, for example—their nervous system misreads the environment and turns on the defenses, making social interaction difficult or impossible.
This grant will provide bridge funding so the researchers can continue their research program of testing the polyvagal theory by recruiting participants for new studies that will use more refined measures of social engagement. The funding will also allow them to complete data collection, data analysis and publication of work that’s already under way.
What this means for people with autism: This research takes a unique perspective of social engagement behavior, providing a clear, testable theory of a neurological system that controls it. Results from this groundbreaking work may lead to the development of new laboratory-based measures of social engagement behavior that clinicians and researchers can use to assess individuals with autism.
Autistic people have fought the inclusion of ABA in therapy for us since before Autism Speaks, and other non-Autistic-led autism organizations, started lobbying legislation to get it covered by insurances and Medicaid.
ABA is a myth originally sold to parents that it would keep their Autistic child out of an institution. Today, parents are told that with early intervention therapy their child will either be less Autistic or no longer Autistic by elementary school, and can be mainstreamed in typical education classes. ABA is very expensive to pay out of pocket. Essentially, Autism Speaks has justified the big price tag up front will offset the overall burden on resources for an Autistic’s lifetime. The recommendation for this therapy is 40 hours a week for children and toddlers.
The original study that showed the success rate of ABA to be at 50% has never been replicated. In fact, the study of ABA by United States Department of Defense was denounced as a failure. Not just once, but multiple times. Simply stated: ABA doesn’t work. In study after repeated study: ABA (conversion therapy) doesn’t work.
What more recent studies do show: Autistics who experienced ABA therapy are at high risk to develop PTSD and other lifelong trauma-related conditions. Historically, the autism organizations promoting ABA as a cure or solution have silenced Autistic advocates’ opposition. ABA is also known as gay conversion therapy.
The ‘cure’ for Autistics not born yet is the prevention of birth.
The ‘cure’ is a choice to terminate a pregnancy based on ‘autism risk.’ The cure is abortion. This is the same ‘cure’ society has for Down Syndrome.
This is eugenics 2021. Instead of killing Autistics and disabled children in gas chambers or ‘mercy killings’ like in Aktion T4, it’ll happen at the doctor’s office, quietly, one Autistic baby at a time. Different approaches yes, but still eugenics and the extinction of an entire minority group of people.
Fact: You can’t cure Autistics from being Autistic.
Fact: You can’t recover an Autistic from being Autistic.
Fact: You can groom an Autistic to mask and hide their traits. Somewhat. … however, this comes at the expense of the Autistic child, promotes Autistic Burnout (this should not be confused with typical burnout, Autistic Burnout can kill Autistics), and places the Autistic child at high risk for PTSD and other lifelong trauma-related conditions.
[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]
Fact: Vaccines Do Not Cause Autism.