As the basic science of autism reveals increasing clues to the nature of this disorder, the broader research community is showing greater interest and ingenuity with respect to treatment options and translational research (applying laboratory findings and biomedical knowledge to clinical applications). With this growing interest as the backdrop, Cure Autism Now (CAN) held its annual treatment grant review meeting in Spring 2006.
The CAN Treatment Advisory Board reviewed and discussed 31 proposed autism treatment grants, up from only 11 grants submitted last year. "The most exciting part of the meeting was the progress in the overall level of the scientific studies proposed," commented Treatment Advisory Board member Evdokia Anagnostou, M.D., who treats individuals with autism at the Seaver Center for Autism at Mt. Sinai Medical School in New York City.
As a parent-driven organization, Cure Autism Now views the translation of research into programs and interventions that have the possibility of changing the course of our children's futures as a high priority. CAN supports a diverse body of scientific initiatives for the benefit of providing insights and practical outcomes to improve the lives and learning of individuals living with autism. These include:
- Treatment Grants, announced below
- A Clinical Trials Network, designed to standardize and speed up clinical trials, which is kicking off with a trial of memantine HCl (brand name Namenda)
- The Autism Treatment Network, which is laying the groundwork for collaborative clinical research in medical issues related to autism
- The Innovative Technology for Autism Initiative
Cure Autism Now is pleased to announce the following projects, selected from the submitted proposals on the basis of scientific merit and research design, as CAN's 2006 Treatment Grants.
While great effort usually goes into teaching spoken language to children with autism, relatively little effort is directed towards teaching the other form of language that is central to human communication, namely, written language. Agnes H. Whitaker, M.D., of Columbia University notes that this is particularly true for non-verbal children with autism, who are often assumed to be so impaired that any effort to teach language would be futile. Highlighting a few case reports of extensive written language abilities in some non-speaking individuals, Dr. Whitaker believes that teaching non-verbal children written language would provide them access to the invaluable skills of language and communication. This study will utilize A Light on Literacy, a program developed by Dr. Marion Blank, to develop a mode for expressive language and writing ability (both handwriting and keyboarding) in non-verbal children with autism. At the completion of the program, it is believed that the children will recognize and write words, as well as exhibit comprehension, answer questions and produce sentences about past, present and future events, resulting in a life-altering set of skills that have been considered beyond the reach of this population. This research also has significant potential to change the view of the language and cognitive abilities that are present, but challenging to access, in children on the autism spectrum.
Imitation is an early deficit noted in children with autism. Research has shown that the ability to spontaneously imitate is critical to learning new skills, including many related to language, joint attention and socialization, so addressing this domain may provide benefits beyond simple learning of imitation skills. In a three-year study, Brooke Ingersoll, Ph.D., of Lewis & Clark College will explore the effectiveness of using a naturalistic, play-based social-communication intervention she developed, termed Reciprocal Imitation Training (RIT). RIT targets generalized, spontaneous imitation skills within ongoing play in young children with autism. The assessments involved in this study are expected to offer further insight into the role of imitation in development of social-communicative skills, validate whether RIT is effective in improving this critical area of development, and determine which children are most likely to benefit, ultimately leading to more individualized treatment regimes.
In another evaluation of a specific model of educational treatment, a grant to Patricia K. Kuhl, Ph.D., and colleagues at the University of Washington will allow the use of behavioral and electrophysiological measures of speech processing to discern the effectiveness of an NIMH-funded Early Intervention project on language acquisition. Comparing the toddlers in the Early Intervention project (who receive intensive treatment focused on social interaction and language) with a control group receiving standard intervention services, the team will measure phonetic perception skills and social interest in speech, both of which have been shown to be important precursors to language acquisition in typically-developing children. In doing so, the investigators will examine the degree to which early language measures can serve as markers and predictors of the efficacy of treatments targeted at linguistic and social skill development in children with autism spectrum disorders.
As many caregivers of individuals with autism know, the high levels of anxiety that are often seen in this population can greatly inhibit learning and function, interfering with participation in activities and reducing opportunities for socialization. In a recent survey conducted by the National Autistic Society in England, anxiety was cited by parents as one of their biggest concerns. Yet, despite the significant impact of anxiety on the overall functioning of individuals with autism and related disorders, few intervention studies have been conducted and the treatment of anxiety in autism is primarily pharmacological. Research on treatment of anxiety in the general pediatric population has demonstrated that a specific intervention-cognitive-behavioral therapy-can be effective in reducing anxiety symptoms. The basic principles of cognitive-behavioral therapy include identification of the child's specific anxiety symptoms and situations that are viewed as anxiety-provoking, followed by gradual, supported exposures to manageable anxiety-producing situations that extend from hypothetical situations to real-life settings. Two of the new treatment studies will explore the use of cognitive-behavioral therapy in reducing the symptoms of anxiety in children with autism spectrum disorders.
At the University of Colorado, Denver, Judy A. Reaven, Ph.D. and Susan L. Hepburn, Ph.D. will build upon previous research in which they developed a standardized manual of family-focused cognitive-behavioral intervention. The current study will assess the effectiveness of this intervention, which is designed to reduce anxiety symptoms in children with high-functioning autism. Importantly, the investigators are developing the intervention in a group-based setting. Within the current constraints of managed care, such a group-based treatment would ultimately be more cost-effective and time-efficient, and the researchers have found that the group format promotes social support and the potential to alleviate isolation and stress often experienced by affected families.
Recognizing that autism-specific challenges present the need for modified anxiety treatment protocols, Jeffrey J. Wood, Ph.D. and Connie Kasari, Ph.D. at UCLA will evaluate the effects of addressing social skill deficits in conjunction with cognitive-behavioral therapy in a group of children with autism and anxiety. This project involves a clinical trial of a modified cognitive-behavioral therapy treatment manual developed by the investigators to target anxiety as well as social skills, such as friendship skills, peer-intervention and emotion education. Initial pilot cases have indicated reduced anxiety as well as gains in social functioning and self-help skills, and this study will evaluate the overall impact on children's functioning as well as the families' satisfaction with the intervention.
New research has shown that individuals with autism have biological impairments in activation of regions important for face recognition, perhaps explaining some of their noted social difficulties. Recent studies in control populations have found that training people on perceptual exercises can result in significant increases in brain activity in the very same regions noted to be functioning abnormally in autism, raising the hope of neural-retraining through practical exercises designed for individuals with autism. Catherine Lord, Ph.D., and colleagues from the University of Michigan will evaluate a set of computer games designed to increase attention to and processing of faces and facial expressions in children and adults with high-functioning autism. The games, designed by the Yale Child Study Center in conjunction with Dr. James Tanaka from the University of Victoria, focus on different face processing skills, such as recognizing different people's identities and reading their emotions, and interpreting gestures and gaze patterns. Most importantly, this study will examine whether a sustained and focused training curriculum improves not only face processing skills, but general social interaction skills as well. It also has the potential to provide a treatment approach for ameliorating social deficits in individuals with autism of any age. Moreover, if such computer-based instruction is successful, disseminating the treatment program would be easy and relatively inexpensive.
In addition to these treatment grants, at the meeting the Scientific Review Council approved a new bridge grant to Manya Angley, Ph.D. from the University of South Australia, who is searching for biomarkers relating to autism using modern analytical tools. With the aim of finding biological signatures of autism, the research group is using molecular profiling of urine to quantify metabolites. By linking the metabolic profiles with clinical data, Dr. Angley hopes to identify subtypes of autism and develop laboratory diagnostic tests that will make confirmed, earlier diagnoses possible.
In addition to these grants funded through the Treatment Grant mechanism, the CAN Scientific Review Council also noted several additional study proposals that contained promising objectives and areas of study. According to CAN's Science Director, Sophia Colamarino, Ph.D., "We are excited about several additional project ideas that were submitted for consideration, and are hopeful that we can work together with these researchers to expand the 2006 treatment program through targeted research opportunities."
We invite you to become involved in and support our Treatment Grant program or other Cure Autism Now research tinitiatives. Become a Friend of Treatment Grants with a gift of $5,000 or more or a Partner of Treatment Grants by co-sponsoring a specific grant with a gift of $25,000 or more. For more information on these and other opportunities and benefits please call Bret Prichard , Vice President for Development at (323) 549-0500. To read the full abstracts of the 2006 Treatment Grants see below.
Teaching Imitation Skills to Young Children with Autism: Predicting Response to a Naturalistic Social-Communication Intervention (Treatment Grant)
Brooke Ingersoll, Ph.D., Lewis & Clark College
Children with autism have deficits in imitation skills both in structured settings and in more natural contexts such as play with others. These deficits are a barrier to learning new skills as well as socialization, and are thus an important focus of early intervention programs for children with autism. Studies have found imitation ability to be strongly correlated with other social-communication behaviors in children with autism, suggesting that targeting imitation may assist development of other behaviors such as language and joint attention. This project is designed to validate Reciprocal Imitation Training (RIT), a naturalistic, play-based imitation intervention. In addition, we are exploring which child characteristics predict response to RIT and whether teachers find the intervention to be socially valid. Children in the experimental group will receive twelve weeks of the RIT intervention targeting imitation skills while children in the control group will receive their usual treatment from community providers. Changes in performance will be compared on a series of assessments of their imitation, language, play, and social skills administered pre- and post- treatment as well as at a three month follow-up. In sum, this research will examine the role of imitation in the development of other social-communicative skills in autism, offer insights as to how these early behaviors emerge in young children with autism as a result of treatment, and allow intervention providers to determine the best method for teaching imitation skills to young children with autism
Assessment of Treatment Outcome in Preschool Children with Autism Using Behavioral and Electrophysiological Measures of Speech Processing (Treatment Grant)
Patricia K. Kuhl, Ph.D., University of Washington
This project will use measures of speech processing to assess treatment success in children with autism enrolled in an ongoing NIMH-funded Early Intervention project. The Intervention program involves 18-30 month old toddlers with Autism Spectrum Disorder (ASD), half of whom are randomly assigned to an intensive early intervention treatment program that has a strong focus on social interaction and language. The control group receives standard intervention services through the community. We will examine how the Early Intervention program affects the linguistic skills of individual children with ASD, and their social interest in speech. Measurements include assessment of children's phonetic perception skills and their social interest in speech. Both components have been shown to be important precursors to language acquisition. Measures of early phonetic skill in typically developing infants predict the speed with which the child will progress towards language mastery. Social interest in speech is important because child-directed speech exaggerates the critical phonetic information in speech. In this project, evoked electrical brain potentials (ERP) of phonetic perception skills (syllable discrimination) and word processing skills, as well as a behavioral test of listening preference for child-directed speech, will be used as outcome measures in the treatment study. The design provides a powerful test of whether early and intensive intervention focused on language and social stimulation affects brain and behavioral measures of the linguistic and social processing of speech in children with autism.
Effects of a Face Perception Intervention on Social Skills in Individuals with Autistic Spectrum Disorders (Treatment Grant)
Catherine Lord, Ph.D., University of Michigan
Studies on the behavioral and social characteristics of Autistic Spectrum Disorders (ASD) have long identified deficits in face processing and recognition as an early feature of the disorder. Working with Dr. James Tanaka, a face processing researcher from the University of Victoria, the Yale Child Study Center has created an intervention designed to increase attention to and processing of faces and facial expressions using a set of computer games. This project is testing the efficacy of this computer game intervention on a sample of children and adults with high-functioning ASD. The computer games focus on different face processing skills, such as recognizing different people's identities and reading their emotions. The goals of this project are to assess the face processing skills of a sample of 60 people with high functioning ASD and to examine whether receiving this focused intervention has effects on not only face processing skills but also on broader social interaction skills. This research is integral to increasing knowledge and understanding of social deficits associated with ASD and whether they can be ameliorated. This information can lead to the development of effective interventions for ASD.
Group Cognitive Behavior Therapy for Children with Autism Spectrum Disorders and Anxiety Symptoms (Treatment Grant)
Judy A. Reaven, Ph.D. and Susan Hepburn, Ph.D., University of Colorado, Denver
Children with autism spectrum disorders are at greater risk for developing a variety of anxiety disorders than typically-developing children and those with other developmental disabilities. Anxiety symptoms interfere with participation in home, school, and community activities, narrowing opportunities for appropriate social engagement. Anxiety also significantly limits family activities, contributing to increased isolation for parents and siblings. Although many researchers and clinicians discuss the significant impact of anxiety on overall functioning of a person with autism, few intervention studies have been conducted. Research on treatment of anxiety in the general pediatric population has demonstrated that a specific intervention-cognitive-behavioral therapy-can be effective in reducing anxiety symptoms in children. The basic principles of cognitive-behavioral therapy include identification of the child's specific anxiety symptoms, as well as situations that are viewed as anxiety-provoking, and a very gradual exposure to manageable anxiety-producing situations. The present project builds upon previous research which has developed a standardized manual of family-focused cognitive-behavioral intervention. The primary purpose of the present study is to assess the effectiveness of this group-based family-focused intervention designed to reduce anxiety symptoms in children with high-functioning autism spectrum disorders
The Effectiveness of A Light on Literacy for Autism: A Case Control Study (Treatment Grant)
Agnes H. Whitaker, M.D., Columbia University
While great effort goes into teaching spoken language to children with autistic spectrum disorders (ASD), relatively little effort is directed towards teaching the other form of language that is central to human communication: namely, written language. This situation is particularly true of children in the ASD population who do not speak. Their limited speech has generally led to the view that these children are so impaired that any effort to teach written language would be futile. While few, there have been cases reported of extensive written language abilities in these individuals. If non-verbal children could be taught written language, they would then have access to the invaluable skills of language and communication that has otherwise been denied to them. The research that will be conducted will implement with non-speaking children a program entitled A Light on Literacy which has been developed by Dr. Marion Blank specifically for children with ASD. Through its use of specialized techniques that teach writing (both handwriting and keyboarding), the program provides the children with a mode for expressive language. At the completion of the program, it is expected that the children will have attained a set of skills that, in the past, have been considered beyond the reach of this population. This includes not simply word recognition and word creation, but in addition, comprehending and producing sentences connoting past, present and future, and answering questions about objects and events in the past, present and future.
Modified Cognitive Behavioral Therapy for Anxiety and Social Problems in Children with Autism (Treatment Grant)
Jeffrey J. Wood, Ph.D. and Connie Kasari, Ph.D. University of California, Los Angeles
Problems with anxiety are very common among children with ASD, and experts in the field have called for the development of treatments to address anxiety-related symptoms in this population. Anxiety can further complicate and impair the functioning of children who already face considerable challenges in development due to ASD. Recent clinical trials of cognitive behavioral therapy with neuro-typical children suggest that anxiety treatment for children with must go beyond skills training in hypothetical situations and also emphasize direct practice of new coping skills in the actual settings where problems are experienced. However, treatment protocols must be modified to accommodate ASD-specific challenges. Specifically, treatment must address social skill deficits in youth in order for optimal treatment response to occur. This project involves a clinical trial of a modified cognitive behavioral therapy treatment manual developed by the investigators to target anxiety and social skills. This includes friendship skills, peer intervention and emotion education in order to facilitate traditional cognitive behavioral treatment. Initial pilot cases have suggested this treatment can be quite effective with children with ASD, reducing their anxiety considerably with also significant gains in social functioning and self-help skills. This full study will now evaluate the overall impact on children's functioning as well as the families' satisfaction with the intervention.
Biomarkers and Diagnostics
Investigation of Etiology, Determination of Prognosis and Optimization of Interventions in Autism using Metabonomics (Biomarker Initiative Bridge Grant)
Manya T. Angley, Ph.D., University of South Australia
Autism is a lifelong condition that can have profoundly negative effects on an individual and their family with respect to social, economic and emotional well-being. Typically, the later the autism diagnosis, the greater the burden exerted on the education and health care systems. Early diagnosis followed by intensive and individualized intervention mitigates the negative impact of autism and can vastly enhance quality of life for the individual and their family. In this project, metabonomics (which is a cutting edge technology that examines patterns of metabolites in biofluids) will be used to identify features in urine that are distinctive for individuals with autism. If identified, these characteristic urine profiles may potentially be used as biomarkers to confirm an autism diagnosis and subtype different groups of autistic individuals, thereby offering indications for treatment opportunities.