Baylor College of Medicine, Houston , TX
2004

Principal Investigator: Arthur Beaudet, M.D.

Search for an Autism Gene on the Y Chromosome (funded through NAAR)

The male to female ratio in autism is 4:1 in the global autistic population. Despite this gender difference, male predisposition to autistic disorder has not been explained. The reduced rate at which people with autism have children makes vertical transmission uncommon and genetic analysis confusing. Furthermore, genome scans based on linkage analysis cannot study the non-recombining region of the Y chromosome and the lack of Y linkage in these studies does not rule out the possibility of susceptibility loci for autism on this chromosome. Dr. Beaudet proposes that a dysfunction of genes involved in synapse function and located on the Y chromosome can cause autism. To analyze for a Y chromosome effect in autism, Dr. Beaudet will screen Y chromosome haplotypes in subjects with autism and controls by using Y-polymorphic markers looking for specific haplogroups that could be associated with autism. Dr. Beaudet is also testing the hypothesis that the Y-linked SYBLI and NLGN4Y genes, whose products are molecules involved in the vesicular trafficking and synaptogenesis, are candidate genes for involvement in autism.

Arthur Beaudet

Boston University , Boston , MA
2004-2006

Principal Investigators: Helen Tager-Flusberg, Ph.D., Dae-Shik Kim, Ph.D.

Functional and Connectivity Neuroimaging of Autism.

The goal of this project is to develop over a three year period new methods that will allow exploration of brain regions that are critical for processing sounds and language. This project will utilize novel brain imaging technologies, including magnetic resonance imaging (MRI), to map out areas of the brain in control subjects that process sounds and language. This will allow us to locate brain areas in which certain processes take place and to determine how these areas are connected to one another. The project will use these technologies and knowledge on adolescents with autism to shed light on regions of the brain which may not be processing sounds or language efficiently and where connections between critical brain regions may break down in autism.

Helen Tager-Flusberg

Dae-Shik Kim

Boston University School of Medicine, Boston , MA
2004

Principal Investigator: Robert Joseph, Ph.D.

Neurobiological Markers of Language and Functioning in Autism (funded through NAAR)

This project will investigate the relationship of language acquisition to developments in connectivity between language regions of the brain, as measured by diffusion tensor magnetic resonance imaging in children with autism. Many children with autism fail to develop language or are impaired in their language functioning. Research has shown that language impairment appears to represent the influence of genes that increase susceptibility to autism. An understanding of neurobiological bases of the language deficits in autism will contribute to an understanding of autism's genetic underpinnings and neurodevelopmental etiology. Evidence of white matter brain abnormalities, particularly of cerebral white matter overgrowth, has emerged from magnetic resonance imaging (MRI) studies of children with autism. These findings have been limited to macrostructural estimates of differences in white matter volume in autism. Dr. Joseph will use diffusion tensor imaging (DTI) technology to (a) examine the microstructural integrity and coherence of white matter tracts connecting language-related regions of the cerebral cortex and (b) to evaluate relationship of white matter connectivity to actual language functioning. Dr. Joseph will collect anatomical and diffusion tensor brain images from children with autism at age 3 and one year later, and examine the relationship between white matter connectivity in language regions of the brain to measures of children's language development taken at each time. Dr. Joseph will assess whether microstructural changes in language-related white matter predict acquisition and development of language skills in children with autism.

Boston University School of Medicine

Robert Joseph

Brandeis University
Symposium on Autism and Behavioral Genomics
Waltham , MA
2004

Brandeis University

Children's Hospital - Boston , Boston , MA
2004-2008

Principal Investigators: Michael E. Greenberg, Ph.D., Isaac Kohane, M.D, Ph.D., Louis M. Kunkel, Ph.D .

Genetic Studies of Autism Spectrum Disorders

This study will utilize genetics, bioinformatics, and neuroscience programs at Children's Hospital-Boston to address the genetic basis of autism spectrum disorders (ASD). One hypothesis of this study is that there are genetic variants that may predispose an individual to develop ASD, and that these genes can be identified by transmission disequilibrium testing (TDT) of candidate genes in pathways logically indicated based on gene expression and neuronal activity studies. Using TDT and trios (child with autism and their parents), and affected sib pairs (ASP) analysis, studies will be performed to look for association of ASD with candidate genes and for linkage peaks associated with ASD. Another hypothesis of this study is that there are differences in gene expression in the white blood cells of children with autism in comparison with normal children. Microarray analysis will be performed to study differences in gene expression in white blood cells of children with autism compared with that of normal children. Sparked by evidence that autism may be caused by defective synaptic maturation and the finding that activity-dependent gene transcription plays a role in synapse maturation, a third hypothesis of this study is that mutations of transcriptional regulators and their target genes may underlie some forms of autism.

Greenberg Laboratory

Kohane Laboratory

Kunkel Laboratory

Friends of Freie Universität Berlin in New York- Der Freie Universität Berlin
Organizational Meeting for Dahlem Workshop to be entitled, "Re-conceptualizing Autism: Identifying the Neural Mechanisms Underlying Autistic Behaviors"
2004

The NLM Family Foundation supported a preliminary, organizational meeting held in Chicago in preparation for a Dahlem Workshop entitled, "Re-conceptualizing Autism: Identifying the Neural Mechanisms Underlying Autistic Behaviors". The Dahlem Workshop on autism research brought together scientists from a broad range of disciplines to develop a new developmental focused research agenda for autism that would refine the behavioral phenotype of autism and identify neural, genetic, epigenetic, and environmental mechanisms that mediate autistic behaviors. Themes for working groups were The Autistic Nervous System and Personal Adaptation; Systems Neurobiology through the Life Span; Gene Discovery, Gene Regulation, and Neurogenetic Models; and Environmental Mediators: Risk and Protective Factors.

Friends of Freie Universität Berlin in New York

International Association for Disability and Oral Health
Addressing Dental Care for Individuals with Autistic Disorders (Pre-Conference Symposium)
Calgary , Alberta
2004

Held at the University of Calgary , the symposium was a full-day pre-conference event at the XVII International Congress on Disability and Oral Health hosted by the International Association for Disability and Oral Health. This pre-conference symposium focused on providing dental care to those with autistic disorders. Presentation topics included Advocating for Access to Dental Care, Identifying Behavior and Management Strategies, Oral Findings in Children with Autistic Disorders, and Adverse Oro-Facial Reactions to Medications Used to Treat Autism. With funding from the NLM Family Foundation, Dr. Tesini led a pre-conference symposium focused on providing dental care to individuals with autism.

International Association for Disability and Oral Health

Kennedy Krieger Institute/ Johns Hopkins School of Medicine, Baltimore , M.D.
2004

Principal Investigator: Stewart Mostofsky, Ph.D.

Dependent Motor Learning in Autism Examination of Visual and Somatosensory (funded through NAAR)

Increased insight into the brain mechanisms underlying autism can be gained from consideration of motor abnormalities of individuals with autism. By using tests of motor function for which the neurologic basis is well mapped out, it is possible to gain an understanding of the neural circuits impaired in autism. Motor signs can serve as markers for deficits in parallel brain systems important for control of social and communication skill impairments observed in autism. Among the most consistently observed motor abnormalities in autism is difficulty with imitation and performance of skilled motor tasks and gestures. These deficits could be secondary to a fundamental problem with acquiring motor skills. Deficiencies in motor skill learning could also result in development of a limited repertoire of movements and might explain observations of motor stereotypies. The goals of this project are to determine common factors underlying motor deficits in autism and to investigate brain abnormalities associated with these deficits using functional magnetic resonance imaging. A long-term goal is to examine the association of impaired motor skill learning with socialization and communication deficits that characterize autism. This study will provide insight into the neurologic basis of motor deficits in autism and may provide a basis for understanding the neurologic underpinnings of impaired social/communicative development.

Kennedy Krieger Institute

Stewart Mostofsky

Massachusetts Advocates for Children, Boston, MA
2002, 2003, 2004, 2005

Establishment and Support of the Autism Special Education Legal Support Center

The goal of this project is to provide training, technical assistance, and advocacy services necessary to ensure that children with autism receive equal educational opportunities. Goals include: Providing parents with information about state-of-the-art services and programs available to meet individual needs of students with disabilities; Insuring that children with autism receive special education services necessary to reach their potential in areas impacted by their disability; Increasing public awareness and understanding of the potential and competency of individuals with autism, targeting policy makers, media, educators, service providers, as well as the general public. The Autism Special Education Legal Support Center will accomplish these goals by: providing community-based workshops for parents, educators, and medical professionals regarding legal rights and range of service options available for children with autism; providing a hotline to give legal and technical assistance to families of children with autism; training attorneys to increase representation of low-income students with autism to ensure that children receive legally mandated special education services; and providing information to the media, the legislature, and other policy makers regarding changes necessary to ensure children with autism receive services that reflect their potential.

Massachusetts Advocates for Children

Massachusetts Institute of Technology, Cambridge , MA
2004-2006

Principal Investigator: Damon Page, Ph.D.

Toward an Understanding of the Developmental Basis of Brain Dysfunction in Autism: Molecular and Cellular Mechanisms of Cortical Region and Network Formation

The cerebral cortex is made up of anatomically and functionally distinct regions and past evidence has suggested that abnormal formation and activity of certain areas may be involved in autism. This research will investigate morphological and functional regionalization of the mammalian cerebral cortex in normally developing mouse models to understand how the development of the cerebral cortex may be disrupted in autism. The use of diverse tools available in mice will enable us to understand how genes cooperate with one another and with extrinsic signals to build regions and functional circuitry in the cerebral cortex. This research will provide a basis for understanding how processes may be disrupted in individuals with autism, and should contribute to better diagnosis and treatment of this condition.

Laboratory of Mriganka Sur

Museum of Fine Arts , Boston, MA
2003, 2004

Pilot Program for Adults with Cognitive Disabilities and Autism

The NLM Family Foundation supports workshops at the Museum of Fine Arts designed for people with cognitive, learning, and/or developmental disabilities, those with autism spectrum disorders, and their friends and families. One workshop is intended for young people to age 12, and the other is for adolescents and adults. The participants explore the art in the Museum of Fine Arts ' collections and exhibitions through sound, theater exercises, music, movement, and visual art.

Museum of Fine Arts

North Shore Long Island Jewish Research Institute, Manhasset , New York
2004-2006

Principal Investigator: Peter K. Gregersen, M.D.

Autism and Absolute Pitch

This project is based on the hypothesis that there are common genetic factors involved in autism and a rare cognitive ability in normal subjects known as absolute pitch (also called "perfect pitch"). This research will utilize an internet-based test which can detect absolute pitch ability without the need to know conventional musical designations for pitch. Using this test, individuals with autism and their family members will be formally tested for absolute pitch ability. Researchers will investigate whether genes that may carry predisposition to absolute pitch are also involved in genetic predisposition to autism. This project may provide insight into the genetics of autism by studying a readily measurable trait (absolute pitch) to identify candidate genes.

North Shore Long Island Jewish Health System

Personal Advocacy and Lifetime Support (PALS), North Waltham, MA
2002, 2004

Operating Support and Support for the Printing of PALS, Inc. Volunteer Packet

The NLM Family Foundation provides support to PALS, a non-profit organization whose mission is to help parents and other caregivers establish and maintain a lifetime plan for a safe and secure future for their loved one with special needs. Many families with an individual with special needs often express concern over what will happen to their loved when they are gone. PALS believes that the best guarantee of a safe and secure future for individuals with special needs is a circle of caring, committed friends, family members, supporters, and professionals actively involved in their lives. The cornerstone of PALS is a Personal Support Network, which consists of people who make a long term commitment to be in a voluntary relationship with individuals with special needs.

Personal Advocacy and Lifetime Support (PALS)

University College London , Behavioral and Brain Sciences Unit / Institute of Child Health, London , UK
2004-2006

Principal Investigator: David H. Skuse, M.D.

A Family Study of Genetic Susceptibility to Autistic Traits

Research has shown that not everyone who has the genetic susceptibility to autism will become autistic. It is believed that gene discovery in autism could be facilitated by use of endophenotypes in linkage and association studies. Endophenotypes are hidden indicators of genetic susceptibility reflecting underlying disruption to covert processes such as cognition, and they are not directly correlated with behavioral expression of risk. The goal of this research is to test the hypothesis that genetic susceptibility to a social-cognitive endophenotype in children with autism and their first degree relatives is due to allelic variance in the same risk haplotypes that are of relevance to Turner syndrome. The long term goal is to discover specific genes that influence development of social cognition in males and females and which increase susceptibility to autism in families with a child with autism.

Institute of Child Health

University of Cambridge Autism Research Centre, Cambridge , UK
2004-2007

Principal Investigator: Simon Baron-Cohen , Ph.D.

A Genetic Study of Mathematical Talent and Asperger's Syndrome

Autism spectrum disorders often involve impaired empathy and intact or talent in systemizing. Research has suggested a link between talent in systemizing and the likelihood of autism in a family. This suggests that one of the genes involved in autism may be the gene (or genes) that underlie systemizing talent. This research attempts to identify genes associated with a well-defined example of systemizing talent, mathematical giftedness. Researchers will obtain DNA from large families where there are many gifted mathematicians, and will re-test any significant regions of the DNA in detail in a sample of mathematicians vs. non-mathematicians. Researchers are also studying DNA of people with Asperger Syndrome (AS) to see if the genes for systemizing are implicated in the genes for AS. Genetic research may improve early diagnosis of autism spectrum conditions.

Autism Research Centre

Simon Baron-Cohen

University of Cambridge Autism Research Centre, Cambridge , UK
2004-2007

Principal Investigator: Simon Baron-Cohen, Ph.D.

Do Children with Autism Have Elevated Fetal Testosterone?

Neurologist, Norman Geschwind, suggested that fetal testosterone may shape sex differences in brain development. Males produce more of this because it is generated by the testes, but females also produce it. Geschwind thought that the action of fetal testosterone on the brain might explain why girls tend to talk earlier than boys and why boys are overrepresented in clinics for language disorders and conditions such as autism. Human fetal testosterone can be measured through a method called amniocentesis. In this study, amniotic fluid taken from 3,000 women during their pregnancies will be studied with respect to levels of fetal testosterone. Dr. Baron-Cohen will determine how many of their children, who are now 4 years or older, have been diagnosed with an autism spectrum condition, or score highly on an autism spectrum scale, and will test if these 'affected' children had abnormally high levels of fetal testosterone.  Earlier studies in the general population have linked this hormone to social and language development. It is important to investigate whether it plays a role in the development of autism.

Autism Research Centre

Simon Baron-Cohen

University of Cambridge Autism Research Centre, Cambridge , UK
2004-2005

Principal Investigator: Emma Weisblatt, Ph.D.

DNA Collection from a Cohort of Children with Asperger's Syndrome, PDD-NOS and High-Functioning Autism and their Families

This project involves the collection of DNA samples from 100 to 150 probands of high-functioning patients with autism spectrum diagnoses and their parents and siblings. Researchers will use a candidate gene approach to contribute to the search for autism susceptibility genes. One of the major aims of this research is to investigate phenotypic markers, such as sensory processing differences or electrophysiological differences, for use in genetic studies. These will help to identify subgroups of patients with autism who may differ in their underlying neurobiological characteristics.

Autism Research Centre

Emma Weisblatt