The first results from a scan of the world's largest collection of DNA samples from families affected by autism point to two new genetic links that may predispose people to the brain disorder. Nature Genetics reports the study's findings in its Feb. 18 online edition.
The five-year study was led by the Autism Genome Project, an international consortium involving scientists from 50 institutions in 19 countries. Founded in 2002 with funding from the nonprofit Autism Speaks and the National Institutes of Health, the group shared DNA samples, data and expertise in a coordinated effort to identify autism-susceptibility genes.
"This degree of collaboration is an unprecedented effort in autism research and demonstrates that a genetic approach is a powerful way to deepen understanding of the disease," said Dr. Daniel Geschwind, director of the Neurogenetics Program at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, one of the study's 13 research centers.
"This large-scale study reveals that autism is an extremely diverse condition," Geschwind noted. "Our findings suggest that autism has numerous genetic origins, rather than a single or few major causes."
The consortium used gene-chip technology to search for genetic commonality in autistic individuals from nearly 1,200 families. The scientists also scanned DNA from these families for variations in gene copy numbers -- tiny genomic insertions and deletions that scientists believe might be involved with autism.
"The large number of families in this study permitted us to organize autistic children with similar features of this disorder into smaller groups, where gene linkages may be more easily detected," observed Rita Cantor, professor of human genetics at the David Geffen School of Medicine at UCLA.
Results of the two-pronged approach implicated a previously unidentified region of chromosome 11; and neurexin 1, a member of a gene family believed to play a key role in communication between brain cells. The neurexin finding highlighted a group of brain cells called glutamate neurons and the genes affecting their development and function, suggesting that they play a critical role in autism spectrum disorders.
"We are excited by the results from this large-scale study," said Dr. Stanley Nelson, professor of human genetics at the David Geffen School of Medicine at UCLA, "At the same time, we must greatly increase the number of autistic persons in our genetic analysis in order to fully describe heredity's role in the disease."
"We hope that identifying these genes will provide new insights into what underlies autism," added Geschwind. "We are optimistic that this approach will lead to improved interventions for autistic children and better quality of life for their families."
In 1997, the citizens' group Cure Autism Now (CAN) created a gene bank in order to advance genetic research on autism. UCLA partnered with CAN to add more than 400 families to the gene bank, called the Autism Genetic Resource Exchange, which contributed one-third of the clinical data and samples analyzed by the Autism Genome Project in this study.
The UCLA families who participated had more than one member diagnosed with one of three genetically related diseases: autism, pervasive developmental disorder or Asperger's syndrome. Earlier this month, CAN merged with Autism Speaks to pool their efforts to fund and advance autism research. Autism is a complex brain disorder that strikes in early childhood, often as young as 2 or 3. The condition disrupts a child's ability to communicate and develop social relationships, and is often accompanied by acute behavioral challenges. While the cause remains unknown, scientists suspect the disease is highly hereditary.
Naming autism as a national public health crisis, the Centers for Disease Control and Prevention report that one in 150 American children is diagnosed with an autism spectrum disorder. Affecting four times as many boys as girls, the diagnosis of autism has expanded tenfold in the last decade.
The UCLA Center for Autism Research and Treatment provides diagnosis, family counseling and treatment for patients with autism. Its research focuses on understanding the origins of the disorder's social, communicative and language deficits, and designing and testing new treatments to help autistic children and adults. The center also centralizes autism resources at UCLA and builds partnerships within the autism community.
UCLA is one of eight centers in the NIH-funded Studies to Advance Autism Research and Treatment network, and one of 10 original Collaborative Programs for Excellence in Autism. For more information, see http://www.autism.ucla.edu.
University of California, Los Angeles (UCLA), Health Sciences
924 Westwood Blvd., Ste. 350
Los Angeles, CA 90095
United States
http://healthcare.ucla.edu/
May 7, 2007
Largest Genomic Search Finds Genes That May Contribute To Autism
An international team of researchers from 19 countries has identified one gene and a previously unidentified region of another chromosome as the location of another gene that may contribute to a child's chances of having autism.
The findings, based on genetic samples from nearly 1,200 families with two or more children who have autism, were published today in Nature Genetics by more than 120 scientists from Europe and North America who make up the Autism Genome Project.
The project was launched in 2002 by scientists at 50 institutions to share data, samples and expertise in an effort to speed up the process of identifying susceptibility genes, those that heighten a child's risk of having the developmental disorder. Seven University of Washington researchers are coauthors of the paper including lead project investigators Gerard Schellenberg and Geraldine Dawson.
The research was funded by Autism Speaks, a nonprofit organization dedicated to increasing awareness of autism and raising money to fund autism research, and the National Institutes of Health.
The consortium scientists utilized statistical power from the largest set of autism-related genetic material yet examined. The researchers found neurexin 1, part of a family of genes that plays a role with the neurotransmitter glutamate, and a still-to-be-pinpointed gene on chromosome 11 to be likely susceptibility genes for autism.
"Neurexin 1 is a highly likely candidate," said Schellenberg, a researcher at the Puget Sound Veterans Affairs Medical Center and a research professor of medicine at the UW. "It is a protein that enables one neuron to contact another neuron. Often you don't have any idea of what a gene does, but in this case we know neurexin 1 is involved at sites where the neurotransmitter glutamate is released. Glutamate is a brain chemical that has been previously implicated in autism. The new finding suggests that the gene is potentially important in autism.
"As for the chromosome 11 location, we think there is another susceptibility gene there and we are actively pursuing it. We are in the neighborhood and have a plan to find it."
Dawson, who directs the UW's Autism Center and is a professor of psychology, said the identification of neurexin 1 is important because glutamate is known to be involved in learning. By identifying this gene it begins to allow researchers "to go from gene to brain to behavior in a way we haven't gone before," she said. "This is a pretty big step and is a precedent showing that autism will require this kind of collaboration to make progress. It is doubtful that any single laboratory could have come up with this kind of finding. This is just the beginning of the fruits from this collaboration."
The Autism Genome Project used two techniques to examine the DNA of the nearly 1,200 families with a history of autism. Researchers used so-called "gene chip" technologies to look for genetic similarities among these family members. In addition, the team scanned the same DNA for what are called copy number variations. These are submicroscopic insertions and deletions of genetic material that scientists believe may be involved with autism and other common diseases.
Schellenberg said copy number variations are fairly common in the human genome and many of them are believed to be benign. "But until you know the function, you don't know what happens when there is an insertion or deletion of this genetic material," he added.
Scientists believe that there may be five or six major genes and perhaps as many as 30 other genes involved in autism. Inheriting more of these genes or certain ones is thought to increase a child's likelihood of being born with autism or a more severe form of the disorder, just as there are genes that heighten a person's chances for inheriting breast cancer or heart disease.
Autism is actually a spectrum of disorders that inhibits a person's ability to communicate and develop social relationships. It is often accompanied by extreme behavior challenges. Autism Spectrum Disorders are diagnosed in one of 166 children in the United States and affect four times as many boys as girls.
"These findings are a piece of the puzzle. As we identify these genes we will be able to screen young children for autism at an early age and begin interventions earlier, which can have a dramatic effect for some children," Dawson said.
A second phase of the Autism Genome Project also was announced today to continue the effort to discover the genes that cause the disorder. This $14.5 million phase is being funded by Autism Speaks, the British Medical Research Council, the Health Research Board of Ireland, Genome Canada and its partners, Canadian Institutes for Health Research, Southwest Autism Research and Resource Center, and the Hilibrand Foundation.
Other UW researchers who contributed to the research are Annette Estes, Jeff Munson, Elena Korvatska, Ellen Wijsman and Chang-En Yu.
University of Washington
Box 351207 Gerberding Hall
Seattle, WA 98195
United States
http://www.washington.edu/
The findings, based on genetic samples from nearly 1,200 families with two or more children who have autism, were published today in Nature Genetics by more than 120 scientists from Europe and North America who make up the Autism Genome Project.
The project was launched in 2002 by scientists at 50 institutions to share data, samples and expertise in an effort to speed up the process of identifying susceptibility genes, those that heighten a child's risk of having the developmental disorder. Seven University of Washington researchers are coauthors of the paper including lead project investigators Gerard Schellenberg and Geraldine Dawson.
The research was funded by Autism Speaks, a nonprofit organization dedicated to increasing awareness of autism and raising money to fund autism research, and the National Institutes of Health.
The consortium scientists utilized statistical power from the largest set of autism-related genetic material yet examined. The researchers found neurexin 1, part of a family of genes that plays a role with the neurotransmitter glutamate, and a still-to-be-pinpointed gene on chromosome 11 to be likely susceptibility genes for autism.
"Neurexin 1 is a highly likely candidate," said Schellenberg, a researcher at the Puget Sound Veterans Affairs Medical Center and a research professor of medicine at the UW. "It is a protein that enables one neuron to contact another neuron. Often you don't have any idea of what a gene does, but in this case we know neurexin 1 is involved at sites where the neurotransmitter glutamate is released. Glutamate is a brain chemical that has been previously implicated in autism. The new finding suggests that the gene is potentially important in autism.
"As for the chromosome 11 location, we think there is another susceptibility gene there and we are actively pursuing it. We are in the neighborhood and have a plan to find it."
Dawson, who directs the UW's Autism Center and is a professor of psychology, said the identification of neurexin 1 is important because glutamate is known to be involved in learning. By identifying this gene it begins to allow researchers "to go from gene to brain to behavior in a way we haven't gone before," she said. "This is a pretty big step and is a precedent showing that autism will require this kind of collaboration to make progress. It is doubtful that any single laboratory could have come up with this kind of finding. This is just the beginning of the fruits from this collaboration."
The Autism Genome Project used two techniques to examine the DNA of the nearly 1,200 families with a history of autism. Researchers used so-called "gene chip" technologies to look for genetic similarities among these family members. In addition, the team scanned the same DNA for what are called copy number variations. These are submicroscopic insertions and deletions of genetic material that scientists believe may be involved with autism and other common diseases.
Schellenberg said copy number variations are fairly common in the human genome and many of them are believed to be benign. "But until you know the function, you don't know what happens when there is an insertion or deletion of this genetic material," he added.
Scientists believe that there may be five or six major genes and perhaps as many as 30 other genes involved in autism. Inheriting more of these genes or certain ones is thought to increase a child's likelihood of being born with autism or a more severe form of the disorder, just as there are genes that heighten a person's chances for inheriting breast cancer or heart disease.
Autism is actually a spectrum of disorders that inhibits a person's ability to communicate and develop social relationships. It is often accompanied by extreme behavior challenges. Autism Spectrum Disorders are diagnosed in one of 166 children in the United States and affect four times as many boys as girls.
"These findings are a piece of the puzzle. As we identify these genes we will be able to screen young children for autism at an early age and begin interventions earlier, which can have a dramatic effect for some children," Dawson said.
A second phase of the Autism Genome Project also was announced today to continue the effort to discover the genes that cause the disorder. This $14.5 million phase is being funded by Autism Speaks, the British Medical Research Council, the Health Research Board of Ireland, Genome Canada and its partners, Canadian Institutes for Health Research, Southwest Autism Research and Resource Center, and the Hilibrand Foundation.
Other UW researchers who contributed to the research are Annette Estes, Jeff Munson, Elena Korvatska, Ellen Wijsman and Chang-En Yu.
University of Washington
Box 351207 Gerberding Hall
Seattle, WA 98195
United States
http://www.washington.edu/
Autism Expert Creates Innovative Intervention Program
Autism is the fastest growing disability in the United States, and public school systems are trying to catch up. One out of every 166 children is diagnosed with autism, making it more common than pediatric cancer, diabetes and AIDS combined.
The Autism Support Services: Education, Research, and Training (ASSERT) program at Utah State University is a state-of-the-art preschool program that uses research-based techniques to address the individual needs of autistic children. USU's pioneer site has opened the doors to a new world for children with autism and is a model training classroom for professionals in the Intermountain region.
Early intervention is key to helping children with autism, and the ASSERT program at Utah State serves as the training grounds for the educators who will make a difference in classrooms. The program offers children a chance to receive help at a young age.
Thomas Higbee, director of USU's Autism Support Services, spent more than 10 years researching and developing cutting-edge ideas that sparked the birth of the ASSERT program. Research has shown that children with autism spectrum disorders (ASD) do not learn readily in typical environments, so Higbee fashioned an atmosphere ideally constructed for ASD treatment.
ASSERT provides consultation services and curriculum to school districts. Higbee and his graduate students frequently visit sites in school districts to provide in-depth training and ensure that students are getting the best instruction possible.
"The hard work has really paid off and we have seen dramatic positive changes in our students," said Higbee.
This individualized educational program has been improving the lives of children with ASD since 2003. What started as a 10-week summer course has become a highly-successful year-round preschool program that continues to revolutionize the way children with autism are educated.
This innovative program serves children three to five years in age. Each child has a personal instructor to work with for 20 hours a week and is given an individualized plan tailored to their needs.
"Intensive behavioral intervention for young children with autism is important because the earlier you work with the children, the bigger positive impact you can have on their progression," Higbee said.
The preschool program also teaches social skills and encourages leisure and play activities with structured peer-play interactions. Functional behavioral assessment and intervention techniques are used to address challenging behaviors.
"Learning doesn't stop at the classroom threshold," Higbee said.
Family training and participation is critical to the success of the program. Families receive periodical professional training and home visits by a team leader twice per month to learn how to continue the program at home.
Fawn Rigby's four-year-old son Zac is a student in the ASSERT program. This education has affected young Zac's life dramatically, and his mother is enthusiastic about ASSERT.
"It's amazing," Rigby said. "ASSERT has given Zac the personal attention he needed. After just a few months, the progress I've seen in him is remarkable."
Higbee has been very satisfied with the outcome of the program and the positive change in the students.
"The life-changing improvements we have expected from our students are happening," Higbee said.
The impact on the students and significant changes can be credited to the intense training and professional caliber of the instructors. Graduate and undergraduate students at USU can apply to work in the program and earn either university credit or compensation while learning how to effectively teach students with ASD.
Higbee said the ASSERT success comes from the rigorous training and satellite program. USU's ASSERT classroom serves as a training site for current and future special education teachers and professionals in related areas such as psychology and speech pathology.
"A big part of our students' success is due to our collaboration with ASSERT," said an aid at a local preschool. "The staff training and continual on-site visits have been vital in keeping our staff qualified to serve our students."
Through ASSERT training, professionals are able to learn behavioral intervention techniques and demonstrate knowledge of behavior principles and how to apply them.
"I have seen a tremendous amount of growth in each child, and I attribute it to the intensive individual programs that are implemented daily," a teacher at a local school said.
ASSERT also provides training to school district personnel on effective educational and behavioral strategies for students with autism. ASSERT continues to help students after preschool and throughout their experience in the public education system.
Dr. Thomas S. Higbee is a national expert on both assessment and intervention strategies for people with autism. He has published 15 research studies and given more than 50 presentations at state and national conferences on the topic. He is Director of the program Autism Support Services: Education, Research, and Training (ASSERT), which he founded in 2003. Over the past 10 years, he has worked with children with developmental disabilities in home-, center-, and school-based programs. He has trained teachers in school districts in California, Utah, Idaho and Wyoming. Dr. Higbee is an assistant professor in the Department of Special Education and Rehabilitation at Utah State University where he has worked since 2002. Before coming to USU, Dr. Higbee served for three years as Senior Clinician at Spectrum Center for Educational and Behavioral Development in Berkeley, Calif., a non-profit agency that operates non-public schools for students with severe disabilities and behavioral disorders.
Utah State University
0500 Old Main Hill
Logan, UT 84322-0500
United States
http://www.usu.edu/ust
The Autism Support Services: Education, Research, and Training (ASSERT) program at Utah State University is a state-of-the-art preschool program that uses research-based techniques to address the individual needs of autistic children. USU's pioneer site has opened the doors to a new world for children with autism and is a model training classroom for professionals in the Intermountain region.
Early intervention is key to helping children with autism, and the ASSERT program at Utah State serves as the training grounds for the educators who will make a difference in classrooms. The program offers children a chance to receive help at a young age.
Thomas Higbee, director of USU's Autism Support Services, spent more than 10 years researching and developing cutting-edge ideas that sparked the birth of the ASSERT program. Research has shown that children with autism spectrum disorders (ASD) do not learn readily in typical environments, so Higbee fashioned an atmosphere ideally constructed for ASD treatment.
ASSERT provides consultation services and curriculum to school districts. Higbee and his graduate students frequently visit sites in school districts to provide in-depth training and ensure that students are getting the best instruction possible.
"The hard work has really paid off and we have seen dramatic positive changes in our students," said Higbee.
This individualized educational program has been improving the lives of children with ASD since 2003. What started as a 10-week summer course has become a highly-successful year-round preschool program that continues to revolutionize the way children with autism are educated.
This innovative program serves children three to five years in age. Each child has a personal instructor to work with for 20 hours a week and is given an individualized plan tailored to their needs.
"Intensive behavioral intervention for young children with autism is important because the earlier you work with the children, the bigger positive impact you can have on their progression," Higbee said.
The preschool program also teaches social skills and encourages leisure and play activities with structured peer-play interactions. Functional behavioral assessment and intervention techniques are used to address challenging behaviors.
"Learning doesn't stop at the classroom threshold," Higbee said.
Family training and participation is critical to the success of the program. Families receive periodical professional training and home visits by a team leader twice per month to learn how to continue the program at home.
Fawn Rigby's four-year-old son Zac is a student in the ASSERT program. This education has affected young Zac's life dramatically, and his mother is enthusiastic about ASSERT.
"It's amazing," Rigby said. "ASSERT has given Zac the personal attention he needed. After just a few months, the progress I've seen in him is remarkable."
Higbee has been very satisfied with the outcome of the program and the positive change in the students.
"The life-changing improvements we have expected from our students are happening," Higbee said.
The impact on the students and significant changes can be credited to the intense training and professional caliber of the instructors. Graduate and undergraduate students at USU can apply to work in the program and earn either university credit or compensation while learning how to effectively teach students with ASD.
Higbee said the ASSERT success comes from the rigorous training and satellite program. USU's ASSERT classroom serves as a training site for current and future special education teachers and professionals in related areas such as psychology and speech pathology.
"A big part of our students' success is due to our collaboration with ASSERT," said an aid at a local preschool. "The staff training and continual on-site visits have been vital in keeping our staff qualified to serve our students."
Through ASSERT training, professionals are able to learn behavioral intervention techniques and demonstrate knowledge of behavior principles and how to apply them.
"I have seen a tremendous amount of growth in each child, and I attribute it to the intensive individual programs that are implemented daily," a teacher at a local school said.
ASSERT also provides training to school district personnel on effective educational and behavioral strategies for students with autism. ASSERT continues to help students after preschool and throughout their experience in the public education system.
Dr. Thomas S. Higbee is a national expert on both assessment and intervention strategies for people with autism. He has published 15 research studies and given more than 50 presentations at state and national conferences on the topic. He is Director of the program Autism Support Services: Education, Research, and Training (ASSERT), which he founded in 2003. Over the past 10 years, he has worked with children with developmental disabilities in home-, center-, and school-based programs. He has trained teachers in school districts in California, Utah, Idaho and Wyoming. Dr. Higbee is an assistant professor in the Department of Special Education and Rehabilitation at Utah State University where he has worked since 2002. Before coming to USU, Dr. Higbee served for three years as Senior Clinician at Spectrum Center for Educational and Behavioral Development in Berkeley, Calif., a non-profit agency that operates non-public schools for students with severe disabilities and behavioral disorders.
Utah State University
0500 Old Main Hill
Logan, UT 84322-0500
United States
http://www.usu.edu/ust
Characteristics Of Patients At Increased Risk For Compulsive Gambling Associated With Taking Parkinson's Meds
Patients with Parkinson's disease who are younger when they develop the condition, have a personality trait known as novelty-seeking or whose personal or family history includes alcohol abuse may be more likely to develop pathological gambling as a side effect of medications used to treat their condition, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals.
Behaviors associated with impulse control Including compulsive shopping, hypersexuality, binge eating and pathological gambling have been associated with dopamine agonists, medications used to treat Parkinson's disease. In studies examining the relationship between dopamine agonists and compulsive gambling, the likelihood of gambling problems was unrelated to the medication dosage. This suggests that an underlying trait may interact with the drugs and make an individual more vulnerable to this adverse effect.
Valerie Voon, M.D., National Institute of Neurological Disorders and Stroke, Bethesda, Md., and colleagues compared the characteristics of 21 patients with Parkinson's disease who developed pathological gambling habits after beginning to take dopamine agonists with 42 patients with Parkinson's disease who did not develop compulsive behaviors. The participants, who all visited a clinic in Toronto, Canada, between June 2003 and October 2005, were examined by neurologists and completed assessment scales that measured their levels of impulsivity, substance abuse, mood and anxiety disorders. An additional inventory measured the extent to which the patients displayed novelty-seeking traits, characterized by impulsive and risk-taking behavior and excitement in response to new experiences.
"In keeping with our hypothesis, patients with Parkinson's disease who developed pathological gambling when receiving dopamine agonists had a younger age at Parkinson's disease onset, higher novelty-seeking scores, a personal or immediate family history of alcohol use disorders and impaired planning on an impulsivity scale," the authors write. "A robust association was found with medication-induced mania [a psychiatric disorder involving excessive physical and mental activity and impulsive behavior]." Pathological gambling was also weakly linked to younger age, Parkinson's disease that began in the brain's left hemisphere and a high score on a scale measuring the impulsiveness of behaviors
"Screening for such features and advising those at higher risk may be warranted," the authors conclude.
(Arch Neurol. 2007;64:212-216. Available pre-embargo to the media at http://www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
American Medical Association (AMA)
515 N. State St.
Chicago, IL 60610
United States
http://www.ama-assn.org
Behaviors associated with impulse control Including compulsive shopping, hypersexuality, binge eating and pathological gambling have been associated with dopamine agonists, medications used to treat Parkinson's disease. In studies examining the relationship between dopamine agonists and compulsive gambling, the likelihood of gambling problems was unrelated to the medication dosage. This suggests that an underlying trait may interact with the drugs and make an individual more vulnerable to this adverse effect.
Valerie Voon, M.D., National Institute of Neurological Disorders and Stroke, Bethesda, Md., and colleagues compared the characteristics of 21 patients with Parkinson's disease who developed pathological gambling habits after beginning to take dopamine agonists with 42 patients with Parkinson's disease who did not develop compulsive behaviors. The participants, who all visited a clinic in Toronto, Canada, between June 2003 and October 2005, were examined by neurologists and completed assessment scales that measured their levels of impulsivity, substance abuse, mood and anxiety disorders. An additional inventory measured the extent to which the patients displayed novelty-seeking traits, characterized by impulsive and risk-taking behavior and excitement in response to new experiences.
"In keeping with our hypothesis, patients with Parkinson's disease who developed pathological gambling when receiving dopamine agonists had a younger age at Parkinson's disease onset, higher novelty-seeking scores, a personal or immediate family history of alcohol use disorders and impaired planning on an impulsivity scale," the authors write. "A robust association was found with medication-induced mania [a psychiatric disorder involving excessive physical and mental activity and impulsive behavior]." Pathological gambling was also weakly linked to younger age, Parkinson's disease that began in the brain's left hemisphere and a high score on a scale measuring the impulsiveness of behaviors
"Screening for such features and advising those at higher risk may be warranted," the authors conclude.
(Arch Neurol. 2007;64:212-216. Available pre-embargo to the media at http://www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
American Medical Association (AMA)
515 N. State St.
Chicago, IL 60610
United States
http://www.ama-assn.org
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