Researchers Hope Long-Term Study Yields Clues to Mysterious Disorder--Autism

Researchers Hope Long-Term Study Yields Clues to Mysterious Disorder--Autism

Apr 4, 2004 6:00 PM

The University of Utah School of Medicine is one of 10 major U.S. medical centers selected to participate in a multidisciplinary research network studying one of medical science's most mysterious disorders--autism.

The National Institute for Child and Human Development (NICHD), sponsor of the study, designated the U of U as one of 10 Collaborative Programs of Excellence in Autism (CPEA) sites to study the disorder. The University group is studying three aspects of autism: genetics, immunology, and brain development (neuroimaging). The U is the only CPEA in the Intermountain Region and one of two sites between the East and West coasts, according to Janet E. Lainhart, M.D., associate professor of psychiatry and the study's co-principal investigator. William M. McMahon, M.D., associate professor of psychiatry, is principal investigator.

For neuroimaging of brain development, U researchers will follow 72 children and adults with autism, as well as a control group of 72 people without autism. The study will follow children with autism into adulthood to track brain development. Participants will receive a magnetic resonance imaging scan (MRI) and clinical neuropsychological assessment at the beginning of the study and another three years later.

The University's new $3 million MRI scanner, the Magnetom 3T Trio System, will play a key role in monitoring brain development of individuals with autism, said Lainhart, who's also leading the neuroimaging aspect of the study. One of the most sophisticated MRI scanners in the world--and the only one in Utah--the 3T provides images twice as clear and detailed as most MRIs and will allow researchers to track minute changes in brain development over a period of years.

"It is quite clear from our work to date, and the work of other investigators, that the key to the neurobiology of autism and brain mechanisms involved in autism lies not in how the brain looks at any one time," Lainhart said. "Rather, the key lies in how the brain changes over time."

Autism is a disorder of early brain growth and function that impairs basic aspects of social, language, and communication development. Mental retardation is associated with the disorder, but autism occurs at all IQ levels, even into the 140s. One-third of children with autism do not speak, and the disorder can be difficult to diagnose before age 2.

The number of people with autism in the United States is not known, but the disorder is estimated to occur in two to six people per thousand, according to the Centers for Disease Control and Prevention.

Other than increased brain size in young children with autism, there are no major structural differences between the brains of people with autism and those who develop more typically. This leads researchers to suspect the brains of children and adults with autism have other problems.

"The current thinking in autism is that some areas of the brain are not communicating properly," Lainhart said. "It's like areas of the brain are normal in size and shape, but the wiring between some parts is not right."

With the 3T's powerful resolution, the U researchers are going to track minuscule changes in the brain development of people with autism. Sophisticated image analysis methods will demarcate the gray and white matter of the brain and map changes in the size and shape of brain regions over time. 3T brain image data on children and adults will be combined and then brain volume and gray and white matter will be statistically compared between autistic children and adults and those who are developing normally.

Employing diffusion tensor imaging, a technique that uses the dispersal of water molecules through cells, the researchers will look closer at the white matter in the brains of study participants. Gray matter consists of neuron cell bodies and is located on the surface of the brain in the cortex and deep in the brain. These cell bodies send out white matter fibers, or axons, that connect different parts of the brain and allow them to communicate. Diffusion tensor imaging allows much more detailed study of white matter, including how fibers are organized.

"The exquisite quality of 3T images lets us look closer and better at brain development in autism," Lainhart said. "There is no doubt we will learn much more about autism with the 3T scanner than was possible in the past."

As information is gathered, U of U researchers hope it will help them put together a clearer picture of autism that may lead to therapies to treat or even change the course of the disorder.

"The time is ripe," Lainhart said. "Most researchers are optimistic and hopeful that within the next 10 years--maybe within five--we'll have a much better understanding of autism."

Diffusion tensor imaging has potential applications for other disorders and diseases, such as strokes, multiple sclerosis, amyotrophic lateral sclerosis (Lou Gehrig's Disease), tumors, and spinal cord injuries.

The neuroimaging study is a collaborative effort, drawing on researchers from the U School of Medicine's departments of psychiatry, neurology, and radiology, as well as the University's Scientific Computing and Imaging Institute. Colleagues from the University of Wisconsin School of Medicine, Andrew Alexander, Ph.D., and Mariana Lazar, Ph.D., and Brigham Young University, Erin Bigler, Ph.D., are collaborating with the U researchers.

Two other components of the Utah research are also extremely important.

Hilary Coon, Ph.D., research associate professor of psychiatry, is principal investigator for the genetics study. The genetics study seeks to collect blood on 800 Utah families that have an individual with autism, including large families with multiple relatives who have autism.

Robert S. Fujinami, Ph.D., professor of neurology and principal investigator of the immunology component, is determining if there are immunological mechanisms involved in autism. The genetics and immunology data will be combined with the brain imaging data for an integrated study of autism.

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