Research Frontiers: Piecing Together the Mystery of Autism

Courtney
Jolley
Kennedy Krieger takes a multifaceted approach to investigating this complex disorder

The Maloni BoysMore than 25,000 children will be diagnosed with autism spectrum disorders this year a number greater than AIDS, diabetes, and cancer combined yet so many aspects of the disorder remain a mystery. Is its cause genetic, environmental, or some combination of factors? Are dietary changes and drugs the best hope for treatment, or should the focus remain solely on behavioral interventions?

The questions are endless, largely due to the complexity of this disorder. "Autism is classified as a pervasive developmental disorder," says Dr. Gary Goldstein M.D., president of Kennedy Krieger Institute. "That means it hits you deep and covers a great deal of territory, unlike something like a spinal cord injury or cerebral palsy, which can be devastating, but which are fairly discrete in terms of cause and progression."

At Kennedy Krieger, a remarkable variety of disciplines have allied in the mission to better understand and treat autism, which affects approximately one in 166 children and impairs the ability to communicate, understand language, play, and interact with others.

"In our current research efforts, we have geneticists and physicians focused on metabolic disorders, while at the same time physicists, motion-analysis experts, speech-language pathologists, and psychiatrists committed to investigating other aspects of autism," Goldstein explains. "Many of these experts have formed very unusual partnerships to consider different elements of the disorder."

A central component of the Institute's autism research efforts is the Interactive Autism Network (IAN), an unprecedented national database with the potential to transform autism research not just at Kennedy Krieger, but at institutions worldwide. With the help of a $2.26 million grant from Autism Speaks, the nation's leading nonprofit organization focused on autism research, IAN will serve as a shared resource for families and individuals with Autism Spectrum Disorders (ASD), connecting them with other families and autism researchers throughout the world. In time, IAN will facilitate improvements in research, and allow families affected by autism a voice in developing the scientific and policy questions to be investigated.

"One of the biggest challenges in advancing autism research is finding enough appropriate subjects for your investigations," Dr. Goldstein admits. "We may have 1,000 families in our programs, but once you start eliminating children with other conditions, outside of certain age groups, or an entire gender to meet the criteria for your study, you may be left with 10 children, which isn't a large enough pool. But if this database includes 100,000 children and families, that should make a tremendous difference on research at all institutions and help interested families find a research program that's right for them."

Even without the benefit of a program like IAN, researchers at Kennedy Krieger are making great strides in improving their understanding of autism's causes, progression and treatment.

Current research highlights include the following:

  • A recent article in the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) confirmed a link between low cholesterol levels and ASD.

Led by Kennedy Krieger psychiatrist Dr. Elaine Tierney and Dr. Richard Kelley, a pediatric metabolic disease expert, the study builds on earlier research involving children with Smith-Lemli-Opitz syndrome, a rare metabolic condition characterized by an inability to make cholesterol, which is often marked by symptoms of autism. Drs. Tierney and Kelley discovered that cholesterol supplements reduced the incidence of autistic behaviors in this population. Nineteen of the children had cholesterol levels lower than those found in 99 percent of children. This raises the possibility of a possible genetic link between cholesterol deficiencies and symptoms of autism, as well as potential drug or nutritional interventions.

  • A landmark study of younger siblings of children with autism revealed a high risk for recurrence within families and distinct markers for the disorder in children as young as 12 months.

Speech-language pathologist Dr. Rebecca Landa has been following the younger siblings of children with autism for more than seven years. In a June article published in the Journal of Child Psychology and Psychiatry, she documented statistically significant differences by 14 months of age when comparing children who were diagnosed as having ASD at three years of age to children without delays. By 24 months of age, she detected differences between children with ASD, children with language delays, and children having no delays. Knowing that some children with ASD show clear developmental disruption as early as 14 months of age, paves the way for earlier detection of ASD, which usually is not diagnosed until age three or four. Earlier detection leads to earlier intervention, which may lead to improved outcomes in individuals with ASD. In addition to her work with early detection, Dr. Landa and one of her staff, Dr. Katherine Holman, have been helping Baltimore County public schools incorporate the strategies of her Achievements intervention program in a classroom setting. This is a groundbreaking step in autism treatment, notes Dr. Goldstein, because the large number of children diagnosed with autism precludes most of them from receiving treatment at specialized centers.

  • In an Annals of Neurology article coauthored by Kennedy Krieger pediatric neurologist Dr. Andrew Zimmerman, pathology reports on the brains of deceased individuals with autism demonstrated nearuniversal evidence of chemical inflammation.

These results, which indicate that immune pathways may be activated in the brains of people with autism, reveal a new potential avenue of study for the causation of autism. For many years, Dr. Zimmerman and others have noted anecdotally that individuals with autism seem to have a greater-than-average family history of autoimmune diseases such as lupus and rheumatoid arthritis. Their initial research may support additional investigation of this connection, and open up new possibilities for pharmaceutical treatments.

These projects represent the breadth, but not the depth, of Kennedy Krieger's current autism research efforts. Other Kennedy Krieger researchers are hard at work investigating the links between motor learning deficits and characteristics of autism, the presence of low serotonin levels in the mothers of children with autism, and the factors that lead children with developmental disorders like Fragile X syndrome to also receive autism diagnoses. The scope of autism-related research at Kennedy Krieger demonstrates the commitment of a tremendous variety of experts, some from fields that very rarely collaborate, who have joined together in the fight to improve the lives of children with autism and their families.

For more information on autism research at Kennedy Krieger, please visit www.kennedykrieger.org or call 1-888-554-2080.