Autism Remains a Mystery, But Help May be on the Horizon

WASHINGTON, July 29 -- The American Association for the Advancement of Science issued the following news release:

Renee and Barry Gordon are the parents of Alex, 22, a profoundly autistic young man. He is unable to reliably dress himself, give himself a shower, brush his teeth, wash his face or do many other daily tasks of living. He doesn't recognize dangers such as moving cars and hot stoves. He has never spoken a word.

And yet he can read, and type, and operate a computer. He can communicate by typing his wishes into an iPhone that hangs around his neck and speaks what he has typed. Raising Alex has been an incredible challenge, Renee Gordon told a AAAS-organized briefing on autism. But it also has been a rewarding story of love, patience, and adaptability by Renee, a lawyer for the Small Business Administration, and Barry, a behavioral neurologist at Johns Hopkins Medical Institutions whose expertise includes disorders of speech, language, and memory.

"It was beyond irony when our son proved to be unable to speak and unable to learn," Barry Gordon said, recalling the realization that Alex was not meeting simple developmental milestones even at 6 months old, and then failed to meet other milestones such as speaking.

Renee stopped work to help identify and coordinate therapies for Alex. The couple enrolled him in a school for autistic children at the Kennedy Krieger Institute in Baltimore and became deeply involved in designing a behavioral intervention program that, over the course of 15 years, has given Alex the ability to do simple but important communication tasks such as ordering a meal at a restaurant and the ability to participate in community activities such as visiting museums and attending live performances. He also has displayed a degree of socialization and can interact with housemates at a group home.

Speakers at the 17 July Capitol Hill briefing, hosted by AAAS through the support of the Dana Foundation in conjunction with Rep Chaka Fattah (D-Pa.), discussed advances in the diagnosis of autism spectrum disorder (ASD), which can range from mild difficulties in social interaction and behavioral impairments to profound conditions such as Alex Gordon's inability to speak. The speakers also discussed current standards of care for autism, including intensive behavioral intervention as soon as possible (an approach the Gordons embraced even before Alex was formally diagnosed); and research on treatment approaches, including drugs that might improve the chemical signaling abilities of neurons in the autistic brain.

Autism remains one of the most poorly understood of the neurological disorders, and the number of cases is on the rise. According to a March estimate by the Centers for Disease Control and Prevention, about 1 in 68 children in the United States is affected by autism spectrum disorders, up from the previous estimate of 1 in 88 reported in 2012. The criteria used to diagnose ASD and the methods used to collect data had not changed, the CDC said.

The uptick in the reported incidence of autism "is an issue of concern, and we're not sure what's going on," said briefing moderator Alan I. Leshner, chief executive officer of AAAS and formerly director of the National Institute on Drug Abuse and deputy director of the National Institute of Mental Health.

Catherine Lord, director of the Center for Autism and the Developing Brain at New York-Presbyterian Hospital, Weill Cornell Medical College and Columbia University Medical Center, said the rising prevalence of autism is partly explained by more public awareness and improved diagnosis over a broad range of autism-related disorders. Yet there remain discrepancies in reported autism prevalence from state to state, Lord said, and inequities in resources devoted to diagnosis and treatment of the disorder. "There are many things that are not at all fair about what's going on," Lord said. In states with lower prevalence rates, she said, it is likely there are autistic children who simply are not being identified. "There's no reason to think they don't exist," Lord said. "They are just not being found."

Researchers have not been able to pinpoint the causes of autism, although both genetics and environment likely play a role. The search for a single gene that causes autism has turned up instead dozens of genes associated with the disorder -- most of which are quite rare or for which the association may be quite weak and dependent on multi-level interactions. Many of the genes also are linked to other conditions such as schizophrenia and attention deficit hyperactivity disorder (ADHD).

"There isn't an autism gene," Lord said. "There isn't going to be an autism gene."

Researchers also have been studying possible environmental factors such as advanced parental age at time of conception, maternal illness during pregnancy, and certain difficulties during birth, particularly those involving periods of oxygen deprivation to the baby's brain. (Despite considerable public attention, research studies and expert panels have found no link between vaccines and autism.) As with genetics, no single environmental factor is likely to explain the wide variety of autism spectrum disorders, scientists say.

When it comes to treatment, early use of intensive behavioral therapy remains the current standard of care and must be made available to all children with ASD, said Diane Chugani, professor of pediatrics at Wayne State University and director of the Translational Imaging Laboratory at Children's Hospital of Michigan in Detroit. Medications also can be used to help reduce symptoms such as repetitive behaviors, anxiety, and aggression.

The traditional view has been that drug treatments cannot change or cure the underlying neurological disorder, Chugani said, a view that she says may be outdated. Animal studies suggest there may be ways to reverse neurological deficits associated with autism-related disorders such as Rett syndrome and tuberous sclerosis complex, according to Chugani, and there could be common neurochemical features associated with many genes implicated in autism.

"The place where communications happens in the brain is the synapse," Chugani said, referring to the small gap at the end of neighboring neurons where chemical signals are transmitted.

"There are numerous genes involved in synapse formation and function," she said, and many different proteins are involved in the signaling process, including serotonin and other important neurotransmitters.

"The drugs of the future are going to target the synapse," she said. Chugani has done positron emission tomography (PET) studies of serotonin synthesis in children with autism and has found differences in developmental changes in serotonin synthesis in the brains of young autistic children compared to non-autistic children. Based upon these results, she and her colleagues conducted a clinical trial on a drug called buspirone that mimics serotonin in young autistic children. The preliminary findings led to additional funding from the National Institute of Neurological Disorders and Stroke for further testing. The ultimate goal is to provide a more normal modulation of brain development in young children with autism.

The emerging understanding of how genetic variability affects the synapses and communication among brain cells should prove to be "a rich source of new drug treatments for ASD," Chugani said. She predicted that genetic testing, use of biomarkers in the blood, and brain imaging methods will help clinicians determine which treatments are most appropriate for individuals with autism at different stages of their development. "I think we are on the threshold of some very interesting results," Chugani said.

Lord was more guarded in her outlook. "We don't have any biological markers," she said. "We have a lively, interesting, wonderful background of neuroscience that is moving forward, but it has basically had no practical result, I would say, in the last 20 years."

There remains a need for faster, more effective screening of children for autism spectrum disorders, Lord said, and active, early involvement by parents is essential. "We can do a very good job" of diagnosis, she said, but it requires time and input from both the parents and skilled clinicians. Lord helped develop the gold-standard diagnostic tools for autism called the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R).

Lord noted a need for more trained providers, especially those willing to take insurance. Her group opened a clinic in New York that does take insurance, she said, and "we have a thousand people in a year contacting us wanting assessments because there is no place else where people will take insurance."

Lord also called for "a more rational scientific agenda where we integrate medical findings into clinical practice. Right now, that's very random. People hear about something and they try it."

Better coordination of basic research and health care services will help families who must bear the real burdens of coping with autism, Lord said. Barry Gordon echoed her sentiments, as both a clinician and a parent. "I have to treat people in the here and now," he said.

As a researcher, he said, he can appreciate the need for long-term basic research on the biological underpinnings of autism. As a parent, he is looking for quicker translation of research findings into the clinical setting. "As a parent, I want it now," Gordon said.

[Category: Science]

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