“Reaching In, Reaching Out: Autism in America”

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Back in the 1940s and 1950s, the conventional wisdom about the cause of autism was simple: it was entirely the mother’s fault. “It must have been really horrific for the mother to go through that — not only to deal with this child, but to also be blamed for it,” says Gene Blatt, a School of Medicine associate professor of anatomy and neurobiology, who specializes in autism research. By the late 1960s, researchers had started talking about its being a biological disorder, “but we didn’t have the tools to study it,” says Helen Tager-Flusberg, a MED professor of anatomy and neurobiology and director of the National Institutes of Health Autism Research Center of Excellence at BU.

In the 1980s, two BU professors, Margaret Bauman and Thomas Kemper, pioneered neuropathological studies in autism and saw abnormalities in the brains of autistic adults. That pointed the way to a crucial finding: autism is a neurological disorder.

Blatt and his colleagues are continuing Bauman’s and Kemper’s work in the MED Laboratory of Autism Neuroscience Research, where the two researchers are still active members. Using postmortem specimens from the Harvard Brain Tissue Resource Center, they are finding evidence that the changes in the autistic brain appear to be directed toward particular systems, or parts, of the brain. New research, funded by a grant from the Nancy Lurie Marks Family Foundation, focuses on areas responsible for speech and language.

“We look at the neurotransmitters and their receptors in the brain,” Blatt says, “to see their localization and see how it may be different in autism.”

He and his colleagues began publishing their research, which showed the role of a particular receptor, GABA, in autism, in 2001. “We’ve followed that since then, and it’s almost like anywhere we look in the brain where neuropathology has been described, we see GABA receptor changes,” Blatt says. “It’s more extensive than that, but this is one of the players.” GABA is a chemical messenger distributed widely in the brain. An inhibitory receptor, it reduces the activity of the neurons to which it binds.

Some researchers think one of GABA’s purposes is to modulate information processing throughout the brain. How GABA works, says Blatt, is complex, but it seems to help the brain maintain a delicate balance between excitatory and inhibitory input into neurons. “If you disturb that balance, you will potentially alter the firing and the outcome from that brain area,” he says. When inhibitory receptors like GABA are reduced, as they are in autism cases, there is greater potential for increased excitation, throwing off the delicate balance.

Blatt hopes to create a model of all these mechanisms, incorporating their GABA findings, and to make predictions about what goes wrong in particular areas of the brain in autism, based on altered connectivity and neurochemistry. “It’s a real challenge for us,” he says, “but we are making much progress.”

Building a model, he admits, is a long way from medical intervention, but it’s a helpful first step. “By having an understanding of when these changes occur and what receptors might aid in therapeutic intervention,” he says, “we could target those specific transmitter types rather than giving medication that is simply controlling behavior.”

In other words, “instead of, ‘Johnny is agitated, he’s aggressive, so let me give him something to quiet down,’ you could potentially provide pharmacotherapeutic intervention to actually target the problem,” Blatt says. “Clinically that’s important.”

Because the brain is known to have great plasticity, researchers are hopeful. The brain’s adaptability explains why the earlier the diagnosis of autism, the greater potential there is for help, says Blatt.

Tager-Flusberg agrees. “The interventions for very young children are enormously effective in reducing symptom severity,” she says. “In our longitudinal study we see children making huge gains, especially in language, which is so central — gains we wouldn’t have seen earlier.”

Nancy Wiseman (COM’81), the author of Could It Be Autism? (Broadway Books) whose daughter was diagnosed with autism at age two, concurs, based on her daughter’s experience and that of others she’s seen. “The earlier you intervene the better the outcome is. But recovery is a tricky word. I never use the word cure; at this point, there is no cure,” she says. Still, there is hope that autistic children can adapt and lead better lives than they otherwise would. “I like to say that a child can lose his or her diagnosis,” Wiseman says.

Click here to read part one of “Reaching In, Reaching Out: Autism in America.”

Taylor McNeil can be reached at tmcneil@bu.edu.

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