Oblivious to the dreary rain pounding on the window, two-year-old Tyler sits, contented, among heaps of brightly-colored plastic, his eyes widening at the sight of unfamiliar toys. As he lunges for a rubber ball rolling down a yellow, plastic slide, a woman walks into the room.
“Ready to go?”
Immediately, a toothy grin breaks out on Tyler’s chubby face. Slapping his hands and thumping his knees on the carpet, he crawls over to the woman, plops down in front of her pointy-toed shoes and looks up expectantly. One would think only a mother would be able to get a child so readily leave his toys. But this woman is not Tyler’s mother. It is Anna Krasno, a research fellow of the Developmental Disabilities Clinic in the Yale Child Study Center.
A silly smile plastered across his face and his blue eyes still wide with excitement, Tyler is carried into an adjacent research room. No lab coats or test tubes; simply a baby seat, a TV, a computer and a screen separate the researchers from the child.
To Tyler, his time in the room is just an extension of his playtime. For YCSC researchers, however, Tyler — and, specifically, his eye movements — is fodder for ground-breaking research on autism.
Tyler settles into a car seat, mesmerized by Elmo on the screen in front of him. The lights grow dim and Elmo is replaced on screen by a series of clips of motherly actresses. They speak in high-pitched voices, play peek-a-boo, and sing songs. Tyler, in return, laughs and giggles, especially enjoying “Old McDonald Had a Farm.”
The procedure used in the experiment is known as eye-tracking, a technique that allows researchers to follow and record a child’s visual movements, said Ami Klin, director of the Autism Program at YCSC. The procedure can give researchers early clues about their likelihood of developing autism, he explained.
Autism is a highly genetic brain development disorder with a wide range of possible symptoms, including impaired social skills and repetitive behavior. Research using the eye-tracking technique has shown that the amount of eye contact a child makes with other people can predict his or her placement on the autism spectrum, Klin said. Those who completely avoid eye contact with the woman on the screen are the most severely autistic, he explained.
Using a beam of infrared light, the computer detects the reflection of the TV screen on the child’s cornea and simultaneously tracks the pupil’s motions. These two measurements are then combined to locate the baby’s gaze and quantify how often the child focused on the actress’s eyes.
The babies in these particular eye-tracking studies were recruited from birth and flagged as being high-risk for autism because they have an autistic sibling. The children are then followed until the age of three, when a firm diagnosis can be given. Their eye-tracking data is then split into two groups, autistic and non-autistic children, for comparison.
This technique may point to signs of autism earlier so that the disease can be diagnosed at an younger age, said Katarzyna Chawarska, an autism researcher at YCSC and head of the Developmental Disabilities Clinic for Infants and Toddlers.
“We’d like to intervene as early as possible so we can minimize the effects that are impinging upon the developing brain,” she said. “Once we have this information, we’ll be able to design treatments that are focused on infants and the mechanisms that inhibit basic social cognitive processes from occurring.”
But research is only half of the equation at the Yale Child Study Center. Combining both research and clinical services is at the crux of YCSC’s mission, Klin said.
“The interrelationship between clinical work and research is what makes us unique,” he said. “There’s a great sense of pride in playing both sides of the equation, both providing high standards of care and advancing the field of knowledge in a relevant way to those that we are treating.”
A recent therapy the YSPC developed will treat tic disorders in children via a behavioral approach, circumventing the need for medication.
“We were looking for an alternative to medication for treating tics,” Diane Findley, Coordinator of the Tic Disorder/Obsessive Compulsive Disorder specialty clinic at YCSC, said. “Most people assume that since tic disorders are biological they can only be fixed through biology. This research is showing that changes can be brought about without medication.”
Patients afflicted with tic disorders acknowledge they have some control over their tics, Findley said, but it’s the urge that precedes the tic that is involuntary, she said. Findley and her researchers built upon this finding to develop a technique that involves teaching patients to carry out a competing task when they experience an urge to tic. For example, if a patient feels an impulse to jerk his neck, deliberately holding his chin down or tightening his neck muscles could distract him from that urge and prevent the tic from occurring.
Molecular biology as it relates to therapeutic advances, too, has a place at the YCSC. Paul Lombroso, a child psychiatrist and director of the molecular neurobiology section of YCSC, spends his days in a more traditional lab setting, where he studies the neurobiology of memory.
His recent work focuses on a protein called STEP that is integral to the elusive process of consolidating short-term memories into long-term memories. An excess of STEP in the brain removes important receptors on neural synapses involved with learning and memory, Lombroso said, lowering an individual’s ability to encode long-term memories.
This excess of STEP has been linked with two major disorders, Alzheimer’s disease and fragile X syndrome, a syndrome relevant to children that shares many of the core symptoms of autism, Lombroso said. Lombroso’s lab was the first to identify this unlikely connection between Alzheimer’s disease and fragile X syndrome and is now working on developing therapeutic tools to reduce levels of STEP in afflicted individuals.
“We’re trying to find small molecules that block the actions of STEP,” Lombroso said. “Hopefully we’ll be able to use it to stem the tide of Alzheimer’s.”