By Adityarup “Rup” Chakravorty
For Waisman investigator and clinician Janet Lainhart, research and patient care are inextricably connected.
“I have been caring for children, adolescents and adults with autism spectrum disorder (ASD) since 1990,” says Lainhart, who is a professor of psychiatry at the University of Wisconsin-Madison and a psychiatrist in the Waisman Center Autism and Developmental Disabilities Clinic.
And in her time in different clinics, Lainhart noticed that some individuals would show improvement in their ASD symptoms and overall functioning while others would not improve and some would get worse. “We had no idea why,” she says.
So Lainhart set out to find some answers.
The first clues
“For many years, people thought that variations in brain development that lead to ASD happened before birth,” says Lainhart, “and nothing major changed after that.”
But Lainhart’s early research suggested atypical brain growth and development after birth seemed to be important in autism.
“We knew that the brain continues to develop and maturate in typically developing individuals until about 27 years of age,” she says. But what happens in the brain in individuals with ASD as they grow older remained unknown.
So Lainhart started one of the first studies exploring how the brain develops over time in people with ASD from 3 years of age into mid-adulthood.
That study, initiated in 2002 while Lainhart was at the University of Utah, has become “the longest ongoing study combining clinical, biological, and psychological evolution of ASD in young people over time,” says Lainhart.
Traffic in the brain
One of the goals of the study is to discover how genetic variations in young people with ASD are related to brain changes that lead to clinical symptoms of the disorder, such as impaired social interaction and repetitive behaviors.
“If you think about it, in between genes and clinical symptoms [of ASD] are changes in brain development,” says Lainhart. “Genes first impact brain development, and as a result of changes in how the brain develops, there are clinical manifestations of what we recognize as ASD.”
To study brain development in young people with ASD, Lainhart connected with other researchers first at Utah and then at the UW-Madison Waisman Center.
Andrew Alexander, also an investigator at the Waisman Center, was one of the first researchers to collaborate with Lainhart on the ASD study.
One of Alexander’s areas of expertise is in brain imaging techniques, including a technique called diffusion tensor imaging, or DTI. Using this technique has had major ramifications in Lainhart’s, and her colleagues’, quest to better understand how the brain develops in children with ASD.
“If you use regular MRI to scan the brain of a child with severe ASD, the great majority of time that scan looks typical,” says Lainhart.
But differences start to show up when researchers use DTI to study the brain.
“DTI allows us to go beyond mapping just the size and shape of structures in the brain,” says Lainhart. “Using DTI, we can study white matter connectivity within and between various brain structures. That’s important because we now know that brain connectivity is significantly impacted in ASD.”
Imagine a city with miles of roads connecting different hubs. How well the city functions depends on the speed and efficiency of traffic flow in the city, which in turn depends on how the roads are built, how coordinated traffic patterns are, and so on.
Similarly, optimal brain functioning depends on how efficiently nerve cell messages travel throughout the brain, and the speed at which information from different parts of the brain can get from one place to another in a coordinated fashion,” says Lainhart.
Lainhart’s goal is to understand differences in how parts of the brain grow, develop, and communicate in individuals with ASD and in typically developing people. “We also want to know how these differences evolve over time and how they are related to the clinical course of ASD,” she says. “We want to understand what is going on in the brains of individuals with ASD who show improvements over time and those who do not.”
A dream to help
Lainhart and Alexander are working with molecular geneticists, including Steve Schrodi at the Marshfield Clinic, to use the variations in brain connectivity in individuals with ASD to drive the discovery of new risk genes that may be involved in the disorder.
They are developing a new collaboration with Waisman investigators Qiang Chang and Xinyu Zhao to eventually study the effect of new ASD risk genes in actual nerve cells and other state-of-the-art laboratory models.
“The goal is to understand the biology of ASD at the genetic, molecular, cellular, developmental, clinical, and functional level in each individual who is affected,” says Lainhart, “because autism in each individual is both similar and different from autism in another individual.”
Understanding how each individual with ASD is different can help design more effective interventions. “Each person is genetically and biologically unique,” says Lainhart,” and if we can understand this uniqueness in the context of ASD, then we can individualize therapies for each person and optimize outcomes.”
Lainhart credits her collaborators—some of whom she has worked with for decades—for much of the research success and potential.
“No single scientist can do what we do in his or her own lab alone,” says Lainhart. “Although I helped assemble it, I am but one part of this group of scientists with multidisciplinary backgrounds.”
And this collaboration has continued. “Our initial group came together in the late 1990s, and additional people have joined over time, but we still video-conference every Friday,” says Lainhart.
It all comes back to the clinic
For Lainhart, her work in the clinic with children and adults with ASD and their parents is critical. “Being with the young people, being with their parents, hearing right from the front lines what the challenges are and how autism manifests in and impacts each individual and family, that is entirely what drives my research,” she says.
Lainhart’s research also fuels her work in the clinic, she says, because “to carry on effective research you have to stay at the forefront of the field.” Lainhart reads extensively about new research every week, which she says enhances her ability to provide clinical care based on the current understanding of autism.
“For research to be clinically relevant and have maximal translational impact, I believe there needs to be a marriage between research and clinical care,” says Lainhart. “The two are intricately linked; each informs and brings out the best in the other.”
By combining research and clinical care Lainhart hopes to unlock the biological underpinnings of ASD, and then use that knowledge to identify exactly which intervention or therapy will be most effective for each person with ASD.
“I wake up every morning saying it needs to happen and it needs to happen soon,” says Lainhart. “You have to have hope, you have to believe it can happen, and you have to be a very good problem solver, listen to young people with autism and their families, work with lots of wonderful collaborators, and never give up.”