Searching for associations: New Waisman investigator studies child behavior disorders and the genetics and environment behind them

Adityarup “Rup” Chakravorty, Waisman Communications

James J. Li, PhD
James J. Li, PhD

James Li’s drive to research, understand and develop effective interventions for childhood behavioral disorders, such as attention deficit hyperactivity disorder (ADHD), was sparked in the hallways of a juvenile justice center in Baltimore.

As a sophomore at Johns Hopkins University, Li would shadow public defenders and listen to cases of children who were in trouble with the law.

“I soon realized that many of these children had mental health issues, such as ADHD, autism spectrum disorder (ASD) and depression,” says Li. Without adequate care and effective interventions and therapies, several of the children wound up being repeat offenders. The time Li spent at the justice center fueled a determination to help children battling these mental health challenges.

“That’s what really drew me to clinical psychology; I can not only research and understand these psychiatric challenges but also apply my findings clinically,” says Li, “and that’s what I hope to do here at the Waisman Center.”

Looking beyond a single gene

Li, an assistant professor in the Department of Psychology, joined the Waisman Center in July 2015. Much of Li’s research involves searching for the genetic causes of different childhood behavioral disorders, such as ADHD. He uses what are called genome-wide association (GWA) scans, which allow scientists to assemble a more complete picture of how multiple genes may be contributing to different disorders instead of focusing on a single gene.

“More and more we are realizing that one gene usually has a very small effect,” says Li. “Behavioral disorders are complex and it’s unlikely that we will find only one or two genes responsible for them.”

To discover the bevy of genes playing a role in a particular disorder, GWA studies involve large numbers of people divided into two groups: one group that has the condition or disorder being studied and another ‘control’ group that does not.

Researchers compare the DNA sequences of individuals belonging to the two groups and use statistical analyses to identify the differences that are significant. Once the genes containing significant differences in their DNA sequences are identified, researchers can start to piece together how they are linked to specific disorders.

For example, several genes connected to how the body reacts to dopamine—a molecule that plays important roles in the human brain—are also related to the functioning of a part of the brain called the basal ganglia, which is connected to motor activity and voluntary movements.

“Hyperactivity and impulsivity seen in individuals with ADHD are also linked with motor activity and movement,” says Li. Understanding the network of genes related to dopamine may ultimately yield valuable insight into symptoms and treatments for ADHD.

Li doesn’t limit his research to GWA studies performed by his laboratory. The results of GWA studies from different institutions, often involving thousands of individuals, are frequently available to researchers across the world. Li uses these results to frame and direct his research into uncovering the genes responsible for various behavioral disorders.

Nature + Nurture

Our genetic makeup is just one part of what makes us unique individuals. The environment we grow up in and live among also plays a vital role in defining our sense of self and influencing our mental states.

“Genes and environments don’t just interact with one another, they also correlate with one another,” says Li. An individual’s genes can often influence what environments he or she seeks out, just as environmental factors can affect how our genes function.

“A good example would be that if you carried risk-genes for anti-social or oppositional behavior, you are also more likely to seek peers who are deviant,” says Li. This amalgamation of genetic and environmental causes of a behavioral disorder makes it challenging for researchers to discern individual factors connected with the disorder.

Studies conducted in an environment controlled by the researchers can help. For instance, in a laboratory, “there is no way that a child has selected the environment because the researchers are the ones who have manipulated it,” says Li. Keeping the environment constant allows researchers to test how effective different therapies and interventions are for children who have the same behavioral disorder but may have different genetic makeups.

Precision medicine

Ultimately, Li wants to identify biological markers and environmental risk factors that will allow him to do more targeted or precise interventions.

“There are more than 120,000 ways in which you can meet the diagnostic criteria for ADHD,” says Li, “and that means the likelihood that any child who walks into a clinic has the same signs as another child who has been diagnosed with ADHD is 1 in 120,000.”

That also means that identifying a single risk factor or a single intervention that would be effective for several children is unlikely. According to Li, “we need to do a better job with precision diagnosis and precision treatment.”

Effective research studies in developmental psychopathology and precision treatments can no longer involve only one field, such as genetics or behavior, according to Li. They have to integrate several other disciplines, such as neuroimaging to look at the brain and physiological studies to look at stress and hormone levels. “There are so many different units to consider today,” he says, “that it’s not just X and Y, but X and Y and Z and then A and B and C!”

Li thinks of the Waisman Center as a citadel for multidisciplinary research. “Being at the Waisman Center is a tremendous asset because I have access to some of the foremost experts in—for example—neuroimaging and behavioral genetics by just walking down the hall,” he says.

To learn more about Li’s research, please visit the Social and Behavioral Development lab.