Combining results from 628 children's brains, this MRI scan shows regions activated as faces are viewed (yellow and orange) and other areas (blue and cyan) activated during a demanding working memory task.

RICHARD WATTS AND HUGH GARAVAN

Huge study of teen brains could reveal roots of mental illness, impacts of drug abuse

Chya* (pronounced SHY-a), who is not quite 10 years old, recently spent an unusual day at the University of Maryland School of Medicine in Baltimore. Part of the time she was in a "cool" brain scanner while playing video games designed to test her memory and other brain-related skills. At other points, she answered lots of questions about her life and health on an iPad.

A slender Baltimore third grader who likes drawing, hip hop, and playing with her pet Chihuahua, Chya is one of more than 6800 children now enrolled in an unprecedented examination of teenage brain development. The Adolescent Brain Cognitive Development Study—or ABCD Study—will complete its 2-year enrollment period in September, and this month will release a trove of data from 4500 early participants into a freely accessible, anonymized database. Ultimately, the study aims to follow 10,000 children for a decade as they grow from 9- and 10-year-olds into young adults.

Supported by the first chunk of $300 million pledged by several institutes at the National Institutes of Health (NIH) in Bethesda, Maryland, teams at 21 sites around the United States are regularly using MRI machines to record the structure and activity of these young brains. They're also collecting reams of psychological, cognitive, and environmental data about each child, along with biological specimens such as their DNA. In addition to providing the first standardized benchmarks of healthy adolescent brain development, this information should allow scientists to probe how substance use, sports injuries, screen time, sleep habits, and other influences may affect—or be affected by—a maturing brain.

"A lot of studies in this area are plagued by the fact that we tend to capture teenagers after they have already started to misbehave in various ways. So, the fact that we are following kids from … before they engage in a lot of risk-taking behavior—it's going to be an incredibly rich data set," says clinical neuroscientist Monica Luciana of the University of Minnesota in Minneapolis, an ABCD Study site where she is a principal investigator (PI).

Clarifying the impacts of alcohol and drug use is a key goal for the study's leading funders: the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both in Bethesda. "There is an urgency to try to address these questions," says NIDA Director Nora Volkow, the prime mover behind the study. The recent legalization of recreational marijuana in several states makes the study especially timely, she argues.

Other studies have used MRI to follow teen brain development. Europe's IMAGEN enrolled 2000 14-year-olds and scanned them at intervals over the past decade. And NIAAA has been funding a study of alcohol's impacts, imaging the brains of more than 800 youths once a year for 4 years. But ABCD "is going to be by far the largest," Volkow says. "It's [also] longer-lasting, starts younger, and is much more comprehensive" in terms of testing.

Every 2 years, researchers will image the brain structures of Chya and other subjects, and record their neural activity as they perform tasks involving memory, rewards, and face recognition. Every year, the participants will have their height, weight, and waist measured, and answer questions designed to assess psychological symptoms. They will also be asked annually about environmental influences—things like family conflict and neighborhood crime.

The study aims to describe a normal trajectory of adolescent brain development—similar to the height and weight charts in pediatricians' offices—and use that to begin to answer the many chicken-and-egg questions that correlational studies can't. For instance, people who smoke marijuana heavily beginning in adolescence or young adulthood show markedly less connectivity between the neuronal axons of the hippocampus, a brain region important to long-term memory formation and learning, than do nonusers. But were the users' brains wired differently to begin with, leading them to smoke cannabis heavily? Or did the smoking cause the changes?

"At age 9 and 10 you can get a nice clean baseline assessment on these kids," says Hugh Garavan, a neurobiologist who is the PI at the ABCD Study site at the University of Vermont (UVM) in Burlington. "Then, when someone develops psychosis at 16, we can go back and look at their brains and psychological assessments at 9, 10, 11, and 12. Were there markers of risk there?"

Such markers, it's hoped, will ultimately allow much earlier diagnosis, treatment, or prevention of substance abuse, mental illness, and other conditions. A key strength of the study is that it will enroll enough children—including 800 pairs of twins—to answer questions that require large numbers of subjects, such as whether there are age windows when the brain is particularly vulnerable to use of a given drug.

The study intends to reflect the United States's socioeconomic, geographical, racial, and ethnic diversity. Planners want the study pool to be 6% Asian-American, 16% black, and 24% Hispanic. As of early January, with 8 months left in recruitment, they are falling short on Asian-American and black enrollment, at 2% and 12%, respectively, but were close to meeting the Hispanic target, at 22%. And the "other" category, which includes mixed-race kids and Native Americans, accounts for fully 11% of enrollees, more than double the organizers' 5% target.

The ABCD Study crystallized at an inauspicious time. In May 2014, when its planners held their first meeting, the National Children's Study, an NIH effort to follow 100,000 children from the womb to age 21, was collapsing as a result of daunting logistics, overambitious objectives, and a projected cost of more than $3 billion. "We were very, very aware, because of the Children's Study, that we didn't want to load up the Christmas tree with too many ornaments," recalls George Koob, NIAAA director since 2014.

By September 2016, under a tightly designed protocol dictated by the attention spans and wiggles of 9- and 10-year-old children, the ABCD Study was enrolling. The organizers are assuming 15% of the planned 11,500 enrollees will drop out over the decade, leaving the desired 10,000 participants. Some fear that may be optimistic, but Garavan is bullish. "Because it's a longitudinal study, we have to make sure the kids enjoy the experience," he says.

Garavan has succeeded with at least one recruit. "You had to drool into two vials, not spit. And it was fun," recalls Afton, who had his brain scanned at UVM last September, a day before his 10th birthday. "Eventually they are going to learn how to track if someone has depression or something else, or not, by just looking at their brain in an MRI machine. I thought that was cool. And I wanted to help."

Chya, for her part, left the Baltimore study site last month with a picture of her brain and an ABCD T-shirt. She plans to return at the same time next year.

*The ABCD Study keeps participants anonymous; the families of the kids in this article allowed the use of their first names.