T

he second decade of life is a time of extraordinary physical, intellectual, and emotional growth. A changing and complex social environment full of new challenges and opportunities help sculpt a young person’s identity, health, and well-being. The brain rapidly adapts in response to these influences. But we don’t really know how it does this, or how genes, hormones, and the environment interact to shape brain development and function.

One way to find out is to use imaging to look at the developing brain while monitoring the many different experiences that could influence it during this crucial period.

We first started discussing the possibility of a large, long-term study of adolescent brain development in 2014 soon after the establishment of the Collaborative Research on Addiction at NIH, a National Institutes of Health partnership established to foster research on multiple substance use. As directors of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, we were mainly interested in how the use of drugs such as nicotine, alcohol, marijuana, and more affect the developing brain.

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With the move by many states to legalize marijuana, the rapid emergence of designer drugs, and new delivery devices (such as electronic nicotine delivery systems), people wanted to know the truth about how substance use affects young brains. Unfortunately, there was only so much we could tell them with confidence.

We already knew that alcohol could harm the brains of adolescent users, but existing brain imaging studies couldn’t answer whether and how marijuana — or even nicotine — affected the developing human brain. And while we knew from some studies that chronic marijuana use by teens is linked to adverse outcomes, like higher rates of dropping out of school, mental health problems, and use of other substances, we still could not say with sufficient confidence whether marijuana causes these outcomes or is just one part of a constellation of risk factors such as genetics, alcohol use, socioeconomic status, and so on. Most of the studies that reported impaired cognition in adolescents who regularly used marijuana did not account for brain function before use or the use of other substances.

We realized that what the world needed was a large longitudinal cohort study that began just before adolescence — before exposure to drugs and alcohol — and that followed the participants through the decade of adolescence and into early adulthood. It would use periodic brain imaging along the way to track the effects of substance use (infrequent or heavy, in different combinations) as well as non-use, along with other environmental variables.

Such a study had never been possible before. But with advances in neuroimaging and the development of big data analytics, it had become thinkable and doable.

As we began planning, we realized that a study of this magnitude could also address many questions far beyond the effects of substance use. It could offer valuable insights into the emotional, cognitive, and academic trajectories that characterize adolescence and help define how they relate to brain development. Mental health problems such as depression and anxiety often begin, or have precursors, during the same time frame, and countless environmental exposures during adolescence may interact with the developing brain as both risk and protective factors for problems.

And with enough participants, we could also look at the effects of socioeconomic and cultural variables, genetic factors, and environmental exposures — ranging from screen time to sleep patterns and extracurricular activities like sports and music — on learning and memory, attention, impulsivity, social engagement, delinquency, and a wide range of other measures that affect health and well-being, such as obesity and head trauma.

And so the Adolescent Brain Cognitive Development (ABCD) study was born. It will track 10,000 youths for a decade, starting at age 9 or 10. Participants will undergo magnetic resonance imaging (a noninvasive procedure that does not expose an individual to radiation) every other year to assess changes in brain structure (brain morphology and structural connectivity) and function (at rest and during a task) as they transition from childhood into adolescence. The volunteers will also be asked to take part in a range of periodic behavioral and neurocognitive assessments, as well as annual interviews, to capture information about physical and behavioral health, school performance, social activities, and other variables.

Using saliva samples and other biospecimens, the ABCD team will assess hormone levels, exposures to environmental toxins, and substance use, as well as gather genetic data. Researchers also plan to recruit 800 pairs of twins to provide a closer look at interactions between genetics and environmental exposures.

The vast amount of data collected will be anonymized to protect participants’ privacy and then made available to other researchers for analysis. These data will inform future projects that we can’t yet envision.

Setting benchmarks

The focus of our two institutes is usually on disorders and the ways brain development can go awry or be compromised. But something we quickly realized when collaborating with our National Institutes of Health partners in designing this ambitious research project was that such a large study could finally give us benchmarks of healthy, normal brain development. No such thing has ever existed.

Consider this: When parents take their child to a pediatrician, the child’s physical development can be plotted and compared to established norms, such as growth curves for height and weight. Just by stepping on a scale and having his or her height measured, much can be determined about how appropriately a child’s physical development is progressing and what health issues might need to be addressed.

The huge amount of data gathered by the ABCD study could potentially give us biomarkers (including neuropsychological markers such as executive function, impulsivity, emotional function, and cognitive capacity) that could serve as indicators of brain development. Pediatricians could use such biomarkers to identify children at risk for depression or ADHD, for instance, as well as for substance use.

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With the wealth of brain imaging data that ABCD will provide, pediatric neurologists will be able to set standards against which to compare the MRI of a teen who has suffered a possible head injury on the sports field to determine the presence or extent of concussion. Such reference points, which don’t currently exist, are sorely needed to help guide diagnosis and treatment.

At this point we do not know what normal brain development looks like at age 10, 12, 14, 16, 18, or 20. Snapshots of healthy brains as they develop throughout this crucial decade of rapid brain changes, along with genetic analyses and detailed information about factors that alter the course of development, will be among the important contributions ABCD will make to science and medicine.

Participants for ABCD are now being recruited through public and private schools near 21 research sites around the country. Ten thousand children — and their families — have an unprecedented opportunity to contribute to our scientific knowledge of the brain and all aspects of health and development during the second decade of life. To learn more about the study, please visit abcdstudy.org.

Nora D. Volkow, MD, is director of the National Institute on Drug Abuse. George F. Koob, PhD, is the director of the National Institute on Alcohol Abuse and Alcoholism.

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