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Medical News & Perspectives
August 14, 2019

With Neuroimaging, Large NIH Study Could Shine a Light on the Adolescent Brain

JAMA. Published online August 14, 2019. doi:10.1001/jama.2019.9981

Over the coming decade, an ambitious National Institutes of Health–funded study will observe almost 12 000 healthy 9- and 10-year-old children at 21 sites around the country, measuring their mental and physical health and cognition while tracking their brain changes, substance use, digital media habits, and more. The findings should contribute to our understanding of what healthy brain and cognitive development look like, as well as the factors that support or alter that path.

Neuroimaging is a major focus of the Adolescent Brain Cognitive Development (ABCD) study. Scans conducted every 2 years will provide insight into the brain’s structure and function as children age. “Up until recently we haven’t had the technology to be able to image adolescents through this time period on this kind of scale,” said the project’s director, Gaya Dowling, PhD, a neuroscientist at the National Institute on Drug Abuse.

The study’s size and diversity will help to ensure the findings speak to the true makeup of the nation’s youth. The goal was to build a cohort that reflects US demographics in terms of race, ethnicity, sex, and socioeconomic status. “This is really the first study to be able to do that,” Dowling said.

Baseline findings from the full study cohort were released in April, but there’s plenty more data to come. Researchers will continue to meet with participants annually and connect on the phone between visits. In addition to brain and cognitive changes, they also want to identify other healthful trajectories, such as social, emotional, and academic development, as the children transition into teenagers and young adults.

Dowling recently spoke with JAMA about what we can expect to learn from the data, which are being made freely available to researchers. The following is an edited version of the interview.

JAMA:Tell us about the scope of the study. What are some of the key areas of research?

Dr Dowling:We have quite a set of assessments that we are doing with these kids. We collect information on their height and weight and waist measurements. We have an extensive mental health battery. We have a big focus on substance use. We’re also asking a lot of questions about the culture and environment, things like neighborhood and school safety, family environment, acculturation, and discrimination.

In addition to the questionnaires, we have the children undergoing cognitive testing. We’re looking at things like attention and learning and memory, cognitive control, and impulsivity. And then, as I mentioned, we have brain imaging. We’re looking at both structural and functional brain imaging. And then finally we’re collecting some biospecimens. We’re looking at things like pubertal hormones, genetics, and exposure to various substances. One of the biospecimens that we’re collecting are baby teeth to analyze environmental exposures from the second trimester of pregnancy to when the tooth is shed.

The broad array of measures will allow us to understand these developmental trajectories and what factors, both positive and negative, influence them.

JAMA:What are some questions about substance use and addiction you hope to be able to answer?

Dr Dowling:One of the reasons that the study was initiated was because there were so many changes that were going on in the environment that these kids are growing up in. For example, we had a lot of policy changes with respect to marijuana and we had new delivery devices for nicotine. There was little known about what that impact was going to be on adolescents.

But even more specifically, one of the main drivers for the study was to understand the impact of substance use on brain development. Most studies that have tried to answer that question have compared people who have used drugs to those who haven’t used drugs. What that doesn’t allow you to do is see what a person’s brain may have looked like before they started using drugs. By enrolling kids before there’s any substance use, we can see what those changes might be. And that’s really a unique contribution.

JAMA:There’s a lot of concern among parents and physicians and policy makers about increasing legalization of marijuana. Will we know more about what marijuana does to the brain in adolescents thanks to your study?

Dr Dowling:We’re hoping to understand better what the impact of marijuana is on the brain. And we’re also hoping to be able to understand what the impact [of those policies] may be in terms of risk for adolescents. Because we collected data in 21 cities around the country, we have some sites that have enacted legislation to legalize recreational marijuana. We can see whether there may be differential impacts on risks for use based on those policies.

JAMA:The National Academies recently released a report about adolescent development that called for increased access to behavioral health care and treatment. How will your study potentially add to the conversation?

Dr Dowling:If we’re able to document ways that you can identify people at risk prior to them being in crisis so that you can intervene earlier, that could have a huge contribution.

JAMA:What are some of the questions around mental health that you’re going to be investigating?

Dr Dowling:Suicide is a big topic of conversation generally across the lifespan, but particularly with adolescents. We made a point of being sure to ask the children [about symptoms like suicidal ideation] even at these young ages. Those are symptoms that they may not share with their parents. We are also asking questions about anxiety, trauma, and a number of different factors that could influence mental health.

We’re also very interested in the relationship between substance use and mental illness. These are two disorders that generally emerge during adolescence. It’s been very difficult to disentangle which came first. Is somebody self-medicating a mental illness and that’s why they’re using a substance? Or does early substance use contribute to the development of a mental illness? ABCD is in a unique position to answer questions like that because of the longitudinal nature and large size of the study.

JAMA:Tell us more about the brain imaging.

Dr Dowling:We’re doing structural [magnetic resonance imaging] (MRI) looking at how the brain structure develops over time during this period. We’re also doing functional MRI, which will allow us to see the activity of the brain and the connections between regions of the brain and how that develops over time. We do that in two ways. One is using resting-state functional connectivity, where we’re looking at the brain at rest and how parts of the brain are interacting with each other as they’re going through these developmental stages. The other is to do task-based functional MRI, where we have the kids do a test in the imager and record the activity associated with them doing those tasks.

We’re hoping that the structural piece will give us some sort of guidance for pediatricians to understand what the traditional healthy trajectory looks like, so that if a child is not meeting that trajectory they can be identified. For example, there’s a lot of concern about concussions. But when a kid has a sports injury and has an MRI done, there’s nothing to compare that against because they’ve most likely not had one when they were healthy. We’ll be able to have something that pediatricians can compare against.

We don’t have a good understanding about brain correlates of some mental health disorders. A recent paper that came out of ABCD has identified some potential [brain imaging] markers [for psychosis] risk. All of this is very preliminary at this point. We need to follow these kids over time to see what that means. But it’s an example of what ABCD might be able to do.

JAMA:Are you planning to study screen time?

Dr Dowling:We ask about TV, movies, video games, social media, cell phone use, texting. We ask about these separately so that we can see whether a video game has a different impact than social media does. It’s also likely that you’re going to see different impacts on different kids depending on how they use them. So I think we’re going to need to drill a little bit deeper as the study moves forward to be able to disentangle what those effects might be.

JAMA:What do you hope to learn about social media’s effects on youth?

Dr Dowling:Social media’s a tough one because it’s constantly changing, and so measuring use keeps us on our toes. At our baseline interview we had very basic questions about digital media use. More recently we’ve added some questions about how their use of social media impacts their lives. Does it affect their sleep? Does it affect their relationships? How do they feel when they are without their phone? Questions that can get more at that compulsive nature of the interaction with their devices.

The great thing about ABCD is because we’re already collecting all of this other information about mental health and physical health and brain activity, we can relate those questions to that data and then get a better sense of whether the time that they are spending using these digital devices is impacting those other factors. The average child gets their own cell phone around the age of 10 in the United States. While there was some cell phone and social media use at baseline we expect that to go up dramatically, so we’ll be able to look at this prospectively.

JAMA:Some researchers will use cell phones and wearables to collect data on digital device use and other metrics, correct?

Dr Dowling:Yes. We are definitely hoping to involve new technologies as they emerge. Technology is going to be changing over the course of the study and we need to be able to incorporate that as we move forward. We have just recently rolled out Fitbit data within the study. We’ll be collecting information about activity and sleep and heart rate for all of the kids over a 3-week period.

We’re also in the process of piloting a way of measuring objective cell phone use. We have some data based on self-report about how much time kids spend on their phones. But they notoriously under report that, so we would really like to have objective measures of how much time they spend on their phones, how much time they spend on social media vs games vs texting.

There’s also been discussions about wearables that can detect substance use. Those things aren’t quite ready for prime time in ABCD but we are exploring a lot of different possibilities.

JAMA:Quite a few studies already have been published using ABCD data. Are there any highlights for you?

Dr Dowling:Some papers have come out on the first 4500 participants or so. They show the promise of ABCD for the future rather than anything terribly definitive at this stage. But they do raise some very interesting findings. A paper that recently came out found that participation in team sports predicted fewer depressive symptoms only in boys and not in girls. They also found that there were some brain differences that seem to mediate this [effect]. There may be many reasons that those [sex] differences exist. It could be pubertal development at this age. It could be the culture around sports participation being different for boys than girls.

Right now we’re just seeing associations and we don’t really know what they mean yet. But it does point to very interesting things for us to follow up as we continue to collect data from these kids.

JAMA:What’s your aim in making all of the ABCD data freely available to researchers?

Dr Dowling:This is one of the most exciting parts to me. It’s a wonderful data set and it’s incredibly rich. But it’s so rich that the ABCD investigators themselves would not have enough time in their lifetimes to analyze all of the data. Any investigator around the world can request access to it through the NIH data archive. This gives us an opportunity to have many, many more questions than even we envisioned answered. It also allows for improvement in rigor and reproducibility.

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