Predicting Depression in Teens

You only need to read the headlines to know the toll the last few years have taken on adolescent mental health. With the stress of the pandemic impacting well-being—and parents left unsure how to help—the search for more timely diagnoses and effective treatments takes on new urgency. For years, psychiatry has focused on mood as the main culprit in depression, but researchers have started to also suspect that motivation is just as important. Randy P. Auerbach, PhD, associate professor and David Pagliaccio, PhD, assistant professor in the department of psychiatry at Columbia University, are co-leading a study that looks at the role that dopamine, which is linked to motivation, may play in depression.

Pre-pandemic, a significant portion of U.S. teenagers were already struggling with depression. “About 20% of adolescents will experience a depressive episode by age 18, and nearly 80% of individuals who experience depression onset in adolescence will have another episode within five years,” says Auerbach. To directly address these alarming figures, Auerbach and Pagliaccio have launched an ambitious and innovative project that aims to identify brain markers that contribute to the unfolding of depression symptoms as well as predict relapse. If successful, this research could change how depression is diagnosed and treated in adolescents.

The Morgan Stanley Alliance for Children’s Mental Health, an initiative created by the Morgan Stanley Foundation to address stress, anxiety, depression and other mental health issues in children and young adults, has partnered with the Columbia University Department of Psychiatry at the Vagelos College of Physicians and Surgeons to facilitate such ground-breaking research. “As mental health challenges amongst children and adolescents are rapidly becoming more pervasive and more urgent, we firmly believe there is not only an opportunity, but an obligation for the private sector to play a critical role in improving children’s mental health,” says Joan Steinberg, President of Morgan Stanley Foundation and CEO of the Alliance for Children’s Mental Health. 

Auerbach and Pagliaccio’s unique study shifts the focus from one key neurotransmitter, serotonin, to another, dopamine. Most people commonly identify the former with depression due to the popularity of selective serotonin reuptake inhibitors, such as fluoxetine and sertraline, a class of antidepressants that help regulate moods. But some mental health experts believe that dopamine—the same neurotransmitter your brain produces when you indulge in your favorite ice cream or win at blackjack—may be at least as important when it comes to understanding and managing depression.

The so-called dopamine hypothesis posits that reduced dopamine activity in the brain is closely linked to lack of motivation, which is a hallmark of depression.¹ It’s worth noting that antidepressants (including those that primarily target other neurotransmitters like serotonin or norepinephrine) seem to work, at least in part, by regulating dopamine activity.

Measuring dopamine levels, however, can be tough. It requires invasive procedures, such as lumbar punctures, to extract spinal fluid to test for the chemical. Auerbach and Pagliaccio believe they may have a solution.  “Neurotransmitters fire to an area of the brain called the midbrain, which influences motivated behavior. And every time they fire, they cast off waste,” Auerbach explains. In the case of dopamine, that byproduct is neuromelanin. A critical goal of their study is to show that neuromelanin, a brain pigment that can be easily measured using noninvasive imaging tests, is a reliable proxy for the presence of dopamine. The study will use magnetic resonance imaging (MRI) to measure neuromelanin levels in adolescents when the study begins and at various predetermined intervals throughout the year.

The study has begun enrolling participants in two groups. One group will include 60 adolescents with at least one depressive episode (defined as meeting the diagnostic criteria for clinical depression for at least two weeks) but are currently in remission. The other group will comprise 60 teens with no personal history of depression.

And while parents are often concerned about how much time teens spend on their smartphones, these devices will play an important role in collecting study data beyond the MRIs. Participants will use an app called Effortless Assessment of Risk States (EARS), downloaded to their personal smartphones, to answer questions periodically about the state of their mental well-being; the EARS app would also collect passive data that will provide researchers with objective information about their daily habits.

“It allows us to capture what adolescents are doing every day,” says Auerbach, who explains that accelerometry data will reveal how physically active participants are, while geolocation data will provide insights about where and how they spend most of their time. The app also scans for patterns of words and phrases used while texting. Auerbach hopes that this information—which the participants consent to share—will lead to more objective ways to detect emerging depression, and that the final results might pave the way for more effective treatments. That might include app-based therapies to nudge teens to tweak certain habits (like sleep more or see friends more often) if they seem to be veering toward a depressive episode—something parents aren’t always aware of.

Findings might also lay the groundwork for new antidepressants that directly target dopamine. “We don’t really have a first-line depression treatment that does that,” says Auerbach. Thanks to his work and the support of the Morgan Stanley Foundation, new treatments for this debilitating disorder may be on the horizon.

¹ https://www.sciencedirect.com/science/article/abs/pii/0924933896851868