Tackling Teenage Depression: $4 Million NIH Grant Supports Search for Biomarkers for Severe Depression

November 10, 2020—(BRONX, NY)—According to the National Institute of Mental Health (NIMH), in 2017 approximately 13% of adolescents in the United States, or 3.2 million children aged 12 to 17, had at least one major episode of depression. While many recover from such an episode, a significant portion will develop severe depression or a chronic mood disorder. There is an urgent need to identify adolescents who are at higher risk for serious problems and may benefit from aggressive treatment.

In an important step toward that goal, researchers at Albert Einstein College of Medicine and Montefiore Health System have received a five-year, $4 million grant from the NIMH, part of the National Institutes of Health, to search for the biological factors that predict duration and severity of depression in adolescents, with the goal of improving clinical care.

Vilma Gabbay, M.D.

Vilma Gabbay, M.D.

“Just because depression is common among teens doesn’t mean it isn’t serious,” said Vilma Gabbay, M.D., associate professor of psychiatry and behavioral sciences and in the Dominick P. Purpura Department of Neuroscience at Einstein. “Depression can result in death by suicide. We are trying to predict which teens are likely to develop severe and/or sustained depression so that we stave off devastating outcomes.” Dr. Gabbay is also a clinical psychiatrist at Montefiore and co-director of the Psychiatry Research Institute at Montefiore Einstein (PRIME).

The Biology of Depression

Depression is a mental health disorder characterized by persistent feelings of sadness or irritability and the loss of interest in activities once enjoyed. It is poorly understood biologically and has a range of possible causes, including genetics, stressful life events, and medical problems.

“In psychiatry, you diagnose from symptoms, but that can be subjective,” explained Dr. Gabbay. “Our lab has focused on looking at depression through the neurobiology of symptoms so we can find more objective criteria. It’s like trying to determine if a tumor is benign or malignant—we need a way to accurately determine how serious an individual’s disease is to use the most effective treatment. This would have an enormous impact on millions of children, their families, and futures.”

The Pleasure Principle

In her previous research, Dr. Gabbay showed that anhedonia, or the inability to feel pleasure, is associated with poor outcomes for adolescent depression, including suicide. Her lab studied the reward circuitry in the brain and found that lower levels of ACC GABA—a neurotransmitter linked to the reward circuit—were associated with worse anhedonia two years later.

We are trying to predict which teens are likely to develop severe and/or sustained depression so that we stave off devastating outcomes.

Vilma Gabbay, M.D.

The immune system also influences the reward circuitry. Previous research has shown that inflammation—both in the brain and throughout the body—is associated with the development of anhedonia and depression.

Predicting Outcomes

In the new study, Einstein-Montefiore researchers will collaborate with the Nathan S. Kline Institute for Psychiatric Research to enroll a diverse group of 120 adolescents with depressive symptoms and follow them over two years.

The teens will undergo a comprehensive clinical evaluation, and those diagnosed with depression will take computerized tests designed to engage and measure the reward circuitry. Researchers will look for known biomarkers of inflammation and measure participants’ ACC GABA levels. They also will conduct functional MRI on the teens during the reward testing to evaluate their ability to feel pleasure, along with depression severity, functioning, anxiety, and their risk of suicide.

“Ideally, this project will not only identify the teens who need more significant help with their depression, but may also point the way toward new drugs to treat the disease,” said Dr. Gabbay.

The grant is titled “Biobehavioral Predictors of Illness Progression in Adolescent Depression” (R01MH120601).