Miller School Researcher Probes Relationship Between Brain’s Reward System and Teen Depression
Summary
- Miller School researcher Dr. Vilma Gabbay is studying the causes of depression and the urge for suicide in teens.
- Dr. Gabbay found that depressed teens whose left angular gyrus were highly active when presented with unanticipated good news were more likely to report feeling depressed two years later.
- Dr. Gabbay also found that depressed teens had high levels of cytokines and kynurenines, even when they weren’t sick or injured.
Daily living sometimes seems like a never-ending struggle to many teens. But when the dynamic shifts from peer pressure and unhappiness over body image to depression or thoughts about and even attempts at suicide, intervention is needed, and fast.
Vilma Gabbay, M.D., professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine, is committed to understanding what causes depression and the urge for suicide in young people, so she can change the direction of anxious young lives.
“Suicide is the second leading cause of death in this age group. It’s heartbreaking when young people, who have so much to live for, feel compelled to take such a drastic step,” Dr. Gabbay said. “It’s critical that we identify those at risk as early as possible and act to prevent a potential catastrophe.”
Dr. Gabbay is zeroing in on one key factor in depression: anhedonia—the inability to experience pleasure. She has found that anhedonia is tied to a disruption in the brain’s reward system, which itself is linked to feelings of pleasure. Understanding how the reward system works, or doesn’t work, can provide insights into depression and susceptibility to suicide.
What is Depression?
Depression is a mental health disorder marked by feelings of extreme sadness or despondency and an inability to experience happiness or joy. Almost everyone feels sad or down sometime. But depression is more intense and lasts longer.
For researchers to diagnose depression, a patient must show at least five of nine symptoms. One of the symptoms must be sad mood, anhedonia or irritability. This diagnostic scheme makes it hard to find biomarkers and optimal treatments, since each symptom has its own biology.
Anhedonia, is the focus of two pivotal studies by Dr. Gabbay.
Our studies found that problems in the reward system of depressed teens frequently appear early in depression, are associated with worse outcomes over time, entail changes in both brain structure and brain chemistry and are linked to higher levels of inflammation in the body. These findings can help us identify those at risk for depression as well as intervene before things spiral downhill.
Dr. Vilma Gabbary
“Anhedonia refers to loss of enjoyment in activities that were once pleasurable, such as spending time with family and friends, hobbies or social events,” she said. “Our research shows that young people with anhedonia are more likely to struggle with daily activities, suffer longer bouts of depression and are at greater risk for suicide.”
Nearly one in five U.S. adolescents between 12 and 17 years of age report suffering a depressive episode in the most recent year, more than double the 8% figure in 2006.
Moreover, 4% of teens have attempted suicide over the course of their adolescence. This is likely an undercount since it draws on formal, non-anonymous interviews. Young people may feel uneasy making such a sensitive disclosure.
The Why Behind Teen Depression
Dr. Gabbay’s research aims to understand why some teens suffer chronic depression, potentially resulting in suicide attempts, while others recover faster, often with no after-effects.
She’s facing an especially complex task. To date, no single, surefire biomarker for depression has been identified.
Dr. Gabbay’s research utilizes a whole-body perspective, linking the immune system to brain function and specific depression symptoms such as anhedonia. She emphasizes three interrelated approaches. First, she conducts extensive interviews with teens and administers evidence-based tests to assess mood and the possible presence of depression. Each symptom of depression is examined and quantified.
Then Dr. Gabbay examines levels of immune mediators and proteins in the blood. Immune mediators are chemicals that help fight infection but which can contribute to depression. The blood cells are cultured in a lab with an immune stimulator to assess the potential of the immune cells to be activated, mimicking an immune stress reaction in the real world.
Next, Dr. Gabbay carries out non-invasive neuroimaging studies which measure brain function during pleasurable “reward activity” and quantify brain chemicals associated with inflammation. Dr. Gabbay then puts everything together to determine the biology of the depression trajectory.
What Brain Imaging Reveals About Depression
To gain a better understanding of anhedonia and depression, Dr. Gabbay used functional magnetic resonance imaging (fMRI) to examine how different parts of the brain responded when a young person anticipated a reward, received a reward, such as praise for a job well done, or were uncertain if they would receive a reward.
She found that depressed teens whose left angular gyrus was highly active when presented with unanticipated good news were more likely to report feeling depressed two years later. The left angular gyrus is linked to a variety of cognitive functions, including language and memory retrieval.
“Our finding makes sense,” said Dr. Gabbay, “since this part of the brain is also associated with self-reflection and overthinking, which can make it easier to get trapped in negative thoughts.”
She and her team also discovered that teens who had more intense activity in the insula and anterior cingulate were less likely to report feeling joy or being motivated two years later. Among their functions, these two regions of the brain signal pain.
Inflammation’s Role in Teen Depression
In a second study, Dr. Gabbay found that inflammation, which is the body’s attempt to fight injury or infection, plays a part in teen depression.
Some teens diagnosed with depression have higher levels of two immune system molecules in their blood. When these molecules—cytokines and kynurenines—fight an infection or help repair an injury, their numbers rise. When the problem is overcome, the numbers go back down. But Dr. Gabbay found that depressed teens had high levels of cytokines and kynurenines even when they weren’t sick or injured.
“It appears that the elevated, prolonged presence of these two molecules interferes with the production of GABA and glutathione, two key brain chemicals,” she said.
GABA’s functions include calming the brain. Low levels are associated with depression, sadness and anxiety. Glutathione is the major antioxidant in the human body and has many functions, including tissue repair. Lower levels may make the brain more susceptible to anhedonia and depression.
“Taken together, our studies found that problems in the reward system of depressed teens frequently appear early in depression, are associated with worse outcomes over time, entail changes in both brain structure and brain chemistry and are linked to higher levels of inflammation in the body,” said Dr. Gabbay. “These findings can help us identify those at risk for depression as well as intervene before things spiral downhill, possibly preventing extreme behaviors such as suicide.”
Dr. Gabbay’s next research project will examine the effects of cannabis on the brain’s reward system, which is especially timely given the rising use of the drug among teens.
Tags: biomarkers, Department of Psychiatry and Behavioral Sciences, depression, Dr. Vilma Gabbay, Psychiatry and Behavioral Sciences