New research published in AJP in Advance on June 18 has uncovered a wealth of new information on how the brain responds to rewards during the onset of depression.
“For a long time now, people have thought that alterations in the reward pathway are quite integral to depression, and there has been some very nice evidence presented in this regard,” said Argyris Stringaris, M.D., Ph.D., head of the Mood and Development Lab at King’s College London and lead author on this study.
However, Stringaris noted that there are many crucial gaps in our knowledge. “For example, there has been little research to test the plausible hypothesis that reward abnormalities are linked to anhedonia.”
So Stringaris and colleagues throughout Europe initiated an ambitious study that assessed the brain activity of 1,576 adolescents (all about 14 years of age) using functional magnetic resonance imaging (fMRI) while they performed an incentive-based game. The participants were tested twice, once at the start of the study and again two years later.
With regard to the anhedonia hypothesis, the team found that teens who reported having anhedonia had lower activity in their ventral striatum—an important reward center in the brain—than those without anhedonia. Low mood was not associated with any changes in reward activity, but if teens had both symptoms, they had an even greater decrease in activity, though it was limited to the right half of the ventral striatum.
What’s more, they observed that reward processing decreased on a gradient when comparing healthy teens, healthy teens with anhedonia, teens with subthreshold depression, and teens with clinical depression.
“We have this idea that depression, like many other psychiatric conditions, operates along a spectrum, and this shows that some of the underlying mechanisms also follow that spectrum,” Stringaris told Psychiatric News.
But while reward changes and clinical depression followed a similar path, the big question is, Which is leading what? Results at the two-year follow-up found that lower baseline activity in the ventral striatum in healthy teens did increase the risk of developing either subthreshold or clinical depression.
Taken together with the other findings, Stringaris believes that changes to the ventral striatum might indeed be a part of depression’s causal chain. “And while not a diagnostic marker by itself, if you had a teen showing other risk factors for depression, assessing the teen’s reward processing could add to your predictive value.”
Erika Forbes, Ph.D., an associate professor of psychiatry, psychology, and pediatrics at the University of Pittsburgh, applauded this study for its size and rigor but urged caution before looking too deeply into the results.
“These findings provide some meaningful answers at the group level, but I would not see them as conclusive for any individual,” she said. “People who have depression can have a range of different experiences and alterations in different brain circuits or regions.”
“Another important aspect to consider is that the teenage brain is still developing, and there would be many changes in brain function expected between 14 and 16 years of age,” she continued. “We still have a lot to learn about the course of normal development and the mutual influence of brain development and depression.”
Stringaris agreed that there are more experiments to do.
“The most important thing we should do is an intervention, and during the intervention see what happens to the reward system,” he said. “In other words, if you successfully treat anhedonia or depression, do you see changes in the reward pathway?”
Some preliminary work suggests the answer is yes, though Stringaris believes that more thorough studies, particularly with newer antidepressants, would help inform treatments for depressed teens.
This study was supported by the European Union-funded projects IMAGEN, IMAGEMEND, and the Innovative Medicine Initiative Project, among several others. ■
“The Brain’s Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample” can be accessed
here.