People who are depressed very often show reduced interest in experiencing or obtaining pleasure, a symptom called anhedonia that research has traced to dysfunction in the brain’s reward system.

In adults and adolescents, blunted responses in a part of the brain called the striatum correlate with depression, and have also been found to predict vulnerability to later depressive episodes. Possibly related to these facts is the observation that even when depression is in remission, circuitry involved in the reward response continues to display a blunted level of reactivity. This raises the question of whether blunted reward response is a marker of past depression as well as a risk factor or even a predictor of depression.

Two members of BBRF’s Scientific Council, Deanna Barch, Ph.D. and Joan Luby, M.D., both of Washington University, St. Louis, are trying to learn more about the precise ways in which depression impacts the brain’s reward areas and circuits that connect them. Dr. Barch is a 2013 BBRF Distinguished Investigator, 2006 Independent Investigator, and 2000 and 1995 Young Investigator. Dr. Luby is a 2008 and 2004 BBRF Independent Investigator, 1999 Young Investigator and 2004 recipient of BBRF’s Klerman Prize for Exceptional Clinical Research.

For years Drs. Barch and Luby have been studying depression in young children and following them into adolescence—research with the potential to reveal things that cannot be detected in studies conducted at a single point in time. In the American Journal of Psychiatry, they and colleagues including first author Brent Rappaport recently reported new findings from their long-running study of early-onset depression, and they pertain directly to the question of how the reward system is affected in the illness.

The team noted that their early-onset depression sample of 306 children of preschool age (3-6) presented a “unique opportunity” for testing an important prediction: that in people with current depression and those with a history of chronic depression—especially, perhaps, depression that begins in the preschool years—the brain’s reward areas and related circuitry are affected in different ways.

The team tested this prediction using functional MRI scanning in young people with early-onset depression—now adolescents—participating in the ongoing study. Brain imaging in the study cohort began once the children reached school age (8-14 years old). Over the years, some children were added to the study to provide the contrast of “healthy controls”—children without a psychiatric diagnosis. The study just published included 131 adolescent participants, 109 of whom had been recruited as depressed preschoolers.

Study participants performed a card-guessing monetary-reward task used to assess neural reactivity to both the anticipation of a reward and the receipt of reward feedback, which involve distinct brain operations.

Imaging results revealed something about young people that has already been discovered in adults: the severity of “current” depressive symptoms is associated with blunted response in a specific brain area: the ventral portion of the striatum. In contrast, “cumulative” depression—i.e., its impact in people who have suffered depression symptoms chronically, over time—is associated with the dysfunction of broad circuitry in the brain connecting parts of the cerebral cortex and the striatum.

“Global blunting of the cortico-striatal circuit could represent a risk factor for chronic or recurrent depression,” the team concluded, “and may be associated with early-onset and [other] more severe forms of depression.”

The cause of this broad, circuit-based blunting of the reward response is not known. But the team proposes that it could represent either damage to the network incurred even before the onset of depression symptoms, or it may “represent a scar” left by being in a state of chronic depression. “With repeated exposure to depressive symptoms, particularly early in life, the cortico-striatal circuit may not develop properly,” the researchers said.

The research also shed new light on distinctions in the brain between anticipating a reward and actually receiving one. Blunted reactivity to anticipating rewards “may represent deficits in learning about cues that predict reward,” the team noted. Or, they said, it may reflect an inability to actually represent in one’s mind what the experience of a reward might be like.

The implications: the team’s findings suggest the possibility that instead of causing a failure to experience pleasure from rewards, chronic depression experienced over childhood might cause a reduced motivation to experience reward, perhaps caused by blunted reactivity of the striatum and related brain regions.

In distinguishing neural contributions to current depression and cumulative depression, the team suggested that “unique neurodevelopmental processes may be in play." They will focus on these in continuing research, hoping such knowledge will facilitate the creation of new depression interventions for patients of all ages.