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New Insights Into Major Depression

Dopaminergic inputs to the ventral striatum are one of the brain mechanisms thought to play a role in major depression. However, a recent study reported no major alterations in these inputs in participants with major depression in a non-learning context.

Major depression is a devastating mood disorder with a lifetime prevalence that is higher than 20% in the United States. Major depression is thought to cause disruption of the reward circuits in the brain, leading to impairments in the processing of reward and emotions. The ventral striatum is a specific region of the brain that plays a major role in this brain reward circuitry. Much of the input to the ventral striatum is dopaminergic, meaning that the neurotransmitter dopamine helps the brain region to function.

These dopaminergic inputs represent reward prediction errors (RPEs). RPEs represent the difference, or discrepancy, between a predicted reward and a reward that is currently being experienced during a particular event. These RPEs allow for the consistency of reinforcements. For example, when the outcome of a decision exceeds expectations, there is an increase in the value associated with that outcome. This makes it more likely for that outcome to be chosen again! Because RPEs play a role in adaptive behavior, understanding how they work is critical to understanding major depression, and may help explain the atypical behaviors often seen in individuals with this mood disorder.

Dopaminergic inputs to the ventral striatum are thought to go awry in major depression. In fact, neuroimaging studies have shown reduced activity of the ventral striatum for both the anticipation and the receipt of rewards in both adults and adolescents with major depression. Furthermore, the ventral striatum consistently exhibits decreased RPEs in patients with major depression during reinforcement learning. However, it remains unknown whether depression decreases RPE signals in tasks that are not associated with learning. Therefore, Rutledge and colleagues examined whether major depression would reduce RPE signals in the ventral striatum in a non-learning task. They also examined the emotional impact of RPEs in depression.

The study, published in a recent issue of JAMA Psychiatry, consisted of a group of 52 participants that were exposed to functional magnetic resonance imaging (fMRI) in order to assess the activity of the ventral striatum. Another group of 74 participants were exposed to a risky decision task, in which participants also had to rate their happiness during the task, in order to measure momentary mood. The task involved monetary gambling. These 74 participants performed the task in a laboratory; another groups of 1833 participants used a smartphone-based platform to complete the risky decision task.

The main finding was that participants with moderate depression did not show reduced RPE signals in the ventral striatum compared to individuals without depression. This finding went against what the authors predicted, and is inconsistent with the results of other research. “We found no evidence for impairment in basic reward-related neural and emotional processes in depression in a non-learning context,” the authors stated. They added, “Our results suggest that the dopaminergic RPE signal is not fundamentally affected by depression.” In addition, baseline mood parameters were correlated with depressive symptoms, suggesting that measuring momentary mood may be a useful tool for looking at changes in depressive symptoms over time.


Written by Liana Merrill, PhD

Reference: Rutledge, R.B. et al. (2017). Association of Neural and Emotional Impacts of Reward Prediction Errors With Major Depression. JAMA Psychiatry.



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