Where's the fun in that? Broadening the focus on reward function in depression.

In the search for the neural substrates of depression, some recent work has suggested that the disruption of reward processing occurs as part of the essential pathophysiology of the disorder. Depression has long been conceptualized as a disorder of dysregulated positive affect and unusual reward processing (1), and affective neuroscience findings have begun to support this perspective. Research on reward represents a shift away from a focus primarily on aspects of depression related to negative affect and threat processing. More important, this research direction could offer the potential to develop treatments that target reward-related circuits and thereby offer hope to those who exhibit dysfunction in those circuits. The literature on reward functioning and depression is not without its contradictions, however, and much remains to be understood. Three approaches are relevant for elucidating the role of reward processing in depression: 1) taking a developmental perspective; 2) developing ecologically valid, consistent measurement techniques; and 3) identifying interindividual variability in reward functioning to improve treatments. To summarize the current literature, research in several areas indicates that dysregulation in the processing of rewards—or stimuli that inspire behavior and reinforce it after it occurs—could play a pivotal role in affective, behavioral, and physiologic aspects of depression. Phenomenologically, people with depression experience dampened positive affect and reduced motivation, and they engage less frequently in behavior likely to lead to the achievement of goals or experience of pleasant emotions. Anhedonia, which reflects difficulty with anticipating and enjoying pleasant events, is commonly experienced, with up to 76% of adolescents with major depressive disorder reporting the symptom (2). Behaviorally, during the anticipation or receipt of reward, adolescents and adults with depression exhibit difficulty applying a flexible approach to making decisions or responding under varying conditions. Depression has been linked to disrupted signaling in the dopamine neuromodulatory system, which plays an important role in reward-related affect and behavior through projections from the midbrain to the striatum and prefrontal cortex. Specifically, animal research, postmortem studies, pharmacologic studies of response to psychostimulants, and studies of receptor binding all point to the possibility of reduced dopamine transmission in depression (3). Similarly, animal studies manipulating brain-derived neurotrophic factor in dopamine pathways further implicate the dopamine system in depression-relevant behaviors (4). Physiologic findings on reward processing in depression have not been consistent, partly because methods differ widely and are rarely compared directly. Some studies have reported that people with depression exhibit reduced brain reactivity to rewarding stimuli in the striatum, a region traditionally associated with pleasant mood. However, results have differed in terms of direction of depression effects, methods used to measure reward processing, and brain regions where differences are evident. Paradigms employed include physiologic (e.g., functional magnetic resonance imaging tasks) and pharmacologic challenges (e.g., dopaminergic probes). Physiologic paradigms focus on various experiences, including decision making, responding under time pressure, receiving performance feedback, viewing words or pictures, and recalling autobiographical events. In addition to the striatum, the brain regions in which depression effects are reported for reward functioning include the orbito-frontal cortex, anterior cingulate cortex, and amygdala. Until consistency of methods improves, it will be difficult to draw conclusions about the presence and extent of reward dysfunction in depression.