An fMRI study of reward circuitry in patients with minimal or extensive history of major depression.

Functional abnormalities in regions associated with reward processing are apparent in people with depression, but the extent to which disease burden impacts on the processing of reward is unknown. This research examined the neural correlates of reward processing in patients with major depressive disorder and varying degrees of past illness burden. Twenty-nine depressed patients and twenty-five healthy subjects with no lifetime history of psychiatric illness completed the study. Subsets of fourteen patients were presenting for first lifetime treatment of a depressive episode, and fifteen patients had at least three treated episodes of depression. We used functional magnetic resonance imaging to study blood oxygen level-dependent signals during the performance of a contingency reversal reward paradigm. The results identified group differences in the response to punishers bilaterally in the orbitofrontal and medial prefrontal regions. In addition, areas such as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices were activated greatest by controls during reward processing, less by patients early in the course of illness and least by patients with highly recurrent illness-suggesting that these areas are sensitive to the impact of disease burden and repeated episodes of depression. Reward processing in people with depression may be associated with diminished signaling of incentive salience, a reduction in the formation of reward-related associations and heightened sensitivities for negatively valenced stimuli, all of which could contribute to symptoms of depression.