Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation

Abstract

Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.

Conflict of interest statement

Conflict of interest statement: N.H.K. is a consultant related to the development of psychotropic agents (or serves on the Scientific Advisory Board) for the following companies: Astra Zeneca, Bristol-Myers-Squibb, CeNeRx Biopharma, Corcept, Cyberonics, Forest Laboratories, General Electric Corp., Jazz Pharmaceuticals, Eli Lilly, Neuronetics, Sanofi Syntholabs, and Wyeth Pharmaceuticals (which funded this study). N.H.K. has stock options in Corcept and CeNeRx and is principal owner of Promoter Neurosciences.

Figures

Fig. 1.

Activation in nucleus accumbens (NAcc) shows specific decrease for individuals with depression. (A) Depressed show a specific decrease from first to second half of scan session (P < 0.05 corrected; k > 50 voxels) in the NAcc. (B) For depressed, less change in left NAcc activity is associated with greater self-reported positive affect. (C) Depressed patients show a decrease in NAcc activity, across time, in the Enhance vs. Suppress contrast. (D) Depressed patients show a decrease in NAcc activity, across time, in the Enhance vs. Attend contrast (error bars, standard error of mean).

Fig. 2.

Time courses of activation in nucleus accumbens ROI for controls and depressed, first and second half of scan session for the “enhance,” “attend,” and “suppress” conditions. Gray box denotes regulation period.

Fig. 3.

For depressed patients, the greatest decrease in NAcc activity across time occurs to the enhance condition. Greater values indicate a greater decrase in activation from first to second half. Across the three conditions, the Group × Condition interaction was significant [F(2, 42) = 5.01; P = 0.01]; the MDD group also showed a significant linear trend across conditions [F(1, 76) = 6.77; P = 0.01]; controls did not (F < 1). Pairwise t tests for the MDD group were significant in the Enhance vs. Attend [t(25) = 2.60; P = 0.015] and Enhance vs. Suppress [t(25) = 3.09; P = 0.005] contrasts, there were no significant pairwise contrasts for the controls. Significant group differences were also found in the Enhance [t (43) = −3.86; P < 0.001] and Attend [t(43) = −2.59; P = 0.01] conditions such that the MDD group showed a greater decrease in NAcc activity from first to second half than controls. Error bars indicate SEM. *, P < 0.05; **, P < 0.01.

Fig. 4.

Connectivity analysis indicating reduction of LNAcc/L MFG connectivity as a function of time (P < 0.05, small volume corrected; k > 15 voxels). Error bars indicate SEM.