Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder

Abstract

Objective: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures.

Method: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes.

Results: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally.

Conclusions: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.

Trial registration: ClinicalTrials.gov NCT00183755.

Figures

FIGURE 1

Behavioral findings during the monetary incentive delay task in MDD (N=30) and comparison (N=31) subjects. (A) Reaction time (in ms) in response to the target as a function of reward, loss, or no-incentive cue. (B) Reaction Time difference scores (no-incentive - reward cue; no-incentive - loss cue) reveal significantly reduced relative reaction time speeding in MDD subjects for reward trials (p<0.047) and a similar trend for loss trials (p=0.053).

FIGURE 2

Reward-related anticipatory activation in MDD (N=26) and comparison (N=31) subjects. Coronal (A) and axial (B) slices showing anticipatory reward activity [Reward cue - No-incentive cue] in basal ganglia regions are shown for both comparison and MDD subjects, as well as for the random effect analyses comparing the two groups. (A) Robust activation of ventral striatal regions, including the nucleus accumbens, is seen in both groups, leading to a lack of group differences. (B) Relative to comparison subjects, the MDD group shows significantly reduced activation during reward anticipation in the left putamen (x=-28, y=-13, z=-2). All contrasts are thresholded at p<0.005. Pt = Putamen, L = Left

FIGURE 3

Reward-related consummatory activation in MDD (N=26) and comparison (N=31) subjects. Coronal slices showing consummatory reward activity [Gain feedback - No-change feedback] in basal ganglia regions are shown for both comparison and MDD subjects, as well as for the random effect analyses comparing the two groups. Relative to comparison subjects, the MDD group shows significantly reduced activation in response to gain feedback in the (A) left nucleus accumbens and (B) bilateral caudate. Follow-up analyses on beta weights extracted from the (C) nucleus accumbens and (D) bilateral caudate regions (averaged across three clusters) indicated that group differences were specific to reward outcome. All contrasts are thresholded at p<0.005. NAcc = Nucleus Accumbens, Cd = Caudate, L = Left

FIGURE 4

Relationship between clinical symptoms and caudate volume among MDD subjects (N=26). Scatterplot and Pearson correlation between residualized right caudate volume (adjusted for age and gender) and (A) total BDI score (r=-0.579, p<0.002); and (B) anhedonic BDI subscore (r=-0.635, p<0.0001) among MDD subjects. Similar correlations emerged for the left caudate (total BDI: r=-0.489, p<0.015; anhedonic BDI: r=-0.553, p<0.004). The anhedonic BDI subscore was computed by summing item #4 (loss of pleasure), #12 (loss of interest), #15 (loss of energy), and #21 (loss of interest in sex). Cd = Caudate.