Remitted major depression is characterized by reduced prefrontal cortex reactivity to reward loss

Abstract

Background: Major depression (MDD) is characterized by anhedonia. Although a growing body of literature has linked anhedonia in MDD to reduced frontostriatal activity during reward gains, relatively few studies have examined neural responsivity to loss, and no studies to date have examined neural responses to loss in euthymic individuals with a history of MDD.

Methods: An fMRI monetary incentive delay task was administered to 19 participants with remitted MDD (rMDD) and 19 never depressed controls. Analyses examined group activation differences in brain reward circuitry during monetary loss anticipation and outcomes. Secondary analyses examined the association between self-reported rumination and brain activation in the rMDD group.

Results: Compared to controls, the rMDD group showed less superior frontal gyrus activation during loss anticipation and less inferior and superior frontal gyri activation during loss outcomes (cluster corrected p's<.05). Ruminative Responses Scale scores were negatively correlated with superior frontal gyrus activation (r=-.68, p=.001) during loss outcomes in the rMDD group.

Limitations: Replication with a larger sample is needed.

Conclusions: Euthymic individuals with a history of MDD showed prefrontal cortex hypoactivation during loss anticipation and outcomes, and the degree of superior frontal gyrus hypoactivation was associated with rumination. Abnormal prefrontal cortex responses to loss may reflect a trait-like vulnerability to MDD, although future research is needed to evaluate the utility of this functional neural endophenotype as a prospective risk marker.

Keywords: Anticipation; Magnetic resonance imaging; Major depressive disorder; Remission; Reward; Rumination.

Conflict of interest statement

All authors declare that they have no conflicts of interest.

© 2013 Elsevier B.V. All rights reserved.

Figures

Figure 1

The MID task. Each trial consisted of a cue (i.e., a triangle indicated an incentive trial, a circle indicated a non-incentive trial), an anticipatory delay, a target, and outcome feedback.

Figure 2

Coronal and sagittal images depicting significantly less activation prefrontal cortex activation in rMDD versus controls during (A) loss anticipation relative to non-loss anticipation and (B) loss outcomes relative to non-loss outcomes. Statistical images were thresholded using a cluster corrected significance threshold of p<.05. Coordinates are in Montreal Neurological Institute space. SFG=superior frontal gyrus; IFG=inferior frontal gyrus.

Figure 3

Correlation between activation of the left superior frontal gyrus during loss outcomes and RRS scores in the rMDD group. SFG=superior frontal gyrus.