Meta-analysis of reward processing in major depressive disorder reveals distinct abnormalities within the reward circuit

Abstract

Many neuroimaging studies have investigated reward processing dysfunction in major depressive disorder. These studies have led to the common idea that major depressive disorder is associated with blunted responses within the reward circuit, particularly in the ventral striatum. Yet, the link between major depressive disorder and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of major depressive disorder. To address this issue, we performed a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder and 803 healthy controls. Our findings argue against the common idea that major depressive disorder is primarily linked to deficits within the reward system. Instead, our results demonstrate that major depressive disorder is associated with opposing abnormalities in the reward circuit: hypo-responses in the ventral striatum and hyper-responses in the orbitofrontal cortex. The current findings suggest that dysregulated corticostriatal connectivity may underlie reward-processing abnormalities in major depressive disorder, providing an empirical foundation for a more refined understanding of abnormalities in the reward circuitry in major depressive disorder.

Fig. 1. Flowchart of study selection.

The systematic literature search identified a total of 41 neuroimaging studies that met the inclusion criteria, yielding 4 coordinate-based meta-analyses with at least 17 independent studies; ROI, region of interest; SVC, small volume correction; MDD, major depressive disorder

Fig. 2. Opposing abnormalities in the reward circuit in response to reward in major depressive disorder.

a To examine regions that consistently showed blunted response to reward, 22 studies reporting less activity in response to reward in people with major depressive disorder (MDD) than healthy controls (HC) were synthesized. Results indicated that these studies reliably report less activation in the ventral striatum (VS) in MDD. b To identify regions that consistently showed hyper-responses to reward, 18 studies reporting greater activity in response to reward in people with MDD than HC were meta-analyzed. Results indicated that these studies reliably report greater activation in the right orbitofrontal cortex (OFC) in MDD

Fig. 3. Hyper-responses to punishment in the sublenticular extended amygdala in major depressive disorder.

To conduct exploratory analyses to examine which brain regions consistently show elevated response to punishment in major depressive disorder (MDD) relative to healthy controls (HC), we meta-analyzed 24 studies reporting greater activity in response to punishment in people with MDD than HC. The results indicated that these studies reliably report greater activation in the left sublenticular extended amygdala (SLEA) in MDD