Reward dysfunction in major depression: multimodal neuroimaging evidence for refining the melancholic phenotype

Reward dysfunction is thought to play a core role in the pathophysiology of major depressive disorder (MDD). Event-related potential (ERP) and functional magnetic resonance imaging (fMRI) studies have identified reward processing deficits in MDD, but these methods have yet to be applied together in a single MDD sample. We utilized multimodal neuroimaging evidence to examine reward dysfunction in MDD. Further, we explored how neurobiological reward dysfunction would map onto subtypes of MDD. The feedback negativity (FN), an ERP index of reward evaluation, was recorded in 34 unmedicated depressed individuals and 42 never-depressed controls during a laboratory gambling task. Ventral striatal (VS) activation to reward was recorded in a separate fMRI session, using an identical task, among a subgroup of 24 depressed individuals and a comparison group of 18 non-depressed controls. FN amplitude was blunted in MDD. This effect was driven by a MDD subgroup characterized by impaired mood reactivity to positive events, a core feature of melancholic MDD. A similar pattern was observed for VS activation, which was also blunted among the MDD subgroup with impaired mood reactivity. Neither FN amplitude nor VS activation was related to the full, DSM-defined melancholic or atypical MDD subtypes. Across the MDD sample, FN amplitude and VS activation were correlated, indicating convergence across methods. These results indicate that not all MDD is characterized by reward dysfunction, and that there is meaningful heterogeneity in reward processing within MDD. The current study offers neurobiological evidence that impaired mood reactivity is a key phenotypic distinction for subtyping MDD, and further suggests that the existing melancholic phenotype may require further refinement.