Apathy in melancholic depression and abnormal neural activity within the reward-related circuit

Major depressive disorder is a heterogeneous syndrome, of which the most common subtype is melancholic depression (MEL). Previous studies have indicated that anhedonia is frequently a cardinal feature in MEL. As a common syndrome of motivational deficit, anhedonia is closely associated with dysfunction in reward-related networks. However, little is currently known about apathy, another syndrome of motivational deficits, and the underlying neural mechanisms in MEL and non-melancholic depression (NMEL). Herein, the Apathy Evaluation Scale (AES) was used to compare apathy between MEL and NMEL. On the basis of resting-state functional magnetic resonance imaging, functional connectivity strength (FCS) and seed-based functional connectivity (FC) were calculated within reward-related networks and compared among 43 patients with MEL, 30 patients with NMEL, and 35 healthy controls. Patients with MEL had higher AES scores than those with NMEL (t = -2.20, P = 0.03). Relative to NMEL, MEL was associated with greater FCS (t = 4.27, P < 0.001) in the left ventral striatum (VS), and greater FC of the VS with the ventral medial prefrontal cortex (t = 5.03, P < 0.001) and dorsolateral prefrontal cortex (t = 3.18, P = 0.005). Taken together the results indicate that reward-related networks may play diverse pathophysiological roles in MEL and NMEL, thus providing potential directions for future interventions in the treatment of various depression subtypes.