Altered neural activity in the reward-related circuit associated with anhedonia in mild to moderate Major Depressive Disorder

Background: Anhedonia is a significant predictor of disease progression and treatment outcomes in Major Depressive Disorder (MDD), linked to reward network dysfunctions. However, understanding of its underlying neural mechanisms remains limited. This study aimed to investigate the brain functional mechanisms underlying MDD with anhedonia using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: The Snaith-Hamilton Pleasure Scale (SHAPS) was used to evaluation MDD with anhedonia (anMDD) and non-anhedonia MDD (non-anMDD). Forty-eight patients with anMDD, Forty-four patients with non-anMDD, and Fifty healthy controls (HCs) were enrolled for the fMRI scans. A seed-based functional connectivity (FC) method was employed to explore reward network abnormalities. Results: anMDD patients exhibited lower FC values in Ventral Striatum (VS), right lateral Ventral Tegmental Area (VTA_R), left Thalamus (THA_L), and higher FC values in Ventromedial Prefrontal Cortex (vmPFC), left Anterior Insula (AI_L), and Presupplementary Motor Area (Pre-SMA) compared to HCs. Comparing anMDD to non-anMDD, significant differences were observed in FC values of VS, vmPFC, Pre-SMA, and THA_L regions. Cor-relation analysis revealed positive correlations between FC values of VS_R and NAc_R, as well as THA_L and Cerebellum_Crus1_L, with SHAPS scores. Negative correlations were observed between FC values of Pre-SMA and the right caudate, and between vmPFC and Frontal_Mid_Orb_L, and SHAPS scores. Conclusion: Both anMDD and non-anMDD groups demonstrated abnormal FCs in the reward network. These findings indicate distinct roles of reward-related circuits in the two subtypes, contributing to a refined under-standing of depression phenotypes and potential directions for targeted interventions.