Altered Functional Connectivity and Small-World Network Properties in MDD With Daytime Sleepiness: Implications for Anhedonia.

Background: Approximately 37.4% to 57.1% of people with major depressive disorder (MDD) exhibit symptoms of daytime sleepiness (DS). Patients with MDD with concurrent DS tend to have worse clinical outcomes and often experience severe anhedonia. As a key symptom of MDD, anhedonia is strongly associated with its severity. The aim of this study was to clarify the neuroimaging mechanisms of DS symptoms in MDD patients with anhedonia. Methods: A total of 22 patients were recruited into the DS group (Epworth Sleepiness Scale [ESS] score ≥ 7), and 45 patients were included in the no DS group (No DS) in this cross-sectional study. All subjects underwent resting state functional MRI, polysomnography (PSG) and clinical scale assessments. Anhedonia is assessed using the Revised Social Anhedonia Scale (RSAS), Revised Physical Anhedonia Scale (RPAS), and Temporal Experience of Pleasure Scale (TEPS). Employing the Dosenbach 160-node atlas, we obtained whole-brain functional networks and extracted topological features (global efficiency [Eglob], local efficiency [Eloc], path length [Lp], and clustering coefficient [Cp]) using a graph-theoretic approach. Group comparisons, covariate-adjusted regression analyses, and mediation analysis were performed to examine the association between ESS, anhedonia, and ventrolateral prefrontal cortex (vlPFC)-posterior cingulate cortex (PCC) functional connectivity (FC). Results: The two groups were comparable for demographic and clinical characteristics, with no differences in Hamilton Depression Rating Scale (HAMD) or Hamilton Anxiety Rating Scale (HAMA) scores or polysomnographic parameters. The DS group scored higher on the RPAS, while social and temporal anhedonia did not differ between groups. After adjusting for relevant clinical and medication covariates, continuous ESS scores remained independently associated with RPAS. In terms of brain networks, the DS group showed reduced FC between the default mode network (DMN) and frontoparietal network (FPN)-primarily linking the vlPFC with the PCC and precuneus-as well as within and between posterior parieto-occipital and visual networks (VNs). The DS group also exhibited extensive reductions in Eglob, Eloc, and Cp, with prolonged Lp. Mediation analysis revealed that vlPFC-PCC FC significantly mediated the association between ESS and RPAS. Conclusion: MDD patients with DS exhibit more severe physical anhedonia, which may be associated with reduced indicators of their extensive whole-brain networks and reduced FC between some functional brain networks. Our study may provide a neuroimaging mechanistic basis for clinical identification and intervention of anhedonia in MDD patients with DS.