Anhedonia and dysregulation of an angular gyrus-centred and dynamic functional network in adolescent-onset depression

Anhedonia is an important aspect of adolescent-onset major depressive disorder (MDD) and is associated with increased risk of suicidal behaviors and poor treatment outcomes. However, the neural circuitry underlying this deficit has not been well defined. This study aims to identify the relationships between anhedonia and changes in static and dynamic functional connectivity (FC) in adolescent-onset MDD patients compared with healthy control subjects (HCs) and adult-onset MDD patients.A total of 157 participants completed the Snaith-Hamilton Pleasure Scale (SHAPS) to assess hedonic capacity. Resting-state functional imaging scans were analysed using graph theoretical analysis, network-based statistics (NBS) and sliding window correlation analysis to explore the potential patterns of neural network brain disruptions in adolescent-onset MDD. Pearson correlations and support vector machines regression (SVR) were used to explore correlations and predict network measures with SHAPS scores.Compared with those with adult-onset MDD, adolescent-onset MDD patients showed decreased FC in 7 nodes and 6 connections, with the right angular gyrus (AG), left AG and left paracentral lobule having the largest number of connected edges (P = 0.0396, NBS-corrected). Their average FC and SHAPS scores were positively correlated (r = 0.309, P = 0.035). Regarding dynamic FC, compared with HCs, adolescent-onset MDD patients showed a tendency towards a decreased frequency in moderate-intensity brain FC states (P = 0.014), which was significantly and positively correlated with SHAPS scores (r = 0.425, P = 0.003). SVR also revealed AG-centred FC and dynamic FC could predict SHAPS scores (MSE = 27.233, P = 0.001).These findings provide distinct evidence on the physiological mechanisms of adolescent-onset MDD and anhedonia.