Subregional amygdala functional connectivity abnormalities and anhedonia impairments in first-episode schizophrenia

Background: Although abnormal amygdala functional connectivity (FC) has been reported in schizophrenia, most studies have treated the amygdala as a single structure. This study aimed to explore the association between amygdala subregional FC and anhedonia in patients with first-episode schizophrenia (FES). Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 FES patients (including 11 drug-naïve) and 33 matched healthy controls (HCs). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and anhedonia was evaluated via the Snaith-Hamilton Pleasure Scale (SHAPS). Whole-brain FC analyses of amygdala subregions were performed, followed by group comparisons and correlation analyses with clinical measures. Result: Compared to HCs, FES patients showed significantly reduced FC between specific amygdala subregions and cortical regions, particularly within the frontal, temporal, parietal, and limbic lobes ( P < 0.05, GRF correction). Anhedonia severity was positively correlated with altered FC in the centromedial (CM) subregion of the amygdala (AMY_CM), especially with the supplementary motor area (SMA) and paracentral lobule (PLG). Notably, the association between right AMY_CM–right SMA FC and anhedonia remained significant after adjusting for clinical symptom severity (r = 0.46, P = 0.02). Conclusions: FES patients exhibit disrupted FC between amygdala subregions and cortical areas, with specific patterns linked to anhedonia. These findings suggest that anhedonia may serve as a potential neurobiological marker independent of general clinical symptoms and highlight the role of amygdala–cortical dysconnectivity in the early pathophysiology of schizophrenia. Trial Registration: Data used for this analysis came from case-control studies. Clinical trial number: not applicable. (April 2018through March 2021).