Melancholic depression (MD) is one of the most prevalent and severe subtypes of major depressive disorder (MDD). Previous studies have revealed inconsistent results regarding alterations in grey matter volume (GMV) of the hippocampus and amygdala of MD patients, possibly due to overlooking the complexity of their internal structure. The hippocampus and amygdala consist of multiple and functionally distinct subregions, and these subregions may play different roles in MD. This study aims to investigate the volumetric alterations of each subregion of the hippocampus and amygdala in patients with MD and non-melancholic depression (NMD).A total of 146 drug-naïve, first-episode MDD patients (72 with MD and 74 with NMD) and 81 gender-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent magnetic resonance imaging (MRI) scans. The subregional segmentation of hippocampus and amygdala was performed using the FreeSurfer 6.0 software. The multivariate analysis of covariance (MANCOVA) was used to detect GMV differences of the hippocampal and amygdala subregions between three groups. Partial correlation analysis was conducted to explore the relationship between hippocampus or amygdala subfields and clinical characteristics in the MD group. Age, gender, years of education and intracranial volume (ICV) were included as covariates in both MANCOVA and partial correlation analyses.Patients with MD exhibited a significantly lower GMV of the right hippocampal tail compared to HCs, which was uncorrelated with clinical characteristics of MD. No significant differences were observed among the three groups in overall and subregional GMV of amygdala.Our findings suggest that specific hippocampal subregions in MD patients are more susceptible to volumetric alterations than the entire hippocampus. The reduced right hippocampal tail may underlie the unique neuropathology of MD. Future longitudinal studies are required to better investigate the associations between reduced right hippocampal tail and the onset and progression of MD.© 2024. The Author(s).