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Abstract Background 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). Methods 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. Results 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. Conclusions 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.

BackgroundThe efficacy and prognosis of major depressive disorder (MDD) are limited by its heterogeneity. MDD with melancholic features is an important subtype of MDD. The present study aimed to reveal the white matter (WM) network changes in melancholic depression.Materials and MethodsTwenty-three first-onset, untreated melancholic MDD, 59 non-melancholic MDD patients and 63 health controls underwent diffusion tensor imaging (DTI) scans. WM network analysis based on graph theory and support vector machine (SVM) were used for image data analysis.ResultsCompared with HC, small-worldness was reduced and abnormal node attributes were in the right orbital inferior frontal gyrus, left orbital superior frontal gyrus, right caudate nucleus, right orbital superior frontal gyrus, right orbital middle frontal gyrus, left rectus gyrus, and left median cingulate and paracingulate gyrus of MDD patients. Compared with non-melancholic MDD, small-worldness was reduced and abnormal node attributes were in right orbital inferior frontal gyrus, left orbital superior frontal gyrus and right caudate nucleus of melancholic MDD. For correlation analysis, the 7th item score of the HRSD-17 (work and interest) was positively associated with increased node betweenness centrality (aBC) values in right orbital inferior frontal gyrus, while negatively associated with the decreased aBC in left orbital superior frontal gyrus. SVM analysis results showed that abnormal aBC in right orbital inferior frontal gyrus and left orbital superior frontal gyrus showed the highest accuracy of 81.0% (69/83), the sensitivity of 66.3%, and specificity of 85.2% for discriminating MDD patients with or without melancholic features.ConclusionThere is a significant difference in WM network changes between MDD patients with and without melancholic features.