Major depressive disorder (MDD) is a severe and devastating condition. However, the anatomical basis behind the affective symptoms, cognitive symptoms, and somatic-vegetative symptoms of MDD is still unknown. To explore the mechanism behind the depressive symptoms in MDD, we used diffusion tensor imaging (DTI)–based structural brain connectivity analysis to investigate the network difference between MDD patients and healthy controls (CN), and to explore the association between network metrics and patients’ clinical symptoms. Twenty-six patients with MDD and 25 CN were included. A baseline 24-item Hamilton rating scale for depression (HAMD-24) score ≥ 21 and seven factors (anxiety/somatization, weight loss, cognitive disturbance, diurnal variation, retardation, sleep disturbance, hopelessness) scores were assessed. When compared with healthy subjects, significantly higher characteristic path length and clustering coefficient as well as significantly lower network efficiencies were observed in patients with MDD. Furthermore, MDD patients demonstrated significantly lower nodal degree and nodal efficiency in multiple brain regions including superior frontal gyrus (SFG), supplementary motor area (SMA), calcarine fissure, middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). We also found that the characteristic path length of MDD patients was associated with weight loss. Moreover, significantly lower global efficiency of MDD patients was correlated with higher total HAMD score, anxiety somatization, and cognitive disturbance. The nodal degree in SFG was also found to be negatively associated with disease duration. In conclusion, our results demonstrated that MDD patients had impaired structural network features compared to CN, and disruption of optimal network architecture might be the mechanism behind the depressive symptoms and emotion disturbance in MDD patients.

Background Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Further classification may help characterize its heterogeneity. We previously have shown differential metabolomic profiles of traditional Chinese medicine (TCM) diagnostic subtypes of MDD. We further determined brain connectomic associations with TCM subtypes of MDD. Methods In this naturalistic study, 44 medication-free patients with a recurrent depressive episode were classified into liver qi stagnation (LQS, n = 26) and Heart and Spleen Deficiency (HSD, n = 18) subtypes according to TCM diagnosis. Healthy subjects (n = 28) were included as controls. Whole-brain white matter connectivity was analyzed on diffusion tensor imaging. Results The LQS subtype showed significant differences in multiple network metrics of the angular gyrus, middle occipital gyrus, calcarine sulcus, and Heschl’s gyrus compared to the other two groups. The HSD subtype had markedly greater regional connectivity of the insula, parahippocampal gyrus, and posterior cingulate gyrus than the other two groups, and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole. The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity. Conclusions The LQS subtype is mainly characterized by aberrant connectivity of the audiovisual perception-related temporal-occipital network, whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbic-paralimbic network. Insular connectivity may serve a biomarker for TCM-based classification of depression. Trial registration Registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015 Electronic supplementary material The online version of this article (10.1186/s13020-019-0239-8) contains supplementary material, which is available to authorized users.