Brain structural connectome comprise of a minority of efficiently interconnected rich club nodes that are regarded as ‘high-order regions’. The remission of major depressive disorder (MDD) in response to selective serotonin reuptake inhibitor (SSRI) treatment could be investigated by the hierarchical structural connectomes’ alterations of subnetworks.

Fifty-five MDD patients who achieved remission underwent diffusion tensors imaging (DTI) scanning from 3 cohorts before and after 8-weeks antidepressant treatment. Five hierarchical subnetworks namely, rich, local, feeder, rich-feeder and feeder-local, were constructed according to the different combinations of connections and nodes as defined by rich club architecture. The critical treatment-related subnetwork pattern was explored by multivariate pattern analysis with support vector machine to differ the pre-/post-treatment patients. Then, relationships between graph metrics of discriminative subnetworks/ nodes and clinical variables were further explored.

The feeder-local subnetwork presented the most discriminative power in differing pre-/post- treatment patients, while the rich-feeder subnetwork had the highest discriminative power when comparing pre-treatment patients and controls. Furthermore, based on the feeder connection, which indicates the information transmission between the core and non-core architectures of brain networks, its topological measures were found to be significantly correlated with the reduction rate of 17-item Hamilton Rating Scale for Depression.

Although pathological lesion on MDD relied on abnormal core organization, disease remission was association with the compensation from non-core organization. These results suggested that the dysfunctions arising from hierarchical subnetworks are compensated by increased information interactions between core brain regions and functionally diverse regions.