Insular-associated causal network of structural covariance evaluating progressive gray matter changes in major depressive disorder

Morphometric studies demonstrated wide-ranging distribution of brain structural abnormalities in major depressive disorder (MDD).This study explored the progressive gray matter volume (GMV) changes pattern of structural network in 108 MDD patients throughout the illness duration by using voxel-based morphometric analysis.The causal structural covariance network method was applied to map the causal effects of GMV alterations between the original source of structural changes and other brain regions as the illness duration prolonged in MDD. This was carried out by utilizing the Granger causality analysis to T1-weighted data ranked based on the disease progression information.With greater illness duration, the GMV reduction was originated from the right insula and progressed to the frontal lobe, and then expanded to the occipital lobe, temporal lobe, dorsal striatum (putamen and caudate) and the cerebellum. Importantly, results revealed that the right insula was the prominent node projecting positive causal influences (i.e., GMV decrease) to frontal lobe, temporal lobe, postcentral gyrus, putamen, and precuneus. While opposite causal effects were detected from the right insula to the angular, parahippocampus, supramarginal gyrus and cerebellum.This work may provide further information and vital evidence showing that MDD is associated with progressive brain structural alterations.