Hippocampus-driving progressive structural alterations in medication-naïve major depressive disorder

Major depressive disorder (MDD) is associated with abnormalities in brain structure. However, structural abnormality findings have been inconsistent and how structural changes lead to progressive morphometric alterations in depressed brain regions remains unclear.

High-resolution T1-weighted magnetic resonance images of first-episode medication-naïve MDD patients (20 men, 36 women) and healthy control participants (33 men, 23 women) were evaluated. Voxel-based morphometry analysis was conducted based on T1-weighted images. The causal network of structural covariance analysis (CaSCN) was accomplished by applying Granger causality analysis to the sequenced T1-weighted images in order to assess causal effect of structural changes.

When comparing MDD patients and healthy controls, gray matter was greater in the bilateral amygdala, the bilateral hippocampus, the left parahippocampus, and the right fusiform, while it was lessened in the bilateral brainstem, the bilateral pallidum, and the bilateral thalamus. Selecting the hippocampus as the seed region to run further CaSCN analysis revealed that the hippocampus is a prominent node that exerts a causal effect on the amygdala and regions of the default mode network.

Our sample size was small and the subjects groups' ages were not well matched. We also recognize that the hippocampus is not necessarily the original source of brain network alteration in MDD.

The CaSCN clarified the causal relationship between progressive gray matter alterations in the hippocampus and in other regions. Our work provided evidence of a network spread mechanism in terms of the causal influence of hippocampal alteration on progressive brain structural alterations in MDD.