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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

Aberrant connectivity within the default mode network in first-episode, treatment-naïve major depressive disorder.

BACKGROUND: Convergent studies have highlighted the dysfunction of default mode network (DMN) in major depressive disorder (MDD). The altered connectivity in posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) was especially found to be of interest in the resting state functional connectivity analysis. Recently, more attention has turned to the internal functional connectivity within the DMN. However, the internal connection patterns within the DMN remain unclear at the initial onset of MDD. METHODS: Resting-state fMRI was performed on 38 first-episode, treatment-naïve MDD patients along with 38 matched healthy controls. Seed-based analysis was used to define the DMN and then a region-to-region connectivity analysis was performed to inspect the functional connectivity within the DMN. Spearman׳s rank correlation analysis was performed between significantly abnormal connectivities in MDD patients and clinical measurements. RESULTS: Decreased region-to-region connectivities within DMN were found between the PCC and dorsal medial prefrontal cortex (dmPFC), between PCC and the right inferior parietal gyrus/angular, as well as between the left thalamus and cerebellar tonsil. No significant increase in connectivity was found. Moreover, functional connectivity between the left thalamus and cerebellar tonsil revealed a marginal significant negative correlation with clinical Hamilton Depression Rating Scale (HDRS) scores. LIMITATIONS: Noteworthiness in morbidity, a high risk of mortality, and a high rate of medical service utilization of MDD make the current results uncertain to apply to the more complicated situations. CONCLUSIONS: Each region within DMN may have a specific, individual functional role. The reason to identify the pathological mechanism of MDD may not lie in the abnormal DMN functional connectivity, but rather in the abnormal functional connectivity within DMN.