Cortical hierarchy disorganization in major depressive disorder and its association with suicidality.

Objectives: To explore the suicide risk-specific disruption of cortical hierarchy in major depressive disorder (MDD) patients with diverse suicide risks. Methods: Ninety-two MDD patients with diverse suicide risks and 38 matched controls underwent resting-state functional MRI. Connectome gradient analysis and stepwise functional connectivity (SFC) analysis were used to characterize the suicide risk-specific alterations of cortical hierarchy in MDD patients. Results: Relative to controls, patients with suicide attempts (SA) had a prominent compression from the sensorimotor system; patients with suicide ideations (SI) had a prominent compression from the higher-level systems; non-suicide patients had a compression from both the sensorimotor system and higher-level systems, although it was less prominent relative to SA and SI patients. SFC analysis further validated this depolarization phenomenon. Conclusion: This study revealed MDD patients had suicide risk-specific disruptions of cortical hierarchy, which advance our understanding of the neuromechanisms of suicidality in MDD patients.

Aberrant Inter-hemispheric Connectivity in Patients With Recurrent Major Depressive Disorder: A Multimodal MRI Study.

Objective: Inter-hemispheric network dysconnectivity has been well-documented in patients with recurrent major depressive disorder (MDD). However, it has remained unclear how structural networks between bilateral hemispheres relate to inter-hemispheric functional dysconnectivity and depression severity in MDD. Our study attempted to investigate the alterations in corpus callosum macrostructural and microstructural as well as inter-hemispheric homotopic functional connectivity (FC) in patients with recurrent MDD and to determine how these alterations are related with depressive severity. Materials and Methods: Resting-state functional MRI (fMRI), T1WI anatomical images and diffusion tensor MRI of the whole brain were performed in 140 MDD patients and 44 normal controls matched for age, sex, years of education. We analyzed the macrostructural and microstructural integrity as well as voxel-mirrored homotopic functional connectivity (VMHC) of corpus callosum (CC) and its five subregion. Two-sample t-test was used to investigate the differences between the two groups. Significant subregional metrics were correlated with depression severity by spearman's correlation analysis, respectively. Results: Compared with control subjects, MDD patients had significantly attenuated inter-hemispheric homotopic FC in the bilateral medial prefrontal cortex, and impaired anterior CC microstructural integrity (each comparison had a corrected P < 0.05), whereas CC macrostructural measurements remained stable. In addition, disruption of anterior CC microstructural integrity correlated with a reduction in FC in the bilateral medial prefrontal cortex, which correlated with depression severity in MDD patients. Furthermore, disruption of anterior CC integrity exerted an indirect influence on depression severity in MDD patients through an impairment of inter-hemispheric homotopic FC. Conclusion: These findings may help to advance our understanding of the neurobiological basis of depression by identifying region-specific interhemispheric dysconnectivity.

An aberrant hippocampal subregional network, rather than structure, characterizes major depressive disorder.

BACKGROUND: Behavioral and neuroimaging studies have implicated the hippocampus as a cardinal neural structure in major depressive disorder (MDD) pathogenesis. The hippocampal subregion-specific structural and functional abnormalities in MDD remain unknown. METHODS: Multimodal magnetic resonance imaging (MRI) was acquired in 140 patients with MDD and 44 age- and sex-matched healthy controls (HCs). We quantified hippocampal subregional volumes and fractional anisotropy (FA) following a structural and diffusion MRI data analysis processing stream. Hippocampal subregional networks were established using seed-based functional connectivity (FC) analysis. Univariate analysis was used to investigate the differences between the two groups. Significant subfield metrics were correlated with depression severity. RESULTS: Compared with HCs, we did not find significant differences in subregional volumes or FA metrics in the MDD group. The MDD group exhibited a significantly weaker connectivity of the right hippocampal subregional networks with the temporal cortex (extending to the insula) and basal ganglia but showed increased connectivity of the right subiculum to the bilateral lingual gyrus. The FC between the right cornu ammonis 1 and right fusiform, between the right hippocampal amygdala transition area and the bilateral basal ganglia, were negatively correlated with depression severity (r = -0.224, p = 0.010; r = -0.196, p = 0.025, respectively) in the MDD group. LIMITATIONS: This study did not consider the longitudinal changes in the structure and functional connectivity of the hippocampal subregion. CONCLUSION: These findings advance our understanding of the neurobiological basis of depression by identifying the hippocampal subregional structural and functional abnormalities.