Characteristics of Intrinsic Brain Functional Connectivity Alterations in Major Depressive Disorder Patients With Suicide Behavior

Abstract

Background: The intrinsic brain functional connectivity of suicide attempts in major depressive disorder (MDD) remains incompletely understood.

Purpose: To investigate graph-theoretical based functional connectivity strength (FCS) alterations in MDD patients with suicidal behavior.

Study type: Prospective.

Subjects: Fifty medication-free MDD patients, with (suicide attempters, SA, N = 15) and without (non-attempters, nSA, N = 35) a history of a suicide attempt, and 37 healthy controls (HC).

Field strength/sequence: Resting-state functional magnetic resonance imaging (fMRI) using a gradient-echo imaging sequence was acquired at 3.0 T.

Assessment: For each individual, voxel-wise whole-brain functional network was constructed and graph-theoretical based FCS map was calculated. For each individual in two patient groups, the seed-based functional connectivity map was constructed.

Statistical tests: Non-parameter permutation tests, analysis of covariance, two-sample t-test, Chi-square test, and Pearson correlation analysis. A P value <0.05 was considered statistically significant.

Results: Relative to the HC group, two MDD patient groups showed significantly lower FCS in the left hippocampus, while nSA patients showed additionally lower FCS in more widespread regions (P < 0.05). Importantly, comparing to nSA patients, SA patients had significantly higher FCS in the right orbitofrontal cortex (OFC) and bilateral dorsomedial prefrontal cortex (dmPFC) (P < 0.05). Further seed-based functional connectivity analysis revealed that the right OFC exhibited significantly higher connectivity to right middle frontal gyrus and lower connectivity to the left anterior cingulate cortex and left calcarine sulcus, and the bilateral dmPFC had significantly higher connectivity to the left middle frontal gyrus and right inferior temporal gyrus in the SA patients than in the nSA patients (P < 0.05).

Data conclusion: This study identified disconnections of the OFC and dmPFC which were putatively related to a higher risk of suicidal behavior in MDD patients, thus extended the understanding of suicidal behavior at a brain circuit level.

Level of evidence: 3 TECHNICAL EFFICACY STAGE: 3.

Keywords: connectomics; depression; graph theory; psychoradiology; resting-state fMRI; suicidality.