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Alterations of core structural network connectome associated with suicidal ideation in major depressive disorder patients.

ABSTRACT: Suicide ideation (SI) is a most high-risk clinical sign for major depressive disorder (MDD). However, whether the rich-club network organization as a core structural network is associated with SI and how the related neural circuits are distributed in MDD patients remain unknown. Total 177 participants including 69 MDD patients with SI (MDDSI), 58 MDD without SI (MDDNSI) and 50 cognitively normal (CN) subjects were recruited and completed neuropsychological tests and diffusion-tensor imaging scan. The rich-club organization was identified and the global and regional topological properties of structural networks, together with the brain connectivity of specific neural circuit architectures, were analyzed. Further, the support vector machine (SVM) learning was applied in classifying MDDSI or MDDNSI from CN subjects. MDDSI and MDDNSI patients both exhibited disrupted rich-club organizations. However, MDDSI patients showed that the differential network was concentrated on the non-core low-level network and significantly destroyed betweeness centrality was primarily located in the regional non-hub regions relative to MDDNSI patients. The differential structural network connections involved the superior longitudinal fasciculus and the corpus callosum were incorporated in the cognitive control circuit and default mode network. Finally, the feeder serves as a potentially powerful indicator for distinguishing MDDSI patients from MDDNSI or CN subjects. The altered rich-club organization provides new clues to understand the underlying pathogenesis of MDD patients, and the feeder was useful as a diagnostic neuroimaging biomarker for differentiating MDD patients with or without SI.

SUBMITTER: Liu X

PROVIDER: S-EPMC8068724 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks.MethodsCognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength.ResultsAll cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course.ConclusionsOur study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.

Project description:Suicide is one of the leading causes of mortality worldwide. Various factors could lead to suicidal ideation (SI), while depression is the predominant cause among all mental disorders. Studies have shown that alterations in brain structures and networks may be highly associated with suicidality. This study investigated both neurological structural variations and network alterations in depressed patients with suicidal ideation by using generalized q-sampling imaging (GQI) and Graph Theoretical Analysis (GTA). This study recruited 155 participants and divided them into three groups: 44 depressed patients with suicidal ideation (SI+; 20 males and 24 females with mean age = 42, SD = 12), 56 depressed patients without suicidal ideation (Depressed; 24 males and 32 females with mean age = 45, SD = 11) and 55 healthy controls (HC; nine males and 46 females with mean age = 39, SD = 11). Both the generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values were evaluated in a voxel-based statistical analysis by GQI. We analyzed different topological parameters in the graph theoretical analysis and the subnetwork interconnections in the Network-based Statistical (NBS) analysis. In the voxel-based statistical analysis, both the GFA and NQA values in the SI+ group were generally lower than those in the Depressed and HC groups in the corpus callosum and cingulate gyrus. Furthermore, we found that the SI+ group demonstrated higher global integration and lower local segregation among the three groups of participants. In the network-based statistical analysis, we discovered that the SI+ group had stronger connections of subnetworks in the frontal lobe than the HC group. We found significant structural differences in depressed patients with suicidal ideation compared to depressed patients without suicidal ideation and healthy controls and we also found several network alterations among these groups of participants, which indicated that white matter integrity and network alterations are associated with patients with depression as well as suicidal ideation.

Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

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Alterations of core structural network connectome associated with suicidal ideation in major depressive disorder patients.

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