Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

Abstract

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.

White matter microstructural abnormalities and their association with anticipatory anhedonia in depression

“…Additionally, alterations of WM microstructure have also been positively correlated with depression severity. Previous studies have repeatedly reported that WM microstructural abnormalities may play a role in the emergence of depression and suicidal ideations in patients with MDD (Jia et al, 2014;Myung et al, 2016). Our findings suggest that the forceps minor and the cingulum may play an important role in integrating motivational information leading to loss of pleasure experience and depression.…”

Aberrant intrinsic functional connectivity in thalamo‐cortical networks in major depressive disorder

“…MDD patients have been found to have increased mediodorsal thalamus but reduced dorsal PFC activity and reduced connectivity between the medial thalamic and the dorsal PFC at rest or in response to negative affective stimuli . Reduced thalamic‐PFC structural connectivity observed in MDD patients may provide an anatomical basis for the current findings . The weakened thalamus connectivity with the PFC may be associated with abnormal norepinephrine transmission, based on recent findings of elevated norepinephrine transporter availability in the mediodorsal thalamus and significant association with impaired attention in MDD .…”

“…Several issues need to be further addressed. Studies showing altered thalamo‐frontal structural connections may provide an anatomical basis for the current findings . However, strong functional connections commonly exist between regions with no direct structural connection, rendering the straightforward inference of functional connectivity from structural connectivity impractical .…”

“…8 Reduced thalamic-PFC structural connectivity observed in MDD patients may provide an anatomical basis for the current findings. 28,29 The In contrast to the prefrontal thalamus ROI, the motor and somatosensory thalamus subdivisions demonstrated connectivity strengthening with the PFC and/or posterior DMN regions in MDD patients. Besides the frequently studied thalamic-PFC connectivity, the thalamus was also strongly connected with sensorimotor regions.…”

“…Studies showing altered thalamo-frontal structural connections may provide an anatomical basis for the current findings. 28,29 However, strong functional connections commonly exist between regions with no direct structural connection, rendering the straightforward inference of functional connectivity from structural connectivity impractical. 52 Future studies using a multimodal imaging data will help to clarify the contributions of direct/indirect structural connections to thalamo-cortical functional connectivity in MDD.…”