Structural and functional neuroimaging correlates of suicidal ideation in treatment-resistant major depressive disorder

ABSTRACT Background Treatment-resistant depression (TRD) is a severe form of major depressive disorder associated with elevated suicide risk. Identifying neurobiological correlates of suicidal ideation (SI), a key modifiable risk factor, has important clinical implications. This study examined structural and functional magnetic resonance imaging (MRI) correlates of SI severity in individuals with TRD. Methods Structural and resting-state functional MRI data were collected from 41 participants with TRD and a history of SI. Investigator-rated past-week depression and SI severity was evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Columbia Scale of Suicide Severity Rating Scale (C-SSRS), respectively. Cortical thickness and subcortical gray matter volumes were measured using FreeSurfer, and resting-state functional connectivity measures were determined using the CONN functional connectivity toolbox. Associations between SI severity and cortical thickness, subcortical gray matter volume, and resting-state functional connectivity were assessed. Results Whole-brain vertex-wise surface-based structural analyses revealed a significant negative correlation between right lateral occipital cortical thickness and past-week SI severity, covaried for age, sex and depression severity (p=0.03, cluster-corrected). Network-based statistics analyses among 58 preselected regions of interest revealed a significant association between SI severity and resting-state functional connectivity between the right posterior parietal cortex and the left anterior insula, bilateral temporooccipital middle temporal gyrus and left frontal orbital cortex (pFDR pFDR=0.017), covaried for depression severity. Post-hoc analyses further characterized effects, revealing negative associations between SI and functional connectivity measures (pFDR0.0001). Conclusions This multimodal imaging study identified distinct structural and functional correlates of SI severity in TRD. These findings highlight the need to further investigate neurobiological underpinnings of SI to better inform suicide risk assessments and intervention strategies in this high-risk population.