Association of executive function with suicidality based on resting-state functional connectivity in young adults with subthreshold depression

Abstract

Subthreshold depression (StD) is associated an increased risk of developing major depressive disorder (MDD) and suicidality. Suicidality could be linked to distress intolerance and use of context-dependent strategies. We identified neural correlates of executive functioning among the hubs in the resting-state functional connectome (rs-FCN) and examined associations with recent suicidality in StD and MDD. In total, 79 young adults [27 StD, 30 MDD, and 23 healthy controls (HC)] were scanned using magnetic resonance imaging. Neurocognitive measures of the mean latency to correct five moves in the One Touch Stockings of Cambridge (OTSMLC5), spatial working memory between errors (SWMBE), rapid visual information processing A′ (RVPA′), and the stop signal reaction time in the stop signal test (SSTSSRT) were obtained. Global graph metrics were calculated to measure the network integration, segregation, and their balance in the rs-FCN. Regional graph metrics reflecting the number of neighbors (degree centrality; DC), participation in the shortcuts (betweenness centrality; BC), and accessibility to intersections (eigenvector centrality; EC) in the rs-FCN defined group-level hubs for StD, HC, and MDD, separately. Global network metrics were comparable among the groups (all P > 0.05). Among the group-level hubs, regional graph metrics of left dorsal anterior insula (dAI), right dorsomedial prefrontal cortex (dmPFC), right rostral temporal thalamus, right precuneus, and left postcentral/middle temporal/anterior subgenual cingulate cortices were different among the groups. Further, significant associations with neurocognitive measures were found in the right dmPFC with SWMBE, and left dAI with SSTSSRT and RVPA′. Shorter OTSMLC5 was related to the lower centralities of right thalamus and suffer of recent 1-year suicidal ideation (all Ps < 0.05 in ≥ 2 centralities out of DC, BC, and EC). Collectively, salience and thalamic networks underlie spatial strategy and planning, response inhibition, and suicidality in StD and MDD. Anti-suicidal therapies targeting executive function and modulation of salience-thalamic network in StD and MDD are required.