Uncovering Shared and Distinct Brain Connectome Dynamics in Working Memory Tasks Between Bipolar and Unipolar Depression

OBJECTIVES: Differences in working memory (WM) may serve to distinguish bipolar disorder depression (BDD) from major depressive disorder (MDD). This work aims to utilize degree centrality (DC), a metric of graph theory, to explore whole-brain dynamic functional connectivity alterations related to WM in the two disorders. METHODS: We calculated the coefficient variation of dynamic DC (CVDC) and utilized clustering analysis to identify persistent meta-stable states of DC configuration in BDD, MDD, and healthy controls (HC) during n-back tasks. We further tested associations of the altered DC and clinical symptoms. Meanwhile, imaging transcriptomic analysis was used to explore the genetic mechanisms underlying the differences in DC between BDD and MDD. RESULTS: No significant difference was observed in CVDC among the three groups. In the meta-stable state 1 under the '2-back vs. 0-back' contrast, there showed a ladder-like pattern across BDD, MDD, and HC in bilateral parahippocampal gyri, left anterior cingulate cortex, left Heschl gyrus, right precentral gyrus, right precuneus, bilateral middle temporal gyrius, right inferior frontal gyrus, and right superior frontal gyrus. Significant DC differences between BDD and MDD in the right superior frontal gyrus and right middle temporal gyrus were primarily associated with gene enrichment in the chemical synaptic transmission, glutamatergic synapse, calcium ion binding, and pathways of neurodegeneration-multiple diseases pathway. CONCLUSION: BDD and MDD showed highly similar aberrant dynamic characteristics of brain functional connectivity when facing increased cognitive demands, but BDD showed a relatively greater magnitude than MDD.