Suicidal ideation (SI) in major depressive disorder (MDD) presents a serious clinical concern, yet its underlying biological mechanisms remain poorly understood. Using an exploratory, multimodal design, this study included 98 MDD patients with SI (MDDSI), 61 without SI (MDDₙSI), and 233 healthy controls (HC), and collected functional MRI and peripheral blood transcriptomic data. Network-based statistics of resting-state functional connectivity (FC) identified brain network differences among the three groups, followed by graph-theoretical analysis of derived hub regions. Differential module connectivity (MDC) analyses of blood transcriptomic modules were performed to identify group-level differences, and exploratory correlation analyses were performed to examine associations between brain network topology and transcriptomic alterations. A functional network centered on the caudal temporal thalamus (cTtha) showed significant group differences (MDDSI > MDDₙSI >HC; p < 0. 001), with increased nodal efficiency of the left cTtha in both the MDDSI (p = 0. 043) and MDDₙSI (p < 0. 001) groups compared with the HC group. Modules differentiating MDDSI from MDDₙSI were enriched in antiviral immune responses and epigenetic regulation (darkred, MDC = 1. 508, p = 0. 04; yellow, MDC = 0. 93, p = 0. 01), while SI-specific alterations involved mitochondrial energy dysregulation and nSI-specific alterations involved vascular and translational pathways. Notably, one immune-related gene module was significantly correlated with left cTtha betweenness centrality (r = 0. 274, p = 0. 021), degree centrality (r = 0. 262, p = 0. 027), and nodal efficiency (r = 0. 235, p = 0. 048) in the MDDSI group. This study indicates that MDD and SI are associated with cTtha-centered functional network alterations and peripheral transcriptomic dysregulation, and that, within MDD, SI may show a potential link between cTtha-centered brain network disruption and immune transcriptomic dysregulation. These results should be interpreted cautiously given the exploratory design, binary SI assessment, and modest effect sizes.
Wang et al. (Wed,) studied this question.