Temporoparietal structural-functional coupling abnormalities in drug-naïve youths with major depressive disorder and suicidal ideation

Major depressive disorder (MDD) in youth is associated with higher suicide risk. Although white matter and functional connectivity abnormalities have been reported in MDD patients with suicidal ideation (SI), how brain structure and function interact abnormally remains unclear. We conducted a cross-sectional study of participants aged 15–30, including 97 drug-naive MDD patients with SI, 44 without SI (nSI), and healthy controls (HC). We analyzed global and local structural-functional connectivity (SC-FC) coupling across groups and assessed its correlation with clinical features. The study revealed significant differences in SC-FC coupling among the three groups (SI, nSI, and HC). At the local level, differences were identified in the left superior temporal gyrus (STG.L) and left Heschl’s gyrus (HES.L). Specifically, the SI group exhibited the weakest negative SC-FC coupling in the HES.L compared to both the nSI group and HC group ( P FDR < 0.001). Additionally, a decrease in negative SC-FC coupling in the STG.L was observed in the SI group when compared to the HC group ( P FDR = 0.003). The HES.L SC-FC coupling alterations were negatively correlated with clinical symptoms of rumination and suicidal risk in the SI group. The findings suggest that MDD patients with SI exhibit disrupted SC-FC coupling, particularly in the HES.L and STG.L regions. These alterations were associated with higher levels of rumination and suicidal risk, underscoring the potential of SC-FC coupling as a candidate neurobiological correlate of suicidal ideation in MDD.