Tuning the brain: Intrinsic resting-state connectomes distinguish major depressive disorder from social anxiety disorder in salience and limbic circuits

Background Major depressive disorder (MDD) and social anxiety disorder (SAD) are prevalent and frequently co-occurring. Few studies have directly compared MDD and SAD using spatially and frequency-resolved resting-state functional connectivity (rsFC). We examined whether rsFC networks show shared and diagnosis-associated features of MDD and SAD. Methods Baseline rsFC from 150 adults (MDD = 60; SAD = 55; healthy controls [HC] = 35) underwent group-information-guided ICA (GIG-ICA). Component spatial maps and frequency spectra were compared across groups with age, sex, and motion covariates. Follow-up regressions related ICA features to Hamilton Depression Rating Scale (HAM-D) and Liebowitz Social Anxiety Scale (LSAS). Robustness analyses evaluated motion, comorbidity, illness/treatment history, sex balance, and preprocessing choices. Results Relative to SAD, MDD showed reduced low-frequency rsFC in the salience network (SN; 0.045–0.058 Hz) and superior temporal gyrus (STG; 0.037–0.041, 0.054–0.093 Hz), whereas SAD showed greater fusiform/parahippocampal (FusPHG) spatial-map expression. FusPHG correlated positively with LSAS (β = 0.425, p < .001) and negatively with HAM-D (β = −0.375, p < .001). SN connectivity correlated negatively with HAM-D and LSAS, while STG connectivity correlated negatively with LSAS but not HAM-D. Parsimonious sensitivity models identified FusPHG spatial expression and STG 0.054–0.093 Hz power as the most stable candidate group-level associations; SN effects attenuated after fuller illness-course and lifetime-treatment proxy adjustment. Conclusions MDD and SAD showed candidate spatially and frequency-resolved network differences involving SN, STG, and FusPHG circuits. These preliminary findings indicate SAD and MDD differ in neural pathways linking salience-related control, social-auditory integration, and visual-affective simulation and require replication.