Abnormal connectivity of anterior-insular subdivisions and relationship with somatic symptom in depressive patients

Depressive patients frequently present with somatic complaints such as pain and fatigue. The anterior insula (AI) is a crucial region for somatic processing, but reported contributions of AI dysfunction to somatic symptoms have varied across studies. We speculated that functional heterogeneity among AI subdivisions may contribute to this inconsistency. To reveal the correlation between each subdivision and somatic symptoms, we investigated resting-state functional connectivity (RSFC) based on seeds within distinct AI subdivisions in 45 depressive patients and 35 matched healthy controls (HCs). Depressive and somatic symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and the 15-item somatic symptom severity scale of the Patient Health Questionnaire (PHQ-15), respectively. The contributions of AI subregion-specific pathways to depression were further validated by examining changes in symptom severity and RSFC following electroconvulsive therapy (ECT). At baseline, depressive patients exhibited weaker RSFC between ventral AI (vAI) and right orbitofrontal cortex (rOFC) than HCs. Moreover, vAI–rOFC RSFC strength was negatively correlated with PHQ-15 and HDRS scores, indicating that weaker RSFC predicted greater symptom severity. ECT reduced depressive and somatic symptoms, and symptom mitigation was correlated with enhanced vAI–rOFC RSFC. The findings suggest that reduced vAI–rOFC RSFC underlies the somatic symptoms of depression and that enhancing vAI–rOFC RSFC can contribute to amelioration of somatic symptoms.