Understanding structural-functional connectivity coupling in patients with major depressive disorder: A white matter perspective

Purpose: To elucidate the structural-functional connectivity (SC-FC) coupling in white matter (WM) tracts in patients with major depressive disorder (MDD). Methods: A total of 178 individuals diagnosed with MDD and 173 healthy controls (HCs) were recruited for this study. The Euclidean distance was calculated to assess SC-FC coupling. The primary analyses focused on investigating alterations in SC-FC coupling in WM tracts of individuals with MDD. Additionally, we explored the association between coupling and clinical symptoms. Secondary analyses examined differences among three subgroups of MDD: those with suicidal ideation (SI), those with a history of suicidal attempts (SA), and those non-suicidal (NS). Results: The study revealed increased SC-FC coupling mainly in the middle cerebellar peduncle and bilateral corticospinal tract (P-FDR < 0.05) in patients with MDD compared with HCs. Additionally, right cerebral peduncle coupling strength exhibited a significant positive correlation with Hamilton Anxiety Scale scores (r = 0.269, P-FDR = 0.041), while right cingulum (hippocampus) coupling strength showed a significant negative correlation with Nurses' Global Assessment of Suicide Risk scores (r =-0.159, P-FDR = 0.036). An increase in left anterior limb of internal capsule (P-Bonferroni < 0.01) and left corticospinal tract (P-Bonferroni < 0.05) coupling has been observed in MDD with SI. Additionally, a decrease in right posterior limb of internal capsule coupling has been found in MDD with SA (P-Bonferroni < 0.05). Conclusions: This study emphasizes the variations in SC-FC coupling in WM tracts in individuals with MDD and its subgroups, highlighting the crucial role of WM networks in the pathophysiology of MDD.