Alterations in local neural activity and functional connectivity density in first-episode and recurrent major depressive disorder: a resting-state fMRI study

Recurrent major depressive disorder (RMDD) is typically associated with more severe symptoms and poorer prognosis compared to first-episode major depressive disorder (FMDD). However, the specific neuropathological differences between these two stages remain unclear. This study aimed to characterize and compare the abnormal intrinsic brain activity patterns in FMDD and RMDD patients to elucidate the mechanisms underlying the recurrence and progression of depression. This study included a total of 99 participants, consisting of 33 FMDD patients, 20 RMDD patients, and 46 healthy controls (HCs). All participants underwent resting-state functional magnetic resonance imaging scans. Resting-state data were preprocessed and analyzed using DPABI to compute four-dimensional spatial-temporal consistency of local neural activity (FOCA) and functional connectivity density (FCD) metrics. Between-group differences were assessed with an analysis of covariance (ANCOVA) (covarying for age, sex and mean framewise displacement), followed by region-of-interest extraction and correlation analyses with clinical measures. Compared to HCs, both FMDD and RMDD groups showed reduced FOCA in the left superior parietal gyrus (SPG). Notably, the RMDD group exhibited significantly increased FOCA in the right inferior frontal gyrus (IFG), as well as elevated global and local FCD in the left anterior cingulate cortex (ACC) and right parahippocampal gyrus, compared to both FMDD and HCs. Furthermore, the aberrant FCD values in the left ACC were positively correlated with the number of depressive episodes and the Snaith-Hamilton Pleasure Scale (SHAPS) scores. The findings indicated distinct functional alterations in FMDD and RMDD, with enhanced functional connectivity of the left ACC potentially representing a key feature of functional dysregulation in RMDD.