ObjectivesPostpartum depression (PPD) is a severe postpartum psychiatric disorder with unclear pathogenesis. Previous neuroimaging studies have reported structural or functional alterations in areas associated with emotion regulation, cognitive disorder, and parenting behaviors of PPD. The primary goal of this investigation was to explore the presence of brain structural alterations and relevant functional changes in PPD patients.MethodsA total of 28 patients and 30 matched healthy postnatal women (HPW) underwent both three-dimensional T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Structural analysis was performed by voxel-based morphometry (VBM), followed by resting-state functional analysis using a seed-based whole-brain functional connectivity (FC) approach with abnormal gray matter volume (GMV) regions as seed.ResultsCompared with HPW, the PPD patients showed increased GMV in the left dorsolateral prefrontal cortex (DLPFC.L), the right precentral gyrus (PrCG.R), and the orbitofrontal cortex (OFC). In the PPD group, the DLPFC.L showed increased FC with the right anterior cingulate and paracingulate gyri (ACG.R) and the right middle frontal gyrus (MFG.R); the FC between the PrCG.R and the right median cingulate and paracingulate gyri (DCG.R) exhibited enhanced; the OFC showed increased FC with MFG.R and the left inferior occipital gyrus (IOG.L). In PPD, GMV of DLPFC.L was positively correlated with EDPS scores (r= 0.409p= 0.031), and FC of PrCG.R-DCG.R was positively correlated with EDPS scores (r= 0.483p= 0.020).ConclusionStructural and functional damage of the DLPFC.L and OFC is associated with cognitive disorders and parenting behaviors in PPD, while structural abnormalities of the DLPFC.L and PrCG.R are involved in impaired executive function. The increased GMV of DLPFC.L may be a unique structural pathological mechanism of PPD related to the inability of PPD patients to withstand long-term parenting stress. These findings have important implications for understanding neural mechanisms in PPD.