Although progress has been made in exploring postpartum depression (PPD), the involvement of cerebral structure connectivity in PPD patients keeps unclear. To explore structural connectivity alternations in mothers with PPD, diffusion tensor imaging (DTI) and automated fiber quantification (AFQ) were used to calculate brain white matter microstructure properties. Cross-sectional. A total of 51 women with first-episode, treatment-näive PPD, and 49 matched healthy postpartum women (HPW) controls. A 3.0 T; single-shot echo-planar imaging sequence. DTI measurements of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were obtained for 18 specific white matter tracts. The relationship between PDD symptoms, hormone levels, and postpartum days was also investigated. Two sample t test and Pearson's correlation analysis. The analysis was performed by using a permutation-based multiple-comparison correction approach, with the threshold of P < 0.05 (family wise error corrected [FWE-corrected]) separately across the four different outcome measures. Women with PPD showed significantly increased FA and AD in right anterior thalamic radiation (ATR) tract and significantly increased FA and significantly reduced RD in the cingulum tract, compared to women without PPD. The RD values of right cingulum were significantly positively correlated with postpartum days in HPW (r=0.39). There were no significant relationships between brain measures and hormone levels in either patients or controls. DTI measures have revealed altered integrity in the white matter of the cortical-thalamic circuits in women with PPD compared to HPW. Damage to these circuits may be a structural basis for the impaired emotional regulation and blunted mother-infant bonding in mothers with PPD and a potential target for the development of new treatments. 2 TECHNICAL EFFICACY: Stage 3.