Despite the extensive therapy options available for depression, treatment-resistant depression (TRD) occurs in 20-30% of depressed patients. . Consequently, identification of neural changes in TRD could support to better understand the mechanism of resistance and to improve the treatment of individual depressed patients. We aimed to investigate the white-matter microstructure in a sample of depressed patients in which response to treatment was subsequently evaluated 6 months after. Our findings suggest the abnormalities of the white-matter integrity in multiple white matter tracts, such as anterior limb of internal capsule and genu of corpus may play a role in the pathogenesis of treatment-resistant depression.