Prefrontal impairments have been hypothesized to be most strongly associated with the cognitive and emotional dysfunction in depression. Recently, white matter microstructural abnormalities in prefrontal lobe have been reported in elderly patients with major depressive disorder (MDD) using diffusion tensor imaging (DTI). However, it is still unclear whether the same changes exist in younger patients. In the present study, we first utilized DTI to detect prefrontal white matter in young adults with MDD. Nineteen first-episode, untreated young adults with MDD and twenty age- and gender-matched healthy controls were recruited. DTI and localizing anatomic data were acquired. Then, the regions of interest (ROIs) were located in prefrontal white matter at 4 mm inferior, and 0, 4, 8, 12, 16 and 20 mm superior to the anterior commissure-posterior commissure (AC-PC) plane, respectively. Compared with healthy controls, patients with MDD showed significantly lower fractional anisotropy (FA) values in prefrontal white matter at bilateral 20 mm, right 16 mm and right 12 mm above the AC-PC. Furthermore, there was no significant correlation between the FA value of any ROI and illness course as well as severity of depression. Together with previous findings, the present results suggest that microstructural abnormalities in prefrontal white matter may occur early in the course of MDD and may be related to the neuropathology of depression throughout adulthood from young to elderly.