Bergamino, MaurizioPasternak, OferFarmer, MadisonShenton, MarthaPaul Hamilton, J.2016-04-012015Bergamino, Maurizio, Ofer Pasternak, Madison Farmer, Martha E. Shenton, and J. Paul Hamilton. 2015. “Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression.” NeuroImage : Clinical 10 (1): 336-342. doi:10.1016/j.nicl.2015.11.020. http://dx.doi.org/10.1016/j.nicl.2015.11.020.2213-1582http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318670Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations of MDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior fronto-occipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD.en-USDiffusion tensor imagingFree-water corrected DTIMajor depressive disorderTract-based spatial statisticsFractional anisotropyAxial diffusivityJournal Article2016-04-0110.1016/j.nicl.2015.11.020