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BackgroundFindings of brain structural changes in major depressive disorder are still inconsistent, partly because some crucial clinical variables have not been taken into account.AimsTo investigate the effect of major depressive disorder on grey matter volumes.MethodVoxel-based morphometry was used to compare 66 patients with depression at different illness stages (22 each with first-episode, remitted-recurrent and treatment resistant/chronic depression) with 32 healthy controls. Brain volumes were correlated with clinical variables.ResultsVoxel-based morphometry showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus (P<0.05, family wise error-corrected). Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial …