Purpose: To investigate cerebral and cerebellar gray matter abnormalities in patients with first-episode major depressive disorder (MDD). Materials and methods: We examined the structural difference in regional gray matter density (GMD) between 22 first-episode MDD patients and 30 age-, gender- and education-matched healthy controls by optimized voxel-based morphometry (VBM) based on magnetic resonance imaging. Results: Compared with healthy controls, MDD patients showed decreased GMD in the right medial and left lateral orbitofrontal cortex, right dorsolateral prefrontal cortex (DLPFC), bilateral temporal pole, right superior temporal gyrus, bilateral anterior insular cortex, left parahippocampal gyrus, and left cerebellum. In addition, in MDD patients, there was a negative correlation between GMD values of the right DLPFC and the score of the depression rating scale. Conclusions: Our findings provided additional support for the involvement of limbic-cortical circuits in the pathophysiology of MDD and preliminary evidence that a defect involving the cerebellum may also be implicated. (C) 2010 Published by Elsevier Ireland Ltd.