Functional disconnectivity during the resting state has been observed in subjects with major depressive disorder (MDD), and in subjects at high genetic risk for major depression during task performance. It is hypothesized that functional impairments in certain brain areas are present in patients with MDD and in their first-degree relatives. To test this hypothesis, an analysis of regional homogeneity (ReHo) of the whole brain was performed on 45 subjects. Compared with the control group, subjects with MDD and those at high risk for MDD exhibited significantly decreased ReHo in the right insula and in the left cerebellum. These abnormalities may play an important role in the pathophysiology of depression.