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OBJECTIVE: The authors investigated the relationship between depression duration and cerebral gray matter volume in female patients with recurrent major depressive disorder. METHOD: Magnetic resonance imaging was used to measure intracranial and total brain volumes as well as gray matter and white matter volumes of the cerebrum; frontal, temporal, parietal, and occipital lobes; cerebellum; and the lateral and third ventricles in 23 female patients with DSM-IV major depression. RESULTS: Correlation and regression analyses showed a significant relationship between total illness duration and cerebral gray matter (including cortical lobe) volume after correction for intracranial volume and age. CONCLUSIONS: Depressive states may lead to changes in global cerebral gray matter volume.