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OBJECTIVE: A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. METHOD: A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. RESULTS: Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. CONCLUSIONS: Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.