Objective-Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects.Method-Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses.Results-The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects.Conclusions-A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.Stressful life events are frequently associated with the onset of episodes of major depression (1, 2). Elevated levels of plasma cortisol (3, 4) and deficits in declarative memory mediated by the hippocampus (5-7) have also been reported in subgroups of patients with unipolar major depressive disorder. Preclinical studies have confirmed that chronic psychosocial stress and cortisol administration inhibit neurogenesis in the dentate gyrus (8-10) and cause atrophy or remodeling of the apical dendrites of the pyramidal neurons in the CA3 region of the hippocampus (reviewed in references 11-13). Morphometric techniques based on magnetic resonance imaging have been used to determine whether these preclinical findings of hippocampal damage can be extended to patients with major depression and other stress-related disorders. Over the last 5 years, several groups have confirmed smaller than normal volumes of the left hippocampus (14, 15) and of the left and right hippocampus (5, 16, 17) in unipolar major depressive disorder. A smaller hippocampal volume was correlated with the total duration of depression (5, 16). Other groups, however, have not found significant differences in hippocampal volume between patients with unipolar major depressiv...

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