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The Journal of Neuroscience, June 15, 1999, 19(12):5034-5043

Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression

Yvette I. Sheline1, 2, 3, Milan Sanghavi1, Mark A. Mintun1, 2, 3, and Mokhtar H. Gado2, 3

Departments of 1 Psychiatry and 2 Radiology 2 and the 3 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Key words: hippocampus; depression; age; amygdala; magnetic resonance imaging; MRI; glucocorticoids; neurotoxicity; stereology

Copyright © 1999 Society for Neuroscience  0270-6474/99/19125034-10$05.00/0


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 Am. J. PsychiatryHome page
J. K. Belanoff, M. Kalehzan, B. Sund, S. K. Fleming Ficek, and A. F. Schatzberg
Cortisol Activity and Cognitive Changes in Psychotic Major Depression
Am J Psychiatry, October 1, 2001; 158(10): 1612 - 1616.
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 Am. J. Pathol.Home page
P. J. Lucassen, M. B. Muller, F. Holsboer, J. Bauer, A. Holtrop, J. Wouda, W. J. G. Hoogendijk, E. R. De Kloet, and D. F. Swaab
Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure
Am. J. Pathol., February 1, 2001; 158(2): 453 - 468.
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 Arch Gen PsychiatryHome page
M. Driessen, J. Herrmann, K. Stahl, M. Zwaan, S. Meier, A. Hill, M. Osterheider, and D. Petersen
Magnetic Resonance Imaging Volumes of the Hippocampus and the Amygdala in Women With Borderline Personality Disorder and Early Traumatization
Arch Gen Psychiatry, December 1, 2000; 57(12): 1115 - 1122.
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 J. Neurosci.Home page
D. M. Lyons, J. M. Lopez, C. Yang, and A. F. Schatzberg
Stress-Level Cortisol Treatment Impairs Inhibitory Control of Behavior in Monkeys
J. Neurosci., October 15, 2000; 20(20): 7816 - 7821.
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 Arch Gen PsychiatryHome page
R. M. Sapolsky
Glucocorticoids and Hippocampal Atrophy in Neuropsychiatric Disorders
Arch Gen Psychiatry, October 1, 2000; 57(10): 925 - 935.
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 Arch Gen PsychiatryHome page
G. Ende, D. F. Braus, S. Walter, W. Weber-Fahr, and F. A. Henn
The Hippocampus in Patients Treated With Electroconvulsive Therapy: A Proton Magnetic Resonance Spectroscopic Imaging Study
Arch Gen Psychiatry, October 1, 2000; 57(10): 937 - 943.
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 Br. J. PsychiatryHome page
D. FANNON, L. TENNAKOON, S. O'CEALLAIGH, V. DOKU, W. SONI, X. CHITNIS, J. LOWE, A. SUMICH, and T. SHARMA
Third ventricle enlargement and developmental delay in first-episode psychosis: preliminary findings
The British Journal of Psychiatry, October 1, 2000; 177(4): 354 - 359.
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 Am. J. PsychiatryHome page
M. D. De Bellis, D. B. Clark, S. R. Beers, P. H. Soloff, A. M. Boring, J. Hall, A. Kersh, and M. S. Keshavan
Hippocampal Volume in Adolescent-Onset Alcohol Use Disorders
Am J Psychiatry, May 1, 2000; 157(5): 737 - 744.
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 JWatch PsychiatryHome page
Hippocampal Loss Associated with Lifetime Duration of Depression
Journal Watch Psychiatry, September 1, 1999; 1999(901): 6 - 6.
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