Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Apr 30;93(9):3908–3913. doi: 10.1073/pnas.93.9.3908

Hippocampal atrophy in recurrent major depression.

Y I Sheline 1, P W Wang 1, M H Gado 1, J G Csernansky 1, M W Vannier 1
PMCID: PMC39458  PMID: 8632988

Abstract

Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity.

Full text

PDF
3908

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboitiz F., Scheibel A. B., Zaidel E. Morphometry of the Sylvian fissure and the corpus callosum, with emphasis on sex differences. Brain. 1992 Oct;115(Pt 5):1521–1541. doi: 10.1093/brain/115.5.1521. [DOI] [PubMed] [Google Scholar]
  2. Andreasen N. C., Flashman L., Flaum M., Arndt S., Swayze V., 2nd, O'Leary D. S., Ehrhardt J. C., Yuh W. T. Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. JAMA. 1994 Dec 14;272(22):1763–1769. [PubMed] [Google Scholar]
  3. Armanini M. P., Hutchins C., Stein B. A., Sapolsky R. M. Glucocorticoid endangerment of hippocampal neurons is NMDA-receptor dependent. Brain Res. 1990 Nov 5;532(1-2):7–12. doi: 10.1016/0006-8993(90)91734-x. [DOI] [PubMed] [Google Scholar]
  4. Aronson S. M. Intracranial vascular lesions in patients with diabetes mellitus. J Neuropathol Exp Neurol. 1973 Apr;32(2):183–196. doi: 10.1097/00005072-197304000-00001. [DOI] [PubMed] [Google Scholar]
  5. Axelson D. A., Doraiswamy P. M., McDonald W. M., Boyko O. B., Tupler L. A., Patterson L. J., Nemeroff C. B., Ellinwood E. H., Jr, Krishnan K. R. Hypercortisolemia and hippocampal changes in depression. Psychiatry Res. 1993 May;47(2):163–173. doi: 10.1016/0165-1781(93)90046-j. [DOI] [PubMed] [Google Scholar]
  6. Bartzokis G., Mintz J., Marx P., Osborn D., Gutkind D., Chiang F., Phelan C. K., Marder S. R. Reliability of in vivo volume measures of hippocampus and other brain structures using MRI. Magn Reson Imaging. 1993;11(7):993–1006. doi: 10.1016/0730-725x(93)90218-3. [DOI] [PubMed] [Google Scholar]
  7. Berg L., Hughes C. P., Coben L. A., Danziger W. L., Martin R. L., Knesevich J. Mild senile dementia of Alzheimer type: research diagnostic criteria, recruitment, and description of a study population. J Neurol Neurosurg Psychiatry. 1982 Nov;45(11):962–968. doi: 10.1136/jnnp.45.11.962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bremner J. D., Randall P., Scott T. M., Bronen R. A., Seibyl J. P., Southwick S. M., Delaney R. C., McCarthy G., Charney D. S., Innis R. B. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995 Jul;152(7):973–981. doi: 10.1176/ajp.152.7.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carroll B. J., Feinberg M., Greden J. F., Tarika J., Albala A. A., Haskett R. F., James N. M., Kronfol Z., Lohr N., Steiner M. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry. 1981 Jan;38(1):15–22. doi: 10.1001/archpsyc.1981.01780260017001. [DOI] [PubMed] [Google Scholar]
  10. Cavazos J. E., Das I., Sutula T. P. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci. 1994 May;14(5 Pt 2):3106–3121. doi: 10.1523/JNEUROSCI.14-05-03106.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Charness M. E. Brain lesions in alcoholics. Alcohol Clin Exp Res. 1993 Feb;17(1):2–11. doi: 10.1111/j.1530-0277.1993.tb00718.x. [DOI] [PubMed] [Google Scholar]
  12. Coffey C. E., Wilkinson W. E., Weiner R. D., Parashos I. A., Djang W. T., Webb M. C., Figiel G. S., Spritzer C. E. Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch Gen Psychiatry. 1993 Jan;50(1):7–16. doi: 10.1001/archpsyc.1993.01820130009002. [DOI] [PubMed] [Google Scholar]
  13. Desmond D. W., Tatemichi T. K., Paik M., Stern Y. Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. Arch Neurol. 1993 Feb;50(2):162–166. doi: 10.1001/archneur.1993.00540020040015. [DOI] [PubMed] [Google Scholar]
  14. Devanand D. P., Dwork A. J., Hutchinson E. R., Bolwig T. G., Sackeim H. A. Does ECT alter brain structure? Am J Psychiatry. 1994 Jul;151(7):957–970. doi: 10.1176/ajp.151.7.957. [DOI] [PubMed] [Google Scholar]
  15. Frank E., Prien R. F., Jarrett R. B., Keller M. B., Kupfer D. J., Lavori P. W., Rush A. J., Weissman M. M. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991 Sep;48(9):851–855. doi: 10.1001/archpsyc.1991.01810330075011. [DOI] [PubMed] [Google Scholar]
  16. Grant R., Condon B., Lawrence A., Hadley D. M., Patterson J., Bone I., Teasdale G. M. Human cranial CSF volumes measured by MRI: sex and age influences. Magn Reson Imaging. 1987;5(6):465–468. doi: 10.1016/0730-725x(87)90380-8. [DOI] [PubMed] [Google Scholar]
  17. Gundersen H. J., Bendtsen T. F., Korbo L., Marcussen N., Møller A., Nielsen K., Nyengaard J. R., Pakkenberg B., Sørensen F. B., Vesterby A. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS. 1988 May;96(5):379–394. doi: 10.1111/j.1699-0463.1988.tb05320.x. [DOI] [PubMed] [Google Scholar]
  18. HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56–62. doi: 10.1136/jnnp.23.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jeste D. V., Lohr J. B., Goodwin F. K. Neuroanatomical studies of major affective disorders. A review and suggestions for further research. Br J Psychiatry. 1988 Oct;153:444–459. doi: 10.1192/bjp.153.4.444. [DOI] [PubMed] [Google Scholar]
  20. Kobayashi S., Okada K., Yamashita K. Incidence of silent lacunar lesion in normal adults and its relation to cerebral blood flow and risk factors. Stroke. 1991 Nov;22(11):1379–1383. doi: 10.1161/01.str.22.11.1379. [DOI] [PubMed] [Google Scholar]
  21. Kovar M. G. Health of the elderly and use of health services. Public Health Rep. 1977 Jan-Feb;92(1):9–19. [PMC free article] [PubMed] [Google Scholar]
  22. Krishnan K. R., Doraiswamy P. M., Figiel G. S., Husain M. M., Shah S. A., Na C., Boyko O. B., McDonald W. M., Nemeroff C. B., Ellinwood E. H., Jr Hippocampal abnormalities in depression. J Neuropsychiatry Clin Neurosci. 1991 Fall;3(4):387–391. doi: 10.1176/jnp.3.4.387. [DOI] [PubMed] [Google Scholar]
  23. Mayhew T. M. A review of recent advances in stereology for quantifying neural structure. J Neurocytol. 1992 May;21(5):313–328. doi: 10.1007/BF01191700. [DOI] [PubMed] [Google Scholar]
  24. Mayhew T. M., Olsen D. R. Magnetic resonance imaging (MRI) and model-free estimates of brain volume determined using the Cavalieri principle. J Anat. 1991 Oct;178:133–144. [PMC free article] [PubMed] [Google Scholar]
  25. Meldrum B. S., Vigouroux R. A., Brierley J. B. Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons. Arch Neurol. 1973 Aug;29(2):82–87. doi: 10.1001/archneur.1973.00490260026003. [DOI] [PubMed] [Google Scholar]
  26. Nemeroff C. B., Widerlöv E., Bissette G., Walléus H., Karlsson I., Eklund K., Kilts C. D., Loosen P. T., Vale W. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984 Dec 14;226(4680):1342–1344. doi: 10.1126/science.6334362. [DOI] [PubMed] [Google Scholar]
  27. Rabins P. V., Pearlson G. D., Aylward E., Kumar A. J., Dowell K. Cortical magnetic resonance imaging changes in elderly inpatients with major depression. Am J Psychiatry. 1991 May;148(5):617–620. doi: 10.1176/ajp.148.5.617. [DOI] [PubMed] [Google Scholar]
  28. Rice J. P., Endicott J., Knesevich M. A., Rochberg N. The estimation of diagnostic sensitivity using stability data: an application to major depressive disorder. J Psychiatr Res. 1987;21(4):337–345. doi: 10.1016/0022-3956(87)90080-x. [DOI] [PubMed] [Google Scholar]
  29. Rothschild A. J., Benes F., Hebben N., Woods B., Luciana M., Bakanas E., Samson J. A., Schatzberg A. F. Relationships between brain CT scan findings and cortisol in psychotic and nonpsychotic depressed patients. Biol Psychiatry. 1989 Oct;26(6):565–575. doi: 10.1016/0006-3223(89)90081-4. [DOI] [PubMed] [Google Scholar]
  30. Sapolsky R. M., Krey L. C., McEwen B. S. Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci. 1985 May;5(5):1222–1227. doi: 10.1523/JNEUROSCI.05-05-01222.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sapolsky R. M., Krey L. C., McEwen B. S. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986 Aug;7(3):284–301. doi: 10.1210/edrv-7-3-284. [DOI] [PubMed] [Google Scholar]
  32. Sheline Y. I. High prevalence of physical illness in a geriatric psychiatric inpatient population. Gen Hosp Psychiatry. 1990 Nov;12(6):396–400. doi: 10.1016/0163-8343(90)90008-z. [DOI] [PubMed] [Google Scholar]
  33. Starkman M. N., Gebarski S. S., Berent S., Schteingart D. E. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome. Biol Psychiatry. 1992 Nov 1;32(9):756–765. doi: 10.1016/0006-3223(92)90079-f. [DOI] [PubMed] [Google Scholar]
  34. Warshaw M. G., Klerman G. L., Lavori P. W. Are secular trends in major depression an artifact of recall? J Psychiatr Res. 1991;25(3):141–151. doi: 10.1016/0022-3956(91)90007-w. [DOI] [PubMed] [Google Scholar]
  35. Watanabe Y., Gould E., McEwen B. S. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res. 1992 Aug 21;588(2):341–345. doi: 10.1016/0006-8993(92)91597-8. [DOI] [PubMed] [Google Scholar]
  36. Watson C., Andermann F., Gloor P., Jones-Gotman M., Peters T., Evans A., Olivier A., Melanson D., Leroux G. Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging. Neurology. 1992 Sep;42(9):1743–1750. doi: 10.1212/wnl.42.9.1743. [DOI] [PubMed] [Google Scholar]
  37. Woolley C. S., Gould E., McEwen B. S. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res. 1990 Oct 29;531(1-2):225–231. doi: 10.1016/0006-8993(90)90778-a. [DOI] [PubMed] [Google Scholar]
  38. Yehuda R., Kahana B., Binder-Brynes K., Southwick S. M., Mason J. W., Giller E. L. Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry. 1995 Jul;152(7):982–986. doi: 10.1176/ajp.152.7.982. [DOI] [PubMed] [Google Scholar]
  39. Yehuda R., Southwick S. M., Nussbaum G., Wahby V., Giller E. L., Jr, Mason J. W. Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis. 1990 Jun;178(6):366–369. doi: 10.1097/00005053-199006000-00004. [DOI] [PubMed] [Google Scholar]
  40. Young E. A., Akana S., Dallman M. F. Decreased sensitivity to glucocorticoid fast feedback in chronically stressed rats. Neuroendocrinology. 1990 May;51(5):536–542. doi: 10.1159/000125388. [DOI] [PubMed] [Google Scholar]
  41. Young E. A., Haskett R. F., Murphy-Weinberg V., Watson S. J., Akil H. Loss of glucocorticoid fast feedback in depression. Arch Gen Psychiatry. 1991 Aug;48(8):693–699. doi: 10.1001/archpsyc.1991.01810320017003. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES