title: Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus.
abstract: In major depression, decreased hippocampal volume has been attributed to hypercortisolemia, a frequent sign of the disorder, because in animals an excess of corticosteroids has led to dendritic atrophy, astrogliosis and loss of neurons in this brain region. The present study is the first to investigate the structural integrity of the human hippocampus in major depression and following glucocorticoid treatment. Post-mortem hippocampal tissue from 15 patients who had had major depression or bipolar affective disorder, 10 patients who had been treated with glucocorticoids and 16 controls was assessed using haematoxylin-eosin, Nissl and Bodian staining. The patterns of reactive astrogliosis (glial fibrillary acidic protein, GFAP), synaptic density (synaptophysin), synaptic reorganization (growth-associated protein B-50) and early signs of Alzheimer's disease (Alz-50) were examined immunocytochemically. Multivariate analysis, with the patients' age, tissue fixation time and postmortem delay as covariates, was performed. There was no evidence of neuronal cell loss or other major morphological alterations in any of the groups, nor was there a significant change in the distribution pattern of synaptophysin or Alz-50. Changes in B-50 and GFAP staining were observed in the steroid-treated and depressed patients in areas CA1 and CA2 only. The human hippocampus in major depression and after glucocorticoid treatment does not reveal any major morphological changes or signs of neuronal cell death, but does show subtle alterations in B-50 and GFAP expression in selected parts of the pyramidal cell layer.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. muellerm@mpipsykl.mpg.de
authors.forename: M B
authors.initials: MB
authors.lastname: Müller
authors.forename: P J
authors.initials: PJ
authors.lastname: Lucassen
authors.forename: A
authors.initials: A
authors.lastname: Yassouridis
authors.forename: W J
authors.initials: WJ
authors.lastname: Hoogendijk
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
authors.forename: D F
authors.initials: DF
authors.lastname: Swaab
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D003866:Depressive Disorder / Q000473:pathology*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005938:Glucocorticoids / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: C056167:Alzheimer's disease antigen; D000941:Antigens; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D005938:Glucocorticoids; D016708:Synaptophysin