Citation

Cobb JA, O'Neill K, Milner J, Mahajan GJ, Lawrence TJ, May WL, Miguel-Hidalgo J, Rajkowska G, Stockmeier CA. Neuroscience 2015; 316: 209-220.

Affiliation

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: cstockmeier@umc.edu.

Copyright

(Copyright © 2015, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.neuroscience.2015.12.044

PMID

26742791

Abstract

Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with MDD and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels.

Language: en