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uring the past two decades, anatomical sub-
strates associated with the neuropathology of mood dis-
orders have been revealed through both in vivo neuro-
imaging studies and morphological and neurochemical
studies on postmortem brain tissue.While neuroimaging
studies have given significant insight into the gross mor-
phological location of dysfunctional brain regions in
depression, the neurochemical, cellular, and molecular
features of depression are being unlocked by studies in
postmortem brain tissue.
Novel studies at the microscopic level are establishing
that the mood disorders are associated with abnormali-
ties in cell morphology and distribution, in addition to the
long-recognized neurochemical abnormalities. Major
depressive disorder (MDD) and bipolar disorder (BPD)
have been examined in postmortem brain tissue by sev-
eral laboratories in the past 6 years. Cell-counting stud-
ies report changes in the density and size of both neurons
and glia in a number of frontolimbic brain regions,
including dorsolateral prefrontal, orbitofrontal, and ante-
rior cingulate cortex, and the amygdala and hippocam-
pus. These studies in postmortem brain tissue confirm
and extend structural and functional neuroimaging stud-
ies that reveal volumetric and metabolic changes in the
same frontolimbic brain regions in the same disorders.
Convergence of cellular changes at the microscopic level
with neuroimaging changes detected in vivo provides a
compelling integration of clinical and basic research for
disentangling the pathophysiology of depression.
Regionally localized and cell typespecific changes in
neuronal and glial cytoarchitecture recently identified in
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C l i n i c a l r e s e a r c h
D
Copyright © 2004 LLS SAS. All rights reserved
www.dialogues-cns.org
Cellular abnormalities in depression:
evidence from postmortem brain tissue
Craig A. Stockmeier, PhD; Grazyna Rajkowska, PhD
Keywords:
major depression; bipolar disorder; postmortem brain; glia; neuron;
neuropathology
Author affiliations:
The University of Mississippi Medical Center, Department
of Psychiatry and Human Behavior, Jackson, Miss, USA
Address for correspondence:
Craig Stockmeier, PhD, Department of Psychiatry
and Human Behavior, University of Mississippi Medical Center, 2500 N State St,
Box 127, Jackson, MS 39216, USA
(e-mail: cstockmeier@psychiatry.umsmed.edu)
During the past two decades, in vivo neuroimaging stud-
ies have permitted significant insights into the general
location of dysfunctional brain regions in depression. In
parallel and often intersecting ways, neuroanatomical,
pharmacological, and biochemical studies of postmortem
brain tissue are permitting new insights into the patho-
physiology of depression. In addition to long-recognized
neurochemical abnormalities in depression, novel studies
at the microscopic level support the contention that mood
disorders are associated with abnormalities in cell mor-
phology and distribution. In the past 6 years, cell-counting
studies have identified changes in the density and size of
both neurons and glia in a number of frontolimbic brain
regions, including dorsolateral prefrontal, orbitofrontal,
and anterior cingulate cortex, and the amygdala and hip-
pocampus. Convergence of cellular changes at the micro-
scopic level with neuroimaging changes detected in vivo
provides a compelling integration of clinical and basic
research for disentangling the pathophysiology of depres-
sion. The ultimate integration of these two research
approaches will occur with premortem longitudinal clini-
cal studies on well-characterized patients linked to post-
mortem studies of the same subjects.
© 2004, LLS SAS
Dialogues Clin Neurosci
. 2004;6:185-197.