Decreased
density of pyramidal neurons in the
orbitofrontal cortex of elderly subjects with
depression
Neuroimaging
studies have shown that elderly (aged > 60
years) patients with depression have reductions
in the volume of prefrontal cortex and
orbitofrontal cortex (ORB). Elderly depressed
patients also have more frontal white matter and
basal ganglia hyperintensities than age-matched
nondepressed control subjects. The aim of a
study was to evaluate neuronal pathology of the
ORB in elderly patients with a diagnosis of
major depressive disorder (MDD) compared with
control subjects.
Postmortem samples from the left ORB were
collected at autopsies from 15 elderly (average
age, 75 years) subjects with MDD and 11
age-matched control subjects (average age, 72
years). Tissue sections were cut, stained, and
selected for cell counting. The density of
neurons and glial cells, the density of
pyramidal and nonpyramidal neurons, and the
thickness of the cortex and relative width of
each of its layers, were measured.
The density of pyramidal neurons was
significantly reduced (by 30%) in depressed as
compared with controls, whereas the density of
nonpyramidal neurons was unaffected in
depression. Further analysis of the laminar
density of pyramidal neurons revealed that in
MDD the density of pyramidal neurons in layers
II–VI was reduced, as compared with control
subjects (30% in layers IIIc and V). In
contrast, the density of glial cells and the
cortical thickness in the depressed group were
similar to those of the control group.
The density of neurons with pyramidal morphology
in the ORB is low in elderly subjects with MDD
as compared with control subjects. The most
severe pathology in cortical layers III and V
that contain pyramidal neuron cell bodies is
particularly relevant since they giving rise to
prefronto-striatal and prefronto-cortical
projections. Degeneration of these neurons might
therefore play a role in the pathophysiology of
depression in the elderly. Rajkowska
G, Miguel-Hidalgo JJ, Dubey P, Stockmeier CA,
Krishnan KR. Prominent reduction in pyramidal
neurons density in the orbitofrontal cortex of
elderly depressed patients. Biol Psychiatry
2005, Jun 10.