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. 2010 Mar 1;67(5):465-70.
doi: 10.1016/j.biopsych.2009.10.027. Epub 2009 Dec 9.

Reduced density of calbindin immunoreactive GABAergic neurons in the occipital cortex in major depression: relevance to neuroimaging studies

Dorota Maciag  1 , Jonathan Hughes, Gillian O'Dwyer, Yilianys Pride, Craig A Stockmeier, Gerard Sanacora, Grazyna Rajkowska
Affiliations

Reduced density of calbindin immunoreactive GABAergic neurons in the occipital cortex in major depression: relevance to neuroimaging studies

Dorota Maciag et al. Biol Psychiatry. .

Abstract

Background: Several lines of evidence suggest dysfunction of the gamma-aminobutyric acid (GABA)ergic system in major depressive disorder. Neuroimaging studies report reduced levels of GABA in the dorsolateral prefrontal and occipital cortex of depressed patients. Our previous postmortem study revealed a reduction in the density and size of calbindin-immunoreactive (CB-IR) GABAergic neurons in the prefrontal cortex in major depressive disorder. The goal of this study was to test whether the changes in CB-IR neurons can also be detected in the occipital cortex, where neuroimaging studies report a prominent GABA decrease.

Methods: A three-dimensional cell counting probe was used to assess the cell-packing density and size of CB-IR neurons in layer II of the occipital cortex in 10 major depressive disorder subjects and 10 psychiatrically healthy control subjects.

Results: The density of CB-IR neurons was significantly decreased by 28% in major depressive disorder subjects compared with the control group. The size of CB-IR neurons was unchanged in major depressive disorder subjects when compared with control subjects.

Conclusions: The reduction in the density of CB-IR GABAergic neurons in the occipital cortex in depression is similar to that observed previously in the prefrontal cortex. Deficit in cortical GABAergic interneurons may contribute to the low GABA levels detected in neuroimaging studies in major depressive disorder patients.

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Figures

Figure 1
Figure 1
a: Nissl stained section of a non-psychiatric control subject showing the typical cytoarchitectonic features of area 17. b: CB immunoreactive neurons in control subject (adjacent section to Nissl). c: CB immunoreactive neurons in MDD subject. Note that the majority of CB-IR neurons are localized to layer II and in a smaller number to the upper part of layer III. Images were obtained using the ×4 objective, scale bar = 125 μm.
Figure 2
Figure 2
Cell packing density of CB-IR neurons in the occipital cortex (Brodmann's area 17) of control and MDD subjects. Values for the individual subjects (circles) and mean values (horizontal lines) are presented.
Figure 3
Figure 3
Cell packing density of CB-IR neurons in the occipital cortex (Brodmann's area 17) of control, MDD suicide (MDDs) and MDD non suicide (MDD ns). Values for the individual subjects (circles) and mean values (horizontal lines) are presented. Note that the mean values for CB-IR neurons density are comparable between MDD suicide and MDD non suicides (unpaired t-test, t=0.048, df=8, p= 0.96; Mann Whitney test, Z=0.0, p=1).
Figure 4
Figure 4
Size of CB-IR neurons in the occipital cortex (Brodmann's area 17) of control and MDD subjects. Values for the individual subjects (circles) and mean values (horizontal lines) are presented.
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