Elsevier

Biological Psychiatry

Volume 67, Issue 5, 1 March 2010, Pages 465-470
Biological Psychiatry

Archival Report
Reduced Density of Calbindin Immunoreactive GABAergic Neurons in the Occipital Cortex in Major Depression: Relevance to Neuroimaging Studies

https://doi.org/10.1016/j.biopsych.2009.10.027Get rights and content

Background

Several lines of evidence suggest dysfunction of the γ-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.

Section snippets

Human Subjects

Postmortem brain samples were collected at autopsy at the Cuyahoga County Coroner's Office in Cleveland, Ohio, from 20 subjects. Informed written consent was obtained from the legal next-of-kin of all subjects. Next-of-kin were interviewed and retrospective psychiatric assessments were conducted in accordance with Institutional Review Board policies, as described previously (12). Ten subjects met clinical criteria for MDD, and the other 10 subjects (termed normal control subjects) did not meet

Results

The density of CB-IR neurons was significantly reduced by 28% in the MDD subjects (21.2 ± 2.7 neurons × 103/mm3) compared with the age-matched control group [29.5 ± 2.2 neurons × 103/mm3; ANCOVA, F(1,14) = 7.58, p = .016] (Figure 1, Figure 2). The reduced density in MDD subjects does not appear to be specifically related to death by suicide because there was almost no difference in the mean density of CB-IR neurons between the six MDD suicide (20.8 ± 3.0 neurons × 103/mm3) and four MDD

Discussion

The present study demonstrates marked (28%) reductions in the density of CB-IR neurons in layer II of the occipital cortex in MDD subjects compared with control subjects. However, the size of CB-IR neurons was not significantly different between the two groups. All (but one) of our MDD subjects were free of antidepressants at the time of death as revealed by postmortem toxicology screening, suggesting this was largely a medication-free population. This deficit in GABA neurons is consistent with

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