Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder

Although major depressive disorder (MDD) and schizophrenia (SZ) are closely associated with disrupted functions in frontal and limbic areas of cerebral cortex, cellular pathology has also been found in other brain areas, including primary sensory cortex. Auditory cortex is of particular interest, given the prominence of auditory hallucinations in SZ, and sensory deficits in MDD. We used stereological sampling methods in auditory cortex to look for cellular differences between MDD, SZ and non-psychiatric subjects. Additionally, as all of our MDD subjects died of suicide, we evaluated the association of suicide with our measurements by selecting a SZ sample that was divided between suicide and non-suicide subjects. Measurements were done in primary auditory cortex (area A1) and auditory association cortex (area Tpt), two areas with distinct roles in sensory processing and obvious differences in neuron density and size. In MDD, densities of GABAergic interneurons immunolabeled for calretinin (CR) and calbindin (CB) were 23-29% lower than non-psychiatric controls in both areas. Parvalbumin (PV) interneurons (counted only in area Tpt) showed a nominally smaller (16%) reduction that was not statistically significant. Total neuron and glia densities measured in Nissl stained sections did not show corresponding reductions. Analysis of suicide in the SZ sample indicated that reduced CR cell density was associated with suicide, whereas the densities of CB and other cells were not. Our results are consistent with previous studies in MDD that found altered GABA-associated markers throughout the cerebral cortex including primary sensory areas.