Archival ReportN-Methyl-D-Aspartate Receptor and Calbindin-Containing Neurons in the Anterior Cingulate Cortex in Schizophrenia and Bipolar Disorder
Section snippets
Subjects
A cohort of 60 human brains from 20 subjects with schizophrenia, 20 subjects with bipolar disorder, and 20 normal control subjects were obtained from the Harvard Brain Tissue Resource Center at McLean Hospital, Belmont, Massachusetts (Supplement 1). Each group of subjects with schizophrenia or bipolar disorder was matched to a normal control group on the basis of age, postmortem interval (PMI), and whenever possible, gender and side of hemisphere. The mean freezer storage time (days ± SD) of
Statistical Analyses
The densities of CB+ single- labeled neurons were compared between subject groups across layers 2 through 6 with repeated-measures analysis of variance (ANOVA), with diagnosis as the between-groups factor, layer as the within-group factor, and repeated measures on layer. For the CB+/NR2A+ double-labeled neurons, to test the a priori hypothesis that the density of these neurons would be significantly decreased in layer 2 in subjects with schizophrenia and bipolar disorder, a one-way analysis of
Density of All CB+ Neurons
Our repeated-measures ANOVA model failed to reveal any significant diagnosis effect [F(2,57) = 1.09; p = .34] on the density of these neurons (Figure 1).
Density of CB+/NR2A+ Neurons
The ANOVA performed on layer 2 revealed that the effect of diagnosis was highly significant [F(2,57) = 4.33; p = .018; Figure 2]. Post hoc unpaired t tests further revealed that the density of these neurons was significantly increased in schizophrenia by 41% and 44%, respectively, compared with the normal control (p = .012) and bipolar disorder
Discussion
We have previously found that, in layer 2 of the ACCx, the expression of NR2A mRNA in approximately 53% and 35% of the GABA cells in schizophrenia and bipolar disorder, respectively, seems to be decreased to a level that is no longer experimentally detectable (9). Because CB-containing GABA cells tend to be more heavily localized to layer 2 of the cortex (16, 19, 20), we hypothesized that they would be among the GABA neurons that are affected. Our data suggest that, contrary to this hypothesis,
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2016, Biological PsychologyCitation Excerpt :While the studies reviewed using total homogenate or film-based in situ hybridization techniques suggest that the NR2A subunit of the NMDA receptor is not greatly altered in people with schizophrenia, two studies of NR2A subunit mRNA in interneurons suggest otherwise. Using double-label in situ hybridization to define interneuron populations, Woo et al. (2004); Woo, Shrestha, Lamb, Minns, and Benes (2008) found a decreased density of NR2A mRNA expressing GAD67 positive interneurons, but an increased density in the subset of NR2A and calbindin mRNA-containing neurons in layer II of anterior cingulate cortex. This is noteworthy, as the gene for NR2A has been implicated in the etiology of schizophrenia in large genetics studies (Fromer et al., 2014; Ripke et al., 2014).