Elsevier

Biological Psychiatry

Volume 61, Issue 5, 1 March 2007, Pages 640-652
Biological Psychiatry

Original article
Parvalbumin Neurons in the Entorhinal Cortex of Subjects Diagnosed With Bipolar Disorder or Schizophrenia

https://doi.org/10.1016/j.biopsych.2006.04.026Get rights and content

Background

Growing evidence indicates that the entorhinal cortex (ECx) might be affected in schizophrenia (SZ) and bipolar disorder (BD). To test whether distinct interneuronal subpopulations might be altered, numbers of parvalbumin-immunoreactive (PVB-IR) neurons were measured in the ECx of BD and SZ subjects. These neurons play a pivotal role within ECx intrinsic circuits.

Methods

Numbers, numerical density, and soma size of PVB-IR neurons were measured in the ECx of normal control (n = 16), BD (n = 10), and SZ (n = 10) subjects. The volume of the ECx was measured in Nissl-stained sections.

Results

In BD, decreases of total numbers (p = .02) and numerical densities (p = .01) of PVB-IR neurons were detected in the ECx. Within distinct subregions, reductions were detected in the superficial layers of the lateral (p = .02), intermediate (p = .04), and caudal (p = .01) ECx. In SZ, total numbers and numerical densities were not altered. A reduction of soma size was present in the intermediate ECx (p = .01). Volume was unaffected in either disorder.

Conclusions

In BD, a decrease of PVB-IR neurons may alter intrinsic inhibitory networks within the superficial layers of the ECx. The likely consequence is a disruption of integration and transfer of information from the cerebral cortex to the hippocampus.

Section snippets

Human Subjects

Postmortem tissue blocks containing the whole ECx from 10 SZ, 10 BD, and 16 normal control donors (one hemisphere/subject) were obtained from the Harvard Brain Tissue Resource Center, Belmont, Massachusetts (Table 1). Diagnoses were made by retrospective review of medical records and an extensive questionnaire about social and medical history provided by family members of the donor. In combination, these records provided information on each subject starting from the onset of the disease or

ECx Volume

The volume (mean ± SD) of the ECx was not found to be altered in BD (315.59 ± 82.7 mm3) or SZ (318.35 ± 148.9 mm3), in comparison with normal control subjects (304.04 ± 134.4 mm3) (Figure 3). The values measured in our study are consistent with those reported by other research groups (Bussiere et al 2002, Krimer et al 1997). Brain weight was found to be a significant covariate (p = .01) and was included in the baseline regression model. None of the other covariates were found to have

Discussion

These results indicate that the Tn and Nd of PVB-IR neurons are decreased in the ECx of BD patients. To our knowledge, this is the first evidence for a disruption of inhibitory intrinsic PVB-IR neurons in the ECx of BD subjects. No significant changes were detected in SZ subjects, with the exception of a cell size decrease restricted to the ECx-I.

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      While PV cell number, density, and NR2A expression in PV cells were not found to be altered (Alcaide et al., 2019; Bitanihirwe et al., 2010; Sakai et al., 2008), there was evidence of reduced PV mRNA expression compared with psychiatrically healthy controls reported in three studies (Chung et al., 2018; Sibille et al., 2011; Volk et al., 2016), although in Sibille et al.’s study this effect was eliminated by the exclusion of case-control pairs with potentially confounding factors. Two investigations of the amygdalar subfields in BD patients have, for the most part, reported no change in PV cell number or density (Berretta et al., 2015; Pantazopoulos et al., 2007). The only discrepancy was in the lateral amygdalar nucleus, where Berretta et al. (2015) reported decreased PV cell density compared to controls, whereas the same team earlier reported no change between groups (Pantazopoulos et al., 2007).

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