Histological examination of choroid plexus epithelia changes in schizophrenia

Abstract

Background. The choroid plexus (CP) is suggested to be involved in neuroimmune regulation avia the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP change in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. Methods. Formalin-fixed paraffin-embedded FFPE blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls. FFPE blocks were sectioned at 7μm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected x600 magnification. Calcification was assessed in all CP regions manually. Results. Linear General Model analysis shows a significant effect of diagnosis on somal width (p=0.006, r2=0.33, adj=0.25), with a significant difference between SZ non-medicated v nonmedicated NPD controls (p=0.032), demonstrating increased somal width in SZ with psychotic medication but not in unmedicated SZ cases. No effects were observed in calcification. Discussion. Epithelial cells examined were adhered to CP fibrous surface so width expansion describes the primary methods for these cells to expand with adherence to this surface. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness specific change and mediated through the DA-system, although the mechanism is unclear at present.

Investigation of choroid plexus variability in schizophrenia-spectrum disorders – insights from a multimodal study

“…In line with those findings, increased ChP volumes, altered ChP epithelia, and associated upregulation of immune genes in the ChP were described in individuals with SSD 14–16 . Located in each brain ventricle, the ChP produces CSF and forms the BCB, thus regulating central nervous system (CNS) homeostasis 17 .…”

“…Even though we showed a moderate correlation between FreeSurfer segmentation and manual segmentation of ChP, some authors have questioned the reliability of FreeSurfer segmentation of ChP and have suggested other more reliable methods 43, 59 . Furthermore, since only nine of the individuals with SSD in our cohort were antipsychotic-naïve, we cannot exclude medication effects on choroid plexus morphology 21 . The individual clusters (especially cluster 1) might have been underpowered to detect differences regarding clinical and immunological features.…”