Histological examination of choroid plexus epithelia changes in schizophrenia

• Published in: Brain, behavior, and immunity Vol. 111; pp. 292 - 297
• Main Authors: Williams, M.R., Macdonald, C.M., Turkheimer, F.E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2023
• Subjects: Brain - metabolism; Central Nervous System - metabolism; Choroid Plexus; Choroid Plexus - metabolism; Depressive Disorder, Major - metabolism; Dopamine; Humans; Major depressive Disorder; Pathology; Schizophrenia; Schizophrenia - metabolism; Schizophrenia; Pathology; Dopamine; Major depressive Disorder; Choroid Plexus
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.04.016

•The choroid plexus has a key role in the production of the cerebrospinal fluid and the interaction between systemic and central immunity.•A number of imaging studies have identified volumetric abnormalities of the choroid plexus in neurodegenerative and neurodevelopmental disorders, in schizophrenia in particular.•This work carried out the histological characterization of the epithelial cells of the choroid plexus in patients with schizophrenia, major depression and matched controls.•Results confirm increased somal width in patients with schizophrenia but not in major depression. Specifically, increased epithelial cell width was demonstrated in patients without psychotic medication.•These results suggest an illness mediated change likely mediated by the dopaminergic system that, from experimental work in animal models, has been shown to have a role in the modulation of choroid plexus function. The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes 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. 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 (NPD). FFPE blocks were sectioned at 7 μm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected at x600 magnification. Calcification was assessed in all CP regions manually. Analysis with a General Linear Model demonstrated a significant effect of diagnosis on somal width (p = 0.006, R2 = 0.33 R2(adj) = 0.25) demonstrating increased somal width in SZ without psychotic medication versus controls (p = 0.032), but not in medicated SZ cases. No effects were observed in calcification. The epithelial cells that were examined were attached to the CP fibrous surface, so width expansion describes the primary methods for these cells to expand with adherence to this surface in SZ. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change mediated through the DA-system with likely neuronal origin. CP alterations were not found in MDD where they are instead generally associated with heightened allostatic load that was unknown in this cohort.