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

Background and Hypothesis Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions, associated with peripheral inflammation in SSD. Study Design A cross-sectional cohort of 132 individuals with SSD and 107 age-matched healthy controls (HC) underwent magnetic resonance imaging (MRI) of the brain and clinical phenotyping to investigate the ChP and associated regions. Case-control comparison of ChP volumes was conducted and structural variance was analysed by employing the variability ratio (VR). K-means clustering analysis was used to identify subgroups with distinct patterns of the ventricular system and the clusters were compared in terms of demographic, clinical and immunological variables. The relationship between ChP volumes and brain regions, previously associated with peripheral inflammation, was investigated. Study Results We could not find a significant enlargement of the ChP in SSD compared to HC but detected an increased VR of ChP and lateral ventricle volumes. Based on these regions we identified 3 clusters with differences in age, symbol coding test scores and possibly peripheral neutrophil counts. Larger ChP volume was associated with higher volumes of hippocampus, putamen, and thalamus in SSD, but not in HC. Conclusions This study suggests that ChP variability, but not mean volume, is increased in individuals with SSD, compared to HC. Larger ChP volumes in SSD were associated with higher volumes of regions, previously associated with peripheral inflammation. ### Competing Interest Statement The authors declare that they have no biomedical financial interests or potential conflicts of interest regarding the content of this report. AH received paid speakership by Janssen, Otsuka, Lundbeck, and Recordati and was member of advisory boards of these companies and Rovi. AS has been an honorary speaker for TAD Pharma and Roche and a member of advisory boards for Roche. PF received paid speakership by Boehringer-Ingelheim, Janssen, Otsuka, Lundbeck, Recordati, and Richter and was member of advisory boards of these companies and Rovi. SP received previous speaker fees and/or travel expenses from Novartis Pharma GmbH, Oertli AG, Bayer AG, Alcon Pharma GmbH, and Pharm-Allergan GmbH. EW was invited to advisory boards from Recordati and Boehringer-Ingelheim. S.H. is supported by an Australian Research Training Program scholarship. D.S. is supported by an NHMRC Investigator Fellowship GNT 1194635. N.W. has received speaker fees from Otsuka, Lundbeck and Janssen. All other authors report no biomedical financial interests or potential conflicts of interest. ### Funding Statement This research was supported by the German Center for Mental Health (DZPG) Munich/Augsburg (Reg. N. 01EE2303A, 01EE2303F and 01EE2303C). The procurement of the Prisma 3T MRI scanner was supported by the Deutsche Forschungsgemeinschaft (DFG, INST 86/1739-1 FUGG). No funding was received by commercial or not-for-profit sectors. EB, IJ and MK were supported by doctoral scholarships from the Faculty of Medicine, LMU Munich, Munich, Germany. LK, IM and FJR were supported by the Else Kroener-Fresenius Foundation for the Residency/PhD track of the International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany. FJR, MC, JM were supported by the Foerderprogramm fuer Forschung und Lehre (FoeFoLe) of the Faculty of Medicine, LMU Munich, Munich, Germany. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This project was carried out as part of the Clinical Deep Phenotyping (CDP) study, an ongoing add-on study to the Munich Mental Health Biobank (project number 18-716) (German Clinical Trials Register, DRKS, ID: DRKS00024177) and approved by the ethics committee of the Faculty of Medicine, Ludwig-Maximilian University of Munich (project numbers 20-0528 and 22-0035). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.