Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

Althubaity, Noha, Schubert, Julia, Martins, Daniel, Yousaf, Tayyabah, Nettis, Maria A., Mondelli, Valeria, Pariante, Carmine, Harrison, Neil A. ORCID: https://orcid.org/0000-0002-9584-3769, Bullmore, Edward T., Dima, Danai, Turkheimer, Federico E. and Veronese, Mattia 2021. Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression. NeuroImage: Clinical 33 , 102926. 10.1016/j.nicl.2021.102926

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Abstract

Background Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. Results We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. Conclusion This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher:	Elsevier
ISSN:	2213-1582
Date of First Compliant Deposit:	8 March 2022
Date of Acceptance:	21 December 2021
Last Modified:	12 May 2023 18:13
URI:	https://orca.cardiff.ac.uk/id/eprint/148117

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