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

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 [ 11 C]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 [ 11 C]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.

Abstract licence: CC BY-NC

1. 2.

   Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder · 2015

2. 16.

   Development of the choroid plexus and blood-CSF barrier · 2015

3. 19.

   Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity · 2009

4. 59.

   Adolescent Tuning of Association Cortex in Human Structural Brain Networks · 2017

5. 64.

   ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing · 2020

6. 65.

   The Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Psychiatric Disorders · 2019

7. 69.

   Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders · 2020

8. 71.

   Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients · 2020

9. 73.

   Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: results from a double-blind randomised clinical trial · 2021

74 more references, whose wording the paper’s licence keeps private.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.