Background: Depression is often associated with elevations of peripheral inflammatory markers [1]but the mechanisms linking peripheral inflammation and changes in the central nervous system are still under investigation. Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in brain homeostasis, and mediating the interaction between central and peripheral inflammation [2, 3]. Here we aimed to investigate CP volume alterations in depression and their associations with central brain inflammation. 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 blood-to-CSF radiotracer exchange parameters, and CPvolume, respectively. We leveraged transcriptomic data from the Allen Human Brain Atlas to explore possible associations between the brain map depicting the correlations between CP volume and TSPO with functional brain pathways. We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) =+2.17, p=0.03) that was positively correlated with [11C]PK11195 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) [Figure]. The CP volume exhibited a negative association with the blood-to-CSF radiotracer exchange parameters(r=-0.28, p=0.02). Integration of transcriptomic data with CP volume/TSPO imaging correlation map showed significant gene enrichment for several pathways involved in the neuroinflammatory response. These results support the hypothesis that changes in brain barriers may cause a reduction in solute exchanges between blood and CSF, disturbing brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders [4, 5] these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

Acknowledgements

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References

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