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

Noha Althubaity; Julia Schubert; Daniel Martins; Tayyabah Yousaf; Maria A Nettis; Valeria Mondelli; Carmine Pariante; Neil A Harrison; Edward T Bullmore; Danai Dima; Federico E Turkheimer; Mattia Veronese

doi:10.1016/j.nicl.2021.102926

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

Noha Althubaity, Julia Schubert, Daniel Martins, Tayyabah Yousaf, Maria A Nettis, Valeria Mondelli, Carmine Pariante, Neil A Harrison, Edward T Bullmore, Danai Dima, Federico E Turkheimer, Mattia Veronese

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	102926
Journal	NeuroImage. Clinical
Volume	33
DOIs	https://doi.org/10.1016/j.nicl.2021.102926
Publication status	Published - 2022

Keywords

Blood-Brain Barrier/diagnostic imaging
Choroid Plexus/diagnostic imaging
Depression/diagnostic imaging
Humans
Neuroinflammatory Diseases
Permeability

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.nicl.2021.102926

Cite this

Althubaity, N., Schubert, J., Martins, D., Yousaf, T., Nettis, M. A., Mondelli, V., Pariante, C., Harrison, N. A., Bullmore, E. T., Dima, D., Turkheimer, F. E., & Veronese, M. (2022). Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression. NeuroImage. Clinical, 33, 102926. https://doi.org/10.1016/j.nicl.2021.102926

@article{32a1d6cb6c714559915308da2b60d891,

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

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.",

keywords = "Blood-Brain Barrier/diagnostic imaging, Choroid Plexus/diagnostic imaging, Depression/diagnostic imaging, Humans, Neuroinflammatory Diseases, Permeability",

author = "Noha Althubaity and Julia Schubert and Daniel Martins and Tayyabah Yousaf and Nettis, {Maria A} and Valeria Mondelli and Carmine Pariante and Harrison, {Neil A} and Bullmore, {Edward T} and Danai Dima and Turkheimer, {Federico E} and Mattia Veronese",

year = "2022",

doi = "10.1016/j.nicl.2021.102926",

language = "English",

volume = "33",

pages = "102926",

journal = "NeuroImage. Clinical",

issn = "2213-1582",

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Althubaity, N , Schubert, J , Martins, D , Yousaf, T , Nettis, MA , Mondelli, V , Pariante, C, Harrison, NA, Bullmore, ET, Dima, D , Turkheimer, FE & Veronese, M 2022, 'Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression', NeuroImage. Clinical, vol. 33, pp. 102926. https://doi.org/10.1016/j.nicl.2021.102926

TY - JOUR

T1 - Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

AU - Althubaity, Noha

AU - Schubert, Julia

AU - Martins, Daniel

AU - Yousaf, Tayyabah

AU - Nettis, Maria A

AU - Mondelli, Valeria

AU - Pariante, Carmine

AU - Harrison, Neil A

AU - Bullmore, Edward T

AU - Dima, Danai

AU - Turkheimer, Federico E

AU - Veronese, Mattia

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Blood-Brain Barrier/diagnostic imaging

KW - Choroid Plexus/diagnostic imaging

KW - Depression/diagnostic imaging

KW - Humans

KW - Neuroinflammatory Diseases

KW - Permeability

U2 - 10.1016/j.nicl.2021.102926

DO - 10.1016/j.nicl.2021.102926

M3 - Article

C2 - 34972034

SN - 2213-1582

VL - 33

SP - 102926

JO - NeuroImage. Clinical

JF - NeuroImage. Clinical

ER -

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

Abstract

Keywords

UN SDGs

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