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
N1 - Funding Information:
The BIODEP study was sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge, and funded by a strategic award from the Wellcome Trust (104025) in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Recruitment of participants was supported by the National Institute of Health Research (NIHR) Clinical Research Network: Kent, Surrey and Sussex & Eastern. E Bullmore and CM Pariante are supported by a Senior Investigator award from the NIHR. Additional funding was provided by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, and by the NIHR Cambridge Biomedical Research Centre (Mental Health). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Cambridge (70). We would like to gratefully thank all study participants, research teams and laboratory staff, without whom this research would not have been possible. We thank and acknowledge all members of the NIMA Consortium at the time of data collection: Dominika Wlazly, Amber Dickinson, Andy Foster, Clare Knight, Claire Leckey, Paul Morgan, Angharad Morgan, Caroline O'Hagan, Samuel Touchard, Shahid Khan, Phil Murphy, Christine Parker, Jai Patel, Jill Richardson, Paul Acton, Nigel Austin, Anindya Bhattacharya, Nick Carruthers, Peter de Boer, Wayne Drevets, John Isaac, Declan Jones, John Kemp, Hartmuth Kolb, Jeff Nye, Gayle Wittenberg, Gareth Barker, Anna Bogdanova, Heidi Byrom, Diana Cash, Annamaria Cattaneo, Daniela Enache, Tony Gee, Caitlin Hastings, Melisa Kose, Giulia Lombardo, Nicole Mariani, Anna McLaughlin, Valeria Mondelli, Maria Nettis, Naghmeh Nikkheslat, Carmine Pariante, Karen Randall, Julia Schubert, Luca Sforzini, Hannah Sheridan, Camilla Simmons, Nisha Singh, Federico Turkheimer, Vicky Van Loo, Mattia Veronese, Marta Vicente Rodriguez, Toby Wood, Courtney Worrell, Zuzanna Zajkowska, Brian Campbell, Jan Egebjerg, Hans Eriksson, Francois Gastambide, Karen Husted Adams, Ross Jeggo, Thomas Moeller, Bob Nelson, Niels Plath, Christian Thomsen, Jan Torleif Pederson, Stevin Zorn, Catherine Deith, Scott Farmer, John McClean, Andrew McPherson, Nagore Penandes, Paul Scouller, Murray Sutherland, Mary Jane Attenburrow, Jithen Benjamin, Helen Jones, Fran Mada, Akintayo Oladejo, Katy Smith, Rita Balice-Gordon, Brendon Binneman, James Duerr, Terence Fullerton, Veeru Goli, Zoe Hughes, Justin Piro, Tarek Samad, Jonathan Sporn, Liz Hoskins, Charmaine Kohn, Lauren Wilcock, Franklin Aigbirhio, Junaid Bhatti, Ed Bullmore, Roido Manavaki, Sam Chamberlain, Marta Correia, Anna Crofts, Tim Fryer, Martin Graves, Alex Hatton, Manfred Kitzbichler, Mary-Ellen Lynall, Christina Maurice, Ciara O'Donnell, Linda Pointon, Peter St George Hyslop, Lorinda Turner, Petra Vertes, Barry Widmer, Guy Williams, Jonathan Cavanagh, Alison McColl, Robin Shaw, Erik Boddeke, Alison Baird, Stuart Clare, Phil Cowen, I-Shu (Dante) Huang, Sam Hurley, Simon Lovestone, Alejo Nevado-Holgado, Elena Ribe, Anviti Vyas, Laura Winchester, Madeleine Cleal, Diego Gomez-Nicola, Renzo Mancuso, Hugh Perry, Mara Cercignani, Charlotte Clarke, Alessandro Colasanti, Neil Harrison, Rosemary Murray, Jason O'Connor, Howard Mount.
Funding Information:
The BIODEP study was sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge, and funded by a strategic award from the Wellcome Trust (104025) in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Recruitment of participants was supported by the National Institute of Health Research (NIHR) Clinical Research Network: Kent, Surrey and Sussex & Eastern. E Bullmore and CM Pariante are supported by a Senior Investigator award from the NIHR. Additional funding was provided by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, and by the NIHR Cambridge Biomedical Research Centre (Mental Health). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Cambridge (70). We would like to gratefully thank all study participants, research teams and laboratory staff, without whom this research would not have been possible. We thank and acknowledge all members of the NIMA Consortium at the time of data collection: Dominika Wlazly, Amber Dickinson, Andy Foster, Clare Knight, Claire Leckey, Paul Morgan, Angharad Morgan, Caroline O'Hagan, Samuel Touchard, Shahid Khan, Phil Murphy, Christine Parker, Jai Patel, Jill Richardson, Paul Acton, Nigel Austin, Anindya Bhattacharya, Nick Carruthers, Peter de Boer, Wayne Drevets, John Isaac, Declan Jones, John Kemp, Hartmuth Kolb, Jeff Nye, Gayle Wittenberg, Gareth Barker, Anna Bogdanova, Heidi Byrom, Diana Cash, Annamaria Cattaneo, Daniela Enache, Tony Gee, Caitlin Hastings, Melisa Kose, Giulia Lombardo, Nicole Mariani, Anna McLaughlin, Valeria Mondelli, Maria Nettis, Naghmeh Nikkheslat, Carmine Pariante, Karen Randall, Julia Schubert, Luca Sforzini, Hannah Sheridan, Camilla Simmons, Nisha Singh, Federico Turkheimer, Vicky Van Loo, Mattia Veronese, Marta Vicente Rodriguez, Toby Wood, Courtney Worrell, Zuzanna Zajkowska, Brian Campbell, Jan Egebjerg, Hans Eriksson, Francois Gastambide, Karen Husted Adams, Ross Jeggo, Thomas Moeller, Bob Nelson, Niels Plath, Christian Thomsen, Jan Torleif Pederson, Stevin Zorn, Catherine Deith, Scott Farmer, John McClean, Andrew McPherson, Nagore Penandes, Paul Scouller, Murray Sutherland, Mary Jane Attenburrow, Jithen Benjamin, Helen Jones, Fran Mada, Akintayo Oladejo, Katy Smith, Rita Balice-Gordon, Brendon Binneman, James Duerr, Terence Fullerton, Veeru Goli, Zoe Hughes, Justin Piro, Tarek Samad, Jonathan Sporn, Liz Hoskins, Charmaine Kohn, Lauren Wilcock, Franklin Aigbirhio, Junaid Bhatti, Ed Bullmore, Roido Manavaki, Sam Chamberlain, Marta Correia, Anna Crofts, Tim Fryer, Martin Graves, Alex Hatton, Manfred Kitzbichler, Mary-Ellen Lynall, Christina Maurice, Ciara O'Donnell, Linda Pointon, Peter St George Hyslop, Lorinda Turner, Petra Vertes, Barry Widmer, Guy Williams, Jonathan Cavanagh, Alison McColl, Robin Shaw, Erik Boddeke, Alison Baird, Stuart Clare, Phil Cowen, I-Shu (Dante) Huang, Sam Hurley, Simon Lovestone, Alejo Nevado-Holgado, Elena Ribe, Anviti Vyas, Laura Winchester, Madeleine Cleal, Diego Gomez-Nicola, Renzo Mancuso, Hugh Perry, Mara Cercignani, Charlotte Clarke, Alessandro Colasanti, Neil Harrison, Rosemary Murray, Jason O'Connor, Howard Mount.
Publisher Copyright:
© 2021 The Author(s)
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
KW - Choroid Plexus
KW - Depression
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85121986148&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2021.102926
DO - 10.1016/j.nicl.2021.102926
M3 - Article
AN - SCOPUS:85121986148
SN - 2213-1582
VL - 33
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102926
ER -