Paola Magioncalda1, Matteo Martino2, Samuele Tardito3, Bruno Sterlini4, Benedetta Conio5, Valentina Marozzi6, Giulia Adavastro7, Laura Capobianco8, Daniel Russo9, Alessia Parodi10, Francesca Kalli11, Giorgia Nasi12, Tiziana Altosole13, Niccolò Piaggio14, Georg Northoff15, Daniela Fenoglio16, Matilde Inglese17, Gilberto Filaci18, Mario Amore19. 1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: paola.magioncalda@gmail.com. 2. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: matteomartino9@gmail.com. 3. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: tarditosamuele.hrd@gmail.com. 4. Department of Experimental Medicine, University of Genoa, Genoa, Italy; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genoa, Italy. Electronic address: bruno.sterlini@unige.it. 5. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: benedetta.conio@hotmail.it. 6. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: valeviaggia@hotmail.com. 7. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: siriogiulia@libero.it. 8. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: laura.capobianco3@gmail.com. 9. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: daniel_russo@hotmail.it. 10. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: alessiaparodi@yahoo.it. 11. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: francesca.kalli@gmail.com. 12. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: giorgiaenne@gmail.com. 13. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: tiziana.alto@gmail.com. 14. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Neurology, University of Genoa, Genoa, Italy. Electronic address: aaa_sj86@yahoo.it. 15. University of Ottawa Brain and Mind Research Institute, and Mind Brain Imaging and Neuroethics Royal's Institute of Mental Health Research, University of Ottawa, Ottawa, Canada; Centre for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, China; TMU Research Center for Brain and Consciousness, Taipei, Taiwan. Electronic address: georg.northoff@theroyal.ca. 16. IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy. Electronic address: daniela.fenoglio@unige.it. 17. IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Neurology, University of Genoa, Genoa, Italy; Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, NY, USA. Electronic address: matilde.inglese@mssm.edu. 18. IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy. Electronic address: gfilaci@unige.it. 19. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: mario.amore@unige.it.
Abstract
BACKGROUND: White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. METHOD: In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. RESULTS: We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. CONCLUSIONS: Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD.
BACKGROUND:White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. METHOD: In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. RESULTS: We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. CONCLUSIONS: Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD.
Authors: Ana Catarina Pereira; Jessica De Pascale; Rosa Resende; Susana Cardoso; Isabel Ferreira; Bruno Miguel Neves; Mylène A Carrascal; Mónica Zuzarte; Nuno Madeira; Sofia Morais; António Macedo; Anália do Carmo; Paula I Moreira; Maria Teresa Cruz; Cláudia F Pereira Journal: Cell Mol Life Sci Date: 2022-03-28 Impact factor: 9.261
Authors: Teodor T Postolache; Deborah R Medoff; Clayton H Brown; Li Juan Fang; Sanjaya K Upadhyaya; Christopher A Lowry; Michael Miller; Julie A Kreyenbuhl Journal: Pteridines Date: 2021-09-23 Impact factor: 0.581