White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania

Combined DTI and immunological investigation in the different phases of bipolar disorder

Paola Magioncalda, Matteo Martino, Samuele Tardito, Bruno Sterlini, Benedetta Conio, Valentina Marozzi, Giulia Adavastro, Laura Capobianco, Daniel Russo, Alessia Parodi, Francesca Kalli, Giorgia Nasi, Tiziana Altosole, Niccolò Piaggio, Georg Northoff, Daniela Fenoglio, Matilde Inglese, Gilberto Filaci, Mario Amore

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)192-204
Number of pages13
JournalBrain, Behavior, and Immunity
Volume73
DOIs
Publication statusPublished - Oct 1 2018
Externally publishedYes

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Diffusion Tensor Imaging
Bipolar Disorder
T-Lymphocytes
Anisotropy
Corpus Callosum
White Matter
Cytokines

Keywords

  • Bipolar disorder
  • Immunological alterations
  • Mania
  • T cells
  • TBSS
  • White matter abnormalities

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania : Combined DTI and immunological investigation in the different phases of bipolar disorder. / Magioncalda, Paola; Martino, Matteo; Tardito, Samuele; Sterlini, Bruno; Conio, Benedetta; Marozzi, Valentina; Adavastro, Giulia; Capobianco, Laura; Russo, Daniel; Parodi, Alessia; Kalli, Francesca; Nasi, Giorgia; Altosole, Tiziana; Piaggio, Niccolò; Northoff, Georg; Fenoglio, Daniela; Inglese, Matilde; Filaci, Gilberto; Amore, Mario.

In: Brain, Behavior, and Immunity, Vol. 73, 01.10.2018, p. 192-204.

Research output: Contribution to journalArticle

Magioncalda, P, Martino, M, Tardito, S, Sterlini, B, Conio, B, Marozzi, V, Adavastro, G, Capobianco, L, Russo, D, Parodi, A, Kalli, F, Nasi, G, Altosole, T, Piaggio, N, Northoff, G, Fenoglio, D, Inglese, M, Filaci, G & Amore, M 2018, 'White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder', Brain, Behavior, and Immunity, vol. 73, pp. 192-204. https://doi.org/10.1016/j.bbi.2018.04.017
Magioncalda, Paola ; Martino, Matteo ; Tardito, Samuele ; Sterlini, Bruno ; Conio, Benedetta ; Marozzi, Valentina ; Adavastro, Giulia ; Capobianco, Laura ; Russo, Daniel ; Parodi, Alessia ; Kalli, Francesca ; Nasi, Giorgia ; Altosole, Tiziana ; Piaggio, Niccolò ; Northoff, Georg ; Fenoglio, Daniela ; Inglese, Matilde ; Filaci, Gilberto ; Amore, Mario. / White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania : Combined DTI and immunological investigation in the different phases of bipolar disorder. In: Brain, Behavior, and Immunity. 2018 ; Vol. 73. pp. 192-204.
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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.",
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T1 - White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania

T2 - Combined DTI and immunological investigation in the different phases of bipolar disorder

AU - Magioncalda, Paola

AU - Martino, Matteo

AU - Tardito, Samuele

AU - Sterlini, Bruno

AU - Conio, Benedetta

AU - Marozzi, Valentina

AU - Adavastro, Giulia

AU - Capobianco, Laura

AU - Russo, Daniel

AU - Parodi, Alessia

AU - Kalli, Francesca

AU - Nasi, Giorgia

AU - Altosole, Tiziana

AU - Piaggio, Niccolò

AU - Northoff, Georg

AU - Fenoglio, Daniela

AU - Inglese, Matilde

AU - Filaci, Gilberto

AU - Amore, Mario

PY - 2018/10/1

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N2 - 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.

AB - 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.

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KW - TBSS

KW - White matter abnormalities

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