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

doi:10.1016/j.bbi.2018.04.017

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 Behav Immun. 2018 Oct:73:192-204. doi: 10.1016/j.bbi.2018.04.017. Epub 2018 May 1.

Authors

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

Affiliations

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.

PMID: 29723656
DOI: 10.1016/j.bbi.2018.04.017

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.

Keywords: Bipolar disorder; Immunological alterations; Mania; T cells; TBSS; White matter abnormalities.

MeSH terms

Adult
Anisotropy
Bipolar Disorder / physiopathology*
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / physiology
Corpus Callosum / diagnostic imaging
Diffusion Magnetic Resonance Imaging / methods
Diffusion Tensor Imaging / methods
Female
Humans
Male
Middle Aged
White Matter / immunology*
White Matter / physiology
White Matter / ultrastructure*