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A multicentric multimodal in vivo microscopy MRI study of bipolar disorder reveals axonal loss and demyelination

Published online by Cambridge University Press:  01 September 2022

S. Sarrazin*
Affiliation:
MSP PASTEUR, -, CHEVILLY LARUE, France
C. Poupon
Affiliation:
CEA Saclay, Neurospin, Gif sur Yvette, France
I. Uszynski
Affiliation:
CEA Saclay, Neurospin, Gif sur Yvette, France
J.-F. Mangin
Affiliation:
CEA Saclay, Neurospin, Gif sur Yvette, France
M. Polosan
Affiliation:
GIN, Inserm U836, Grenoble, France
P. Favre
Affiliation:
CEA Saclay, Neurospin, Gif sur Yvette, France
C. Laidi
Affiliation:
APHP CHU Mondor, Psychiatrie, Créteil, France
M.-A. D’Albis
Affiliation:
APHP CHU Mondor, Psychiatrie, Créteil, France
M. Leboyer
Affiliation:
APHP CHU Mondor, Psychiatrie, Créteil, France
P.-M. Lledo
Affiliation:
Institut Pasteur, Unité Perception Et Mémoire, Paris, France
C. Henry
Affiliation:
Institut Pasteur, Unité Perception Et Mémoire, Paris, France
L. Emsell
Affiliation:
KU Leuven, Translational Neuropsychiatry, Leuven, Belgium
M. Shakeel
Affiliation:
Hotchkiss Brain Institute, Department Of Psychiatry, Calgary, Canada
V. Goghari
Affiliation:
University of Toronto Scarborough, Graduate Department Of Psychological Clinical Science, Toronto, Canada
J. Houenou
Affiliation:
APHP CHU Mondor, Psychiatrie, Créteil, France
*
*Corresponding author.

Abstract

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Introduction

Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown.

Objectives

Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls.

Methods

77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness.

Results

We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus.

Conclusions

We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI.

Disclosure

No significant relationships.

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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