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White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study

Published online by Cambridge University Press:  26 November 2013

L. Emsell ,
C. Chaddock ,
N. Forde ,
W. Van Hecke ,
G. J. Barker ,
A. Leemans ,
S. Sunaert ,
M. Walshe ,
E. Bramon  and
D. Cannon
...Show all authors
L. Emsell*
Affiliation:
Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology, University Hospitals Leuven, Belgium Clinical Science Institute, National University of Ireland, Galway, Ireland
C. Chaddock
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
N. Forde
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
W. Van Hecke
Affiliation:
icoMetrix NV, Leuven, Belgium
G. J. Barker
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, King's College London, UK
A. Leemans
Affiliation:
Image Sciences Institute, University Medical Centre Utrecht, The Netherlands
S. Sunaert
Affiliation:
Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology, University Hospitals Leuven, Belgium
M. Walshe
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
E. Bramon
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
D. Cannon
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
R. Murray
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
C. McDonald
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
*
*Address for correspondence: Dr L. Emsell, Ph.D., Medical Imaging Research Centre, Department of Radiology, University Hospital Leuven, Herestraat 49 bus 7003, 3000 Leuven, Belgium. (Email: [email protected])
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Abstract

Background

White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.

Method

Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.

Results

We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.

Conclusions

WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.

Keywords

Bipolar disorderdiffusion tensor imagingendophenotypesgenetic riskwhite matter
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 10 , July 2014 , pp. 2139 - 2150
Copyright
Copyright © Cambridge University Press 2013 

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