title: White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study.
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.
  
  
  METHODS
  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.
authors.affiliation: Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology,University Hospitals Leuven,Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry,King's College London,UK.
authors.forename: C
authors.initials: C
authors.lastname: Chaddock
authors.affiliation: Clinical Science Institute,National University of Ireland,Galway,Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Forde
authors.affiliation: icoMetrix NV, Leuven,Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Van Hecke
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry,King's College London,UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Image Sciences Institute,University Medical Centre Utrecht,The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology,University Hospitals Leuven,Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Sunaert
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry,King's College London,UK.
authors.forename: M
authors.initials: M
authors.lastname: Walshe
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry,King's College London,UK.
authors.forename: E
authors.initials: E
authors.lastname: Bramon
authors.affiliation: Clinical Science Institute,National University of Ireland,Galway,Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Cannon
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry,King's College London,UK.
authors.forename: R
authors.initials: R
authors.lastname: Murray
authors.affiliation: Clinical Science Institute,National University of Ireland,Galway,Ireland.
authors.forename: C
authors.initials: C
authors.lastname: McDonald
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D058068:Endophenotypes; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D066127:White Matter / Q000473:pathology*; D055815:Young Adult