title: Structural brain network analysis in families multiply affected with bipolar I disorder.
abstract: Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives.
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; Department of Psychiatry, University Medical Centre Groningen, The Netherlands. Electronic address: j.n.forde@umcg.nl.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Forde
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Stefani
authors.initials: S
authors.lastname: O'Donoghue
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Scanlon
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; Translational MRI, Department of Imaging & Pathology, KU Leuven & Radiology, University Hospitals Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Chaddock
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: iMinds-Vision Lab, University of Antwerp, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Jeurissen
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D055815:Young Adult
keywords: Diffusion-weighted MRI; Endophenotype; Familial bipolar disorder; Network analysis