title: Reduced white matter integrity in sibling pairs discordant for bipolar disorder.
abstract: OBJECTIVE
  Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects.
  
  
  METHODS
  The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional anisotropy from 10 regions of interest. Additionally, intraclass correlation coefficients were calculated between the sibling pairs as an index of familiality.
  
  
  RESULTS
  Widespread fractional anisotropy reductions in bipolar patients (>40,000 voxels) and more subtle reductions in their siblings, mainly restricted to the corpus callosum, posterior thalamic radiations, and left superior longitudinal fasciculus (>2,000 voxels) were observed. Similarly, region-of-interest analysis revealed significant reductions in most white matter regions in patients. In siblings, fractional anisotropy in the posterior thalamic radiation and the forceps was nominally reduced. Significant between-sibling correlations were found for mean fractional anisotropy across the tract-based spatial statistic skeleton, within significant clusters, and within nearly all regions of interest.
  
  
  CONCLUSIONS
  These findings emphasize the relevance of white matter to neuropathology and familiality of bipolar disorder and encourage further use of white matter integrity markers as endophenotypes in genetic studies.
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Brumbaugh
authors.forename: Emma E M
authors.initials: EE
authors.lastname: Knowles
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.forename: John
authors.initials: J
authors.lastname: Lewis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barrett
authors.forename: Stefanie
authors.initials: S
authors.lastname: Landau
authors.forename: Lindsay
authors.initials: L
authors.lastname: Cyr
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Winkler
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D059906:Neuroimaging; D011569:Psychiatric Status Rating Scales; D035781:Siblings / Q000523:psychology