title: Altered development of white matter in youth at high familial risk for bipolar disorder: a diffusion tensor imaging study.
abstract: OBJECTIVE
  To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy offspring having a parent with BD were compared with those in healthy controls.
  
  
  METHODS
  A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity were examined using whole-brain analyses, co-varying for age.
  
  
  RESULTS
  Group-by-age interactions showed a linear increase in FA and a linear decrease in RD in CONT in the left corpus callosum and right inferior longitudinal fasciculus. In HBO, there was a linear decrease in FA and an increase in RD with age in the left corpus callosum and no relation between FA or RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed linear and showed nonlinear relations between FA and RD and age in these regions in CONT and HBO.
  
  
  CONCLUSIONS
  This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO compared with CONT in the corpus callosum and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.forename: Cecile D
authors.initials: CD
authors.lastname: Ladouceur
authors.forename: Soledad
authors.initials: S
authors.lastname: Romero
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.forename: David A
authors.initials: DA
authors.lastname: Axelson
authors.forename: David J
authors.initials: DJ
authors.lastname: Kupfer
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002648:Child; D003337:Corpus Callosum / Q000473:pathology; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D012016:Reference Values; D012307:Risk Factors; D013702:Temporal Lobe / Q000473:pathology; D014793:Visual Cortex / Q000502:physiology