title: White matter integrity in individuals at high genetic risk of bipolar disorder.
abstract: BACKGROUND
  Bipolar disorder is a familial psychiatric disorder associated with reduced white matter integrity, but it is not clear whether such abnormalities are present in young unaffected relatives and, if so, whether they have behavioral correlates. We investigated with whole brain diffusion tensor imaging whether increased genetic risk for bipolar disorder is associated with reductions in white matter integrity and whether these reductions are associated with cyclothymic temperament.
  
  
  METHODS
  Diffusion tensor imaging data of 117 healthy unaffected relatives of patients with bipolar disorder and 79 control subjects were acquired. Cyclothymic temperament was measured with the cyclothymia scale of the Temperament Evaluation of Memphis, Pisa and San Diego auto-questionnaire. Voxel-wise between-group comparisons of fractional anisotropy (FA) and regression of cyclothymic temperament were performed with tract-based spatial statistics.
  
  
  RESULTS
  Compared to the control group, unaffected relatives had reduced FA in one large widespread cluster. Cyclothymic temperament was inversely related to FA in the internal capsules bilaterally and in left temporal white matter, regions also found to be reduced in high-risk subjects.
  
  
  CONCLUSIONS
  These results show that widespread white matter integrity reductions are present in unaffected relatives of bipolar patients and that more localized reductions might underpin cyclothymic temperament. These findings suggest that white matter integrity is an endophenotype for bipolar disorder with important behavioral associations previously linked to the etiology of the condition.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, United Kingdom. e.sprooten@sms.ed.ac.uk
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.forename: Jessika E
authors.initials: JE
authors.lastname: Sussmann
authors.forename: April
authors.initials: A
authors.lastname: Clugston
authors.forename: Anna
authors.initials: A
authors.lastname: Peel
authors.forename: James
authors.initials: J
authors.lastname: McKirdy
authors.forename: T William J
authors.initials: TW
authors.lastname: Moorhead
authors.forename: Seonaid
authors.initials: S
authors.lastname: Anderson
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Shand
authors.forename: Stephen
authors.initials: S
authors.lastname: Giles
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.forename: Eve C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003337:Corpus Callosum / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D020772:Internal Capsule / Q000473:pathology; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D013694:Temperament; D055815:Young Adult