title: The neural basis of familial risk and temperamental variation in individuals at high risk of bipolar disorder.
abstract: BACKGROUND
  Bipolar disorder is a highly heritable psychiatric disorder characterized by episodic elevation or depression of mood. Bipolar disorder is associated with structural and functional brain abnormalities but it is unclear whether these are present in relatives of affected individuals and if they are associated with subclinical symptoms or traits associated with the disorder.
  
  
  METHODS
  Functional magnetic resonance imaging scans were conducted on 93 unrelated relatives of bipolar disorder patients and 70 healthy comparison subjects performing the Hayling sentence completion paradigm. Examination of comparison subjects versus high-risk individuals was followed by assessments of associations with depression scores and measures of cyclothymic temperament.
  
  
  RESULTS
  Examination of comparison subjects versus high-risk subjects revealed increased activation in the high-risk group in the left amygdala. No interaction effects were observed between the groups for scores of depression or cyclothymia and activation in any region. Significant associations were found across the groups with depression ratings and activation in the ventral striatum and with cyclothymia and activation in ventral prefrontal regions, however no interaction effects were observed between the groups.
  
  
  CONCLUSIONS
  Differences in activation in the left amygdala in those at familial risk may represent a heritable endophenotype of bipolar disorder. Activation in striatal and ventral prefrontal regions may, in contrast, represent a distinct biological basis of subclinical features of the illness regardless of the presence of familial risk.
authors: Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, Scotland, United Kingdom. heather.whalley@ed.ac.uk
authors: Heather C
authors: HC
authors: Whalley
authors: Jessika E
authors: JE
authors: Sussmann
authors: Goultchira
authors: G
authors: Chakirova
authors: Prerona
authors: P
authors: Mukerjee
authors: Anna
authors: A
authors: Peel
authors: James
authors: J
authors: McKirdy
authors: Jeremy
authors: J
authors: Hall
authors: Eve C
authors: EC
authors: Johnstone
authors: Stephen M
authors: SM
authors: Lawrie
authors: Andrew M
authors: AM
authors: McIntosh