title: Prediction of depression in individuals at high familial risk of mood disorders using functional magnetic resonance imaging.
abstract: OBJECTIVE
  Bipolar disorder is a highly heritable condition. First-degree relatives of affected individuals have a more than a ten-fold increased risk of developing bipolar disorder (BD), and a three-fold risk of developing major depressive disorder (MDD) than the general population. It is unclear however whether differences in brain activation reported in BD and MDD are present before the onset of illness.
  
  
  METHODS
  We studied 98 young unaffected individuals at high familial risk of BD and 58 healthy controls using functional Magnetic Resonance Imaging (fMRI) scans and a task involving executive and language processing. Twenty of the high-risk subjects subsequently developed MDD after the baseline fMRI scan.
  
  
  RESULTS
  At baseline the high-risk subjects who later developed MDD demonstrated relatively increased activation in the insula cortex, compared to controls and high risk subjects who remained well. In the healthy controls and high-risk group who remained well, this region demonstrated reduced engagement with increasing task difficulty. The high risk subjects who subsequently developed MDD did not demonstrate this normal disengagement. Activation in this region correlated positively with measures of cyclothymia and neuroticism at baseline, but not with measures of depression.
  
  
  CONCLUSIONS
  These results suggest that increased activation of the insula can differentiate individuals at high-risk of bipolar disorder who later develop MDD from healthy controls and those at familial risk who remain well. These findings offer the potential of future risk stratification in individuals at risk of mood disorder for familial reasons.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. heather.whalley@ed.ac.uk
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.forename: Jessika E
authors.initials: JE
authors.lastname: Sussmann
authors.forename: Liana
authors.initials: L
authors.lastname: Romaniuk
authors.forename: Tiffany
authors.initials: T
authors.lastname: Stewart
authors.forename: Martina
authors.initials: M
authors.lastname: Papmeyer
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.forename: Suzanna
authors.initials: S
authors.lastname: Hackett
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D001519:Behavior; D001931:Brain Mapping; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D003863:Depression / Q000209:etiology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019964:Mood Disorders / Q000150:complications* / Q000503:physiopathology*; D011379:Prognosis; D019655:Quantitative Trait, Heritable; D012372:ROC Curve; D012307:Risk Factors; D013647:Task Performance and Analysis; D013694:Temperament; D055815:Young Adult