title: Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder.
abstract: BACKGROUND
  Frontal and temporal cortical thickness abnormalities have been observed in mood disorders. However, it is unknown whether cortical thickness abnormalities reflect early adverse effects of genetic and environmental risk factors predisposing to mood disorders or emerge at illness onset.
  
  
  METHODS
  Magnetic resonance imaging was conducted at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy control subjects (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Cortical surface reconstruction was applied to measure cortical thickness of frontal and temporal regions of interest. Mixed-effects models were used to investigate differences and longitudinal changes in cortical thickness.
  
  
  RESULTS
  Reduced cortical thickness in the right parahippocampal and fusiform gyrus across both time points was found in both high-risk groups. HR-MDD also had thinner parahippocampi than HR-well individuals. Over time, HR-well and HC individuals had progressive thickness reductions in the left inferior frontal and precentral gyrus, which were greater in HR-well subjects. HR-MDD showed left inferior frontal gyrus thickening relative to HR-well subjects and left precentral gyrus thickening relative to HR-well and HC individuals.
  
  
  CONCLUSIONS
  Reduced right parahippocampal and fusiform gyrus thickness are familial trait markers for vulnerability to mood disorders. Increased risk for mood disorders is associated with progressive cortical thinning in the left inferior frontal and precentral gyri in subjects who remain well. In contrast, onset of depression is associated with increasing left inferior frontal and precentral thickness.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.. Electronic address: Martina.Papmeyer@ed.ac.uk.
authors.forename: Martina
authors.initials: M
authors.lastname: Papmeyer
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Giles
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Sussmann
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Shauna
authors.initials: S
authors.lastname: Kielty
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D003865:Major Depressive Disorder / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005190:Family; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000235:genetics / Q000473:pathology*; D012307:Risk Factors; D013702:Temporal Lobe / Q000473:pathology; D055815:Young Adult
keywords: Bipolar disorder; Cortical thickness; High risk; Longitudinal; Magnetic resonance imaging; Major depressive disorder