title: Sub-threshold depressive symptoms and brain structure: A magnetic resonance imaging study within the Whitehall II cohort.
abstract: Late-life sub-threshold depressive symptoms (i.e. depressive symptoms that do not meet the criteria for a diagnosis of major depressive disorder) are associated with impaired physical health and function, and increased risk of major depressive disorder. Magnetic resonance imaging (MRI) studies examining late-life major depressive disorder find structural brain changes in grey and white matter. However, the extent to which late-life sub-threshold depression is associated with similar hallmarks is not well established.
  
  
  
  Participants with no history of major depressive disorder were selected from the Whitehall Imaging Sub-Study (n=358, mean age 69±5 years, 17% female). Depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale (CES-D) at three previous Whitehall II Study phases (2003-04, 2007-09 and 2012-13) and at the time of the MRI scan (2012-14). The relationships between current and cumulative depressive symptoms and MRI brain measures were explored using Voxel-Based Morphometry (VBM) for grey matter and Tract Based Spatial Statistics (TBSS) for white matter.
  
  
  
  Current sub-threshold depressive symptoms were associated with significant reductions in fractional anisotropy and increases in axial and radial diffusivity. There were no significant relationships between current depressive symptoms and grey matter measures, or cumulative depressive symptoms and MRI measures.
  
  
  
  The prevalence (10%) of sub-threshold depressive symptoms means that analyses may be underpowered to detect subtle differences in brain structure.
  
  
  
  Current sub-threshold depressive symptoms are associated with changes in white matter microstructure, indicating that even mild depressive symptoms are associated with similar MRI hallmarks to those in major depressive disorder.
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom. Electronic address: Charlotte.allan@ntw.nhs.uk.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Allan
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Sexton
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Anya
authors.initials: A
authors.lastname: Topiwala
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Abda
authors.initials: A
authors.lastname: Mahmood
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Enikő
authors.initials: E
authors.lastname: Zsoldos
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shipley
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, OX3 7JX, United Kingdom.
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Ebmeier
mesh_terms: D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D015331:Cohort Studies; D003863:Depression / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: Brain; Depression; Grey matter; Magnetic resonance imaging; White matter