Sub-threshold depressive symptoms and brain structure: A magnetic resonance imaging study within the Whitehall II cohort

Abstract

Background: 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.

Methods: 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.

Results: 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.

Limitations: The prevalence (10%) of sub-threshold depressive symptoms means that analyses may be underpowered to detect subtle differences in brain structure.

Conclusions: 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.

Keywords: Brain; Depression; Grey matter; Magnetic resonance imaging; White matter.

Fig. 1

Attrition of participants.

Fig. 2

Localisation of group differences in DTI measures between CES-D≤10 and CES-D>10 groups. Voxels displaying a significant reduction in FA (red), increase in AD (yellow) and increase in RD (blue) in the sub-threshold depression group, dilated for illustrative purposes, are overlaid on a green skeleton. Age, sex, education and MoCA scores were included as covariates. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)