Brain grey matter volume alterations in late-life depression

J Psychiatry Neurosci. 2014 Nov;39(6):397-406. doi: 10.1503/jpn.130275.


Background: Voxel-based morphometry (VBM) studies have demonstrated that grey matter abnormalities are involved in the pathophysiology of late-life depression (LLD), but the findings are inconsistent and have not been quantitatively reviewed. The aim of the present study was to conduct a meta-analysis that integrated the reported VBM studies, to determine consistent grey matter alterations in individuals with LLD.

Methods: A systematic search was conducted to identify VBM studies that compared patients with LLD and healthy controls. We performed a meta-analysis using the effect size signed differential mapping method to quantitatively estimate regional grey matter abnormalities in patients with LLD.

Results: We included 9 studies with 11 data sets comprising 292 patients with LLD and 278 healthy controls in our meta-analysis. The pooled and subgroup meta-analyses showed robust grey matter reductions in the right lentiform nucleus extending into the parahippocampus, the hippocampus and the amygdala, the bilateral medial frontal gyrus and the right subcallosal gyrus as well as a grey matter increase in the right lingual gyrus. Meta-regression analyses showed that mean age and the percentage of female patients with LLD were not significantly related to grey matter changes.

Limitations: The analysis techniques, patient characteristics and clinical variables of the studies included were heterogeneous, and most participants were medicated.

Conclusion: The present meta-analysis is, to our knowledge, the first to overcome previous inconsistencies in the VBM studies of LLD and provide robust evidence for grey matter alterations within fronto-striatal-limbic networks, thereby implicating them in the pathophysiology of LLD. The mean age and the percentage of female patients with LLD did not appear to have a measurable impact on grey matter changes, although we cannot rule out the contributory effects of medication.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Brain / pathology*
  • Depressive Disorder / pathology*
  • Gray Matter / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging
  • Organ Size
  • Regression Analysis