Altered hippocampal function in major depression despite intact structure and resting perfusion

A. Finkelmeyer (Lead Author), J. Nilsson, J. He, L. Stevens, J.J. Maller, R. A. Moss, S. Small, P. Gallagher, K. Coventry, I.N. Ferrier, R. H. McAllister-Williams

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Background: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.

Method: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.

Results: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.

Conclusions: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.
Original languageEnglish
Pages (from-to)2157-2168
Number of pages12
JournalPsychological Medicine
Issue number10
Early online date19 May 2016
Publication statusPublished - Jul 2016


  • Hippocampus
  • magnetic resonance imaging
  • major depressive disorder
  • spatial memory

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