Hippocampal volume and depression: a meta-analysis of MRI studies

Am J Psychiatry. 2004 Nov;161(11):1957-66. doi: 10.1176/appi.ajp.161.11.1957.


Objective: Several studies have found reduced hippocampal volume in patients with unipolar depression, but discrepancies exist. The authors performed a systematic review and meta-analysis of volumetric studies of the hippocampus in patients with mood disorders.

Method: Studies of hippocampal volume in unipolar and bipolar patients were identified. A meta-analysis of the 12 studies of unipolar depression fulfilling specific criteria was performed. The sample comprised 351 patients and 279 healthy subjects.

Results: The studies were highly heterogeneous regarding age and gender distribution, age at onset of the disorder, average number of episodes, and responsiveness to treatment, but the pooled effect size of depression was significant in both hemispheres for the unipolar patients. The weighted average showed a reduction of hippocampal volume of 8% on the left side and 10% on the right side. The causes of the heterogeneity were analyzed, and a meta-regression showed that the total number of depressive episodes was significantly correlated to right but not left hippocampal volume reduction.

Conclusions: Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder. Bipolar patients did not seem to show a reduction in hippocampal volume, but this has been much less investigated.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Bipolar Disorder / diagnosis
  • Depressive Disorder / diagnosis*
  • Female
  • Functional Laterality
  • Hippocampus / anatomy & histology*
  • Humans
  • Magnetic Resonance Imaging / statistics & numerical data*
  • Male
  • Middle Aged
  • Sex Factors