Hippocampal volumes and the brain-derived neurotrophic factor val66met polymorphism in geriatric major depression

Dora Kanellopoulos, Faith M. Gunning, Sarah S. Morimoto, Matthew J. Hoptman, Christopher F. Murphy, Robert E. Kelly, Charles Glatt, Kelvin O. Lim, George S. Alexopoulos

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Objectives: Structural abnormalities in the hippocampus have been implicated in the pathophysiology of major depressive disorder (MDD). The brain-derived neurotrophic factor (BDNF) val66met polymorphism may contribute to these abnormalities and therefore confer vulnerability to MDD. This study examined whether there is a relationship among BDNF genotype, hippocampal volumes, and MDD in older adults. Methods: Thirty-three older adults with MDD and 23 psychiatrically normal comparison subjects were studied. Structural magnetic resonance imaging analysis was used to quantify hippocampal volumes. A repeated-measures analysis of covariance examined the relationships among BDNF val66met (val/val, met carrier), diagnosis (depressed, nondepressed), and hippocampal volumes (right, left). Age, gender, education, and whole brain volume were included as covariates. Results: Elderly MDD BDNF val/val homozygotes had significantly higher right hippocampal volumes compared with nondepressed val/val subjects. However, there was no difference between the depressed and healthy nondepressed met carriers. In addition, depressed met carriers had an earlier age of onset of depressive illness than val/val homozygotes, but age of onset did not moderate the relationship between hippocampal volumes and MDD diagnosis. Conclusion: These results provide preliminary evidence of a neuroprotective role of the val/val genotype, suggesting that neurotrophic factor production protects against pathophysiological processes triggered by depression in older adults with later age of onset of MDD. The BDNF val66met polymorphism may play a salient role in structural alterations of the hippocampus in older adults with MDD.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalAmerican Journal of Geriatric Psychiatry
Issue number1
StatePublished - Jan 2011

Bibliographical note

Funding Information:
Personnel and imaging cost of this work was supported by NIMH grants R01 MH65653, P030 MH085943,. T32 MH019132 (to GSA), K23 MH067702 (to CFM), K23 MH74818 (to FGD), the Sanchez Foundation, and TRU Foundation. Escitalopram and placebo were provided free of cost by Forest Pharmaceuticals, Inc.


  • BDNF val66met
  • Geriatric depression
  • hippocampus
  • older adults


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