BDNF Val66met polymorphism, white matter abnormalities and remission of geriatric depression

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

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Objective: The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNFval/met status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. Method: Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. Results: BDNFmet carriers were more likely to achieve remission than BDNFval/val homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNFval66met status and microstructural abnormalities in predicting remission. Limitations: Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. Conclusions: Depressed older BDNFmet carriers had a higher remission rate than BDNFval/val homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF val66met and remission is due to different effects of BDNF in brain structures related to mood regulation.

Original languageEnglish (US)
Pages (from-to)262-268
Number of pages7
JournalJournal of Affective Disorders
Volume125
Issue number1-3
DOIs
StatePublished - Sep 2010

Bibliographical note

Funding Information:
Personnel and imaging cost of this work was supported by NIMH grants R01 MH079414 , R01 MH065653 , P030 MH085943 , T32 MH019132 (GSA), K23 MH067702 (CFM), and K23 MH074818 (FGD), the Sanchez Foundation , and TRU Foundation . Escitalopram and placebo were provided free of cost by Forest Pharmaceuticals, Inc .

Keywords

  • BDNF val66met
  • Geriatric depression
  • Remission
  • White matter abnormalities

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