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Controlled Clinical Trial
. 2010 Sep;125(1-3):262-8.
doi: 10.1016/j.jad.2010.02.115. Epub 2010 Mar 25.

BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression

George S Alexopoulos  1 , Charles E Glatt, Matthew J Hoptman, Dora Kanellopoulos, Christopher F Murphy, Robert E Kelly Jr, Sarah S Morimoto, Kelvin O Lim, Faith M Gunning
Affiliations
Controlled Clinical Trial

BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression

George S Alexopoulos et al. J Affect Disord. 2010 Sep.

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 BDNF(val/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: BDNF(met) carriers were more likely to achieve remission than BDNF(val/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 BDNF(val66met) status and microstructural abnormalities in predicting remission.

Limitations: Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose.

Conclusions: Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/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.

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Figures

Figure 1
Figure 1
Left superior corona radiata ROI (Fig 1a). Right inferior longitudinal fasciculus ROI (Fig 1b) as estimated by ROQS. Images are in radiological view.
See this image and copyright information in PMC

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