The Brain-Derived Neurotrophic Factor VAL66MET Polymorphism and Cerebral White Matter Hyperintensities in Late-Life Depression

Objective In animal models, brain-derived neurotrophic factor (BDNF) appears to protect against cerebral ischemia. The authors examined whether the BDNF Val66Met polymorphism, which affects BDNF distribution, was associated with greater volumes of hyperintense lesions as detected on magnetic resonan...

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Published in:The American journal of geriatric psychiatry 2008-04, Vol.16 (4), p.263-271
Main Authors: Taylor, Warren D., M.D, Züchner, Stephan, M.D, McQuoid, Douglas R., B.S, Payne, Martha E., Ph.D, MacFall, James R., Ph.D, Steffens, David C., M.D., M.H.S, Speer, Marcy C., Ph.D, Krishnan, K Ranga R., M.D
Format: Article
Language:English
Subjects:
Age of Onset
Aged
Amino Acid Substitution
Brain - pathology
Brain-Derived Neurotrophic Factor - genetics
Cross-Sectional Studies
depression
Depression - genetics
Depression - pathology
Female
genetic polymorphisms
Genotype
Humans
Internal Medicine
magnetic resonance imaging
Magnetic Resonance Imaging - methods
Male
Methionine
Polymorphism, Single Nucleotide
Valine
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Summary:Objective In animal models, brain-derived neurotrophic factor (BDNF) appears to protect against cerebral ischemia. The authors examined whether the BDNF Val66Met polymorphism, which affects BDNF distribution, was associated with greater volumes of hyperintense lesions as detected on magnetic resonance imaging in a cohort of depressed and nondepressed elders. Design Subjects completed cross-sectional assessments, including clinical evaluation and a brain magnetic resonance imaging scan, and provided blood samples for Val66Met genotyping. Setting The study was conducted at a university-based academic hospital. Participants Participants included 199 depressed and 113 nondepressed subjects aged 60 years or older. Measurement Hyperintensity lesion volumes were measured using a semiautomated segmentation procedure. Statistical models examined the relationship between genotype and lesion volume while controlling for depression, presence of hypertension, age, and sex. Results After controlling for covariates, Met66 allele carriers exhibited significantly greater white matter hyperintensity volumes (F1,311 = 4.09, p = 0.0442). This effect was independent of a diagnosis of depression or report of hypertension. Genotype was not significantly related to gray matter hyperintensity volume (F1,311 = 1.14, p = 0.2871). Conclusions The BDNF Met66 allele is associated with greater white matter hyperintensity volumes in older individuals. Further work is needed to determine how this may be associated with other clinically relevant findings in late-life depression.
ISSN:1064-7481
1545-7214
DOI:10.1097/JGP.0b013e3181591c30