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

From the Center for Human Genetics (SZ, MCS), the Neuropsychiatric Imaging Research Laboratory (WDT, MEP, JRM, KRRK), and the Departments of Medicine (MCS), Psychiatry (WDT, DRM, MEP, DCS, KRRK), and Radiology (JRM), Duke University Medical Center, Durham, NC; The Miami Institute of Human Genomics (SZ), University of Miami Miller School of Medicine, Miami, FL; and Duke–NUS Graduate Medical School (KRRK), Singapore.

Address correspondence and reprint requests to: Warren D. Taylor, M.D., E-mail: Taylo066{at}mc.duke.edu.

	Abstract

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 (F_1,311 = 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 (F_1,311 = 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.

Key Words: genetic polymorphisms, magnetic resonance imaging, depression