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 resonance imaging in a cohort of depressed and nondepressed elders.


METHODS
Subjects completed cross-sectional assessments, including clinical evaluation and a brain magnetic resonance imaging scan, and provided blood samples for Val66Met genotyping.


METHODS
The study was conducted at a university-based academic hospital.


METHODS
Participants included 199 depressed and 113 nondepressed subjects aged 60 years or older.


METHODS
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.
Taylor
Warren D
WD
Neuropsychiatric Imaging Research Laboratory, and the Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. Taylo066@mc.duke.edu
Züchner
Stephan
S
McQuoid
Douglas R
DR
Payne
Martha E
ME
MacFall
James R
JR
Steffens
David C
DC
Speer
Marcy C
MC
Krishnan
K Ranga R
KR
D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003430:Cross-Sectional Studies; D003863:Depression / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008715:Methionine; D020641:Polymorphism, Single Nucleotide; D014633:Valine
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine