Objective: The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been linked to unipolar major depressive disorder (MDD) and magnetic resonance imaging (MRI) hyperintensities. The authors examined the relationship between the MTHFR C677T polymorphism (C677T) and a) geriatric depression, b) MRI hyperintense lesion volume, and c) neurocognitive test performance.
Design: Cross-sectional.
Setting: Duke University Medical Center.
Participants: Depressed (N = 178) and comparison (N = 85) elderly subjects.
Measurements: Subjects had blood drawn to assess MTHFR genotype, were imaged by MRI to determine their white matter hyperintense lesion (WML) and gray matter hyperintense lesion (GML) volume, and assessed using a comprehensive neurocognitive battery evaluating multiple domains of function. Linear regression models were fit to test the effect of genotype, a depression by genotype interaction, and an age by genotype interaction on both hyperintense lesion volume measures and neurocognitive task performance.
Results: The MTHFR C677T genotype by age interaction term was significantly associated with MRI WML volume (p = 0.0175); however, this relationship was no longer statistically significant when WML volumes underwent a log transformation to produce a more normal distribution. The 677T allele was neither more frequent in depressed subjects nor associated with either gray matter hyperintensity volume or neurocognitive test performance.
Conclusions: MTHFR genotype affects the relationship between age and WML volume where individuals who carry the 677T allele exhibit greater WML volume by age, although this relationship should be verified given the failure to replicate the finding using transformed WML volumes. Genotype was not related to GML volume, cognitive function, or presence of depression, although demographic differences could account for this negative finding.