The Brain-Derived Neurotrophic Factor Val66Met Polymorphism, Hippocampal Volume, and Cognitive Function in Geriatric Depression

Objective: The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with geriatric depression. In studies of younger adults without depression, met allele carriers exhibit smaller hippocampal volumes and have poorer performance on neuropsychological tests. The authors examined the relationship between the BDNF gene and hippocampal volumes in depressed and nondepressed older individuals and its relationship with memory functions mediated by the hippocampus. Design: One hundred seventy-six elderly depressed white participants and 88 nondepressed participants completed clinical assessments, neuropsychological testing, and provided blood samples for genotyping. One hundred seventy-three participants also underwent brain magnetic resonance imaging. Statistical modeling tested the relationship between genotype and hippocampal volume and function while controlling for diagnosis and other covariates. Results: BDNF genotype was not associated with a difference in performance on tests mediated by the hippocampus, including word list learning, prose recall, nonverbal memory, or digit span. After controlling for covariates, BDNF genotype was not significantly associated with hippocampal volume (F([1, 171]) = 1.10, p = 0.30). Conclusion: Despite different findings in younger populations, the BDNF Val66Met polymorphism is not significantly associated with hippocampal volume or function in a geriatric population. The authors hypothesize that other factors may have a stronger effect on hippocampal structure in older individuals and that the association between the Val66Met polymorphism and geriatric depression is mediated through other mechanisms. (Am J Geriatr Psychiatry 2010; 18:323-331)