Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness

Abstract

Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss.

Figure 1

Scatter‐plots of associations between total hippocampal volume (mL) and behavioral measures, NEO‐FFI neuroticism and DASS‐21 depression and stress, within BDNF Met carriers and Val/Val homozygotes.

Figure 2

Line graphs depicting estimated marginal means from the multiple regression analysis, in which the interaction of BDNF Val66Met genotype status and DASS‐21 level of depression predicted grey matter volume for the left and right hippocampus. BDNF Met carriers (grey line) with higher depression scores showed reduced hippocampal volume compared with Val/Val genotypes (black line) with similarly high depression scores.