The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology

Abstract

A variation in the BDNF gene (val66met) affects the function of BDNF in neurons, predicts variation in human memory, and is associated with several neurological and psychiatric disorders. Here, we show that, in magnetic resonance imaging scans of a large sample of normal individuals, this polymorphism affects the anatomy of the hippocampus and prefrontal cortex, identifying a genetic mechanism of variation in brain morphology related to learning and memory.

Figure 3.

Statistical gray matter maps of the entire brain showing volume reductions of met-BDNF carriers in comparison to val/val-BDNF have been transformed from MNI space in Talairach space and converted to z-scores. Maximal z-scores within cortical regions have been projected onto a brain surface. The figure shows that the met-BDNF group has significantly reduced cortical volume (red and yellow areas) compared with val/val-BDNF carriers being found predominantly at the lateral convexity of the frontal lobe. Peak differences (red) are also found within dorsolateral prefrontal cortical areas, which are related to memory function.

Figure 2.

Mean differences (±SEM) in hippocampal volume reduction in met-BDNF carriers relative to val/val-BDNF subjects within regions of statistical significance (p = 0.05) as shown in Figure 1. Measures for hippocampal volume have been extracted from the hippocampal cluster and transformed in percentage volume relative to val/val-BDNF while controlling for confounding variables such as age, gender, and total gray matter volume.

Figure 1.

Statistical maps of t-transformed hippocampal volume differences derived by optimized voxel-based morphometry in met relative to val/val-BDNF carriers thresholded at p = 0.05 (corrected) in coronal, sagittal, and axial views, showing bilateral significant hippocampal volume reduction in met-BDNF carriers.