MET BDNF protects against morphological S allele effects of 5-HTTLPR

Top row: Both the MET allele of val66met BDNF (left) and the S allele of 5-HTTLPR affect regional brain volume, measured by voxel-based morphometry and magnetic resonance imaging. Middle row: These two risk variants interact epistatically: whereas carriers of the MET BDNF allele exhibit a diminished and almost absent effect of the 5-HTTLPR S allele (left), carriers of BDNF VAL/VAL genotype (right) show a significant impact of the S allele on rACC morphometry, indicating biological epistasis of BDNF and 5-HTTLPR. Lower row: Functional implications. Presence of the MET allele protects against the emergence of a dysfunctional amygdala–cingulate circuit for the extinction of amydala reactivity linked to the S allele of 5-HTTLPR, reducing the vulnerability for environmental adversity that is thought to underlie the association of 5-HTTLPR with clinical depression. For more information on this topic see the paper by Pezawas et al. on pages 709–716.