We have previously observed this model in the regulation of BDNF promoter 4 whereby a highly conserved region of the BDNF locus, containing a SNP associated with depression (BE5.2), caused significant repression of BDNF promoter 4 within 3 different primary cell types (hippocampus, cortex and amygdala).22 These analyses of the BDNF locus suggested an important role for selective negative regulation in the modulation of inducible gene expression in the brain. Here, BDNF is linked to major depressive disorder.