NR3C1 and major depressive disorder: Indeed, altered hypothalamic pituitary axis activity may be restricted mainly to the subset of MDD cases associated with trauma.74 However, our failure to see positive signals for NFκB and GR activation, when other transcription control pathways such as CREB/ATF and NRF2 show detectable differences in activity, suggests that NF-κB and GR do not constitute the most sensitive or clinically useful TF pathway biomarkers of MDD.