Consistent with challenge studies using a cholinesterase inhibitor to increase nAChR occupancy (Esterlis et al., 2013), imaging studies suggest that brain ACh levels may be higher in individuals with major depressive or bipolar disorder when they are actively depressed (Saricicek et al., 2012; Hannestad et al., 2013). The gene discussed is CHRNA4; the disease is major depressive disorder.