I suggest that overstimulation of LHb causes discomfort and aversion by down-regulating serotonin signaling (Wang and Aghajanian, 1977), lack of which disinhibits AI, dACC, globus pallidus interna (GPi), LHb (presynaptic LHb inhibition found by Shabel et al., 2012) and pain pathway output, thus potentiates learned helplessness, depression and anxiety. This evidence concerns the gene LHB and major depressive disorder.