HCRT and major depressive disorder: Other work, including that by our three independent groups (Christopher V Dayas, Stephanie L. Borgland and Morgan H James), showed that orexins are potent regulators of general reward-directed behaviours, spanning food, drugs and sex, and are also integrally involved in behaviours associated with stress, anxiety and depression (Baimel et al., 2017; Mehr, Mitchison et al., 2021; Yeoh et al., 2014) (Figure 1).