Gene variants for the orexin peptides and, especially, their G protein-coupled receptors, OX1 and OX2, have been identified (Figures 1, 2), and investigated in many CNS disorders, including sleep and wakefulness (Lin et al., 1999), polydipsia in schizophrenia (Meerabux et al., 2005; Fukunaka et al., 2007), panic disorder (Annerbrink et al., 2011), mood disorders (Rainero et al., 2011a), migraine (Schürks et al., 2007b; Rainero et al., 2011b), and cluster headache (Rainero et al., 2004). Here, HCRT is linked to mood disorder.