Ketamine has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant MDD, one of the possible antidepressant mechanisms of ketamine may be associated with its actions on clock-gene-related molecules, leading to alterations in the circadian timekeeping of the central clock, and/or with its efects on entrainment circuits that synchronise the central clock with external lighting cycles. Here, CLOCK is linked to major depressive disorder.