Circadian disruptions and brain clock dysregulation in mood disorders

The circadian system, composed of a network of brain and peripheral 24-hour clocks and oscillators, allows organisms to anticipate and synchronize to natural daily events. The day–night cycle is the dominant timing signal to align circadian clocks to the external time. Thereby, exposure to aberrant light–dark cycles leads to disruptions of the circadian system, evoking different health issues, including mental or affective ones. Humans with circadian misalignments, such as those observed in jet-lag-exposed people or shift workers, and animal models of clock disturbances show mood alterations such as anxiety and depressive-like behaviors. The mechanisms underlying the physiopathology of mood disorders in circadian disruption may imply an altered functioning of the main clock in the suprachiasmatic nucleus, from other central oscillators, or a loss of internal synchrony between them. This Review outlines the current knowledge on the link between circadian perturbations and mood disorders in humans and animal models, and the possible neurobiological mechanisms involved. This Review explores the link between mood disorders and circadian disruptions, including social jet lag and shift work, and offers new perspectives for therapeutic development in future chronobiology research.