Dysfunctional Circadian Rhythms and Mood Disorders: Opportunities for Novel Therapeutic Approaches

Abstract

Discoveries in the molecular genetics of the circadian clock and the introduction of the antidepressant agent, agomelatine, with effects on circadian rhythms, have revived interest in rhythm disturbances as an aetiologically significant factor in the pathogenesis of mood disorders. There is also stimulated interest in new therapeutic modalities. Abnormal patterns of circadian timekeeping characterise a variety of psychiatric disorders, particularly major depressive disorder and bipolar disorder. The prevalence of circadian dysfunction in psychiatric disorders suggests that the human circadian system holds important clues regarding the aetiology of illnesses. Evidence for disturbances in circadian rhythms comprises the cyclic nature of the disorders themselves and their symptoms. Furthermore, studies of rhythmic physiological processes and of hormone secretion have provided additional evidence of the desynchrony of biological rhythms. Identification of the physiological basis for specific circadian dysfunctions may be helpful for designing selective drug treatments that target and normalise timekeeping disorders. While it remains debatable whether disturbances of circadian rhythms are causal or the consequence of mood disorders, there is, nonetheless, a compelling rationale that restoration of the circadian system may have potential beneficial therapeutic outcomes. The present review examines the evidence for circadian rhythm disturbances in major depression and bipolar disorder. It further examines the extent to which an interaction with the molecular clock can be utilised as an approach to the therapeutics of these disorders.