Chronotherapeutics and psychiatry: setting the clock to relieve the symptoms

Circadian rhythms are near 24-h cycles in a number of physiological and behavioural parameters and the underpinning circadian timing systems is one of the key homeostatic regulatory systems in mammalian physiology. Many common psychiatric conditions are associated with disrupted sleep, including a common occurrence of delayed or advanced phase sleep syndromes, which in themselves may be indicative of dysregulated circadian timing in these disorders. In this article we discuss the evidence for abnormal circadian rhythms in seasonal affective disorder, bipolar disorder and attention deficit/hyperactivity disorder. Much of this evidence suggest that these conditions are associated with either phase delays or phase advances of core phase markers of the circadian clock such as melatonin or core body temperature, suggesting the presence of circadian desynchrony in these conditions. We also highlight findings that pharmacological and/or behavioural interventions that ameliorate circadian misalignments are efficacious in producing symptomatic relief, suggesting an intrinsic link between the circadian and affective systems that can be manipulated for clinical benefit.