Circadian abnormalities, molecular clock genes and chronobiological treatments in depression

A long-standing challenge in the treatment of depression is the development of a rapidly acting antidepressant. Conventional antidepressants typically require 2-8 weeks for clinical remission. In contrast, chronobiological interventions such as sleep deprivation treatment dramatically reduce depressive symptoms within 24-48 h in 40-60% of depressed subjects. It is hypothesized that fast-acting treatments for depression may alter circadian rhythms through chronobiological mechanisms relevant to clock gene function.

A bibliographic review using Entrez PubMed with Boolean search terms 'circadian' and 'depressive' identified more than 1000 clinical papers published over a 40-year period (1966-present).

A large body of clinical data reports that sleep, temperature, hormone and mood changes in depression are consistent with disturbances in circadian-related processes.

Consensus has not been achieved in terms of defining underlying chronobiological mechanisms for optimal methods to produce rapid and sustained antidepressant responses to circadian interventions.

Chronobiological augmentation using combinations of sleep deprivation with light therapy and/or sleep phase advance in medicated patients supports a clinical strategy for accelerating and sustaining antidepressant responses.

Advances in technology including improved assays for clock gene expression will facilitate exploring the role of clock genes and may lead to new rapidly acting antidepressant strategies and potential novel drug targets.