British Medical Bulletin Advance Access originally published online on May 17, 2008
British Medical Bulletin 2008 86(1):23-32; doi:10.1093/bmb/ldn019
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Circadian abnormalities, molecular clock genes and chronobiological treatments in depression
1 University of Southern California, Los Angeles, CA, USA
2 Department of Psychiatry, University of California, Irvine, Irvine CA, USA
* Correspondence to: Steven G. Potkin, Professor of Psychiatry, Robert R. Sprague Chair in Brain Imaging, and Director, Clinical Psychiatric Research Department: Psychiatry and Human Behavior, University of California Irvine, School of Medicine, Bldg 3, Rt 88, Rm 310-BIC, Irvine Hall, CA 92697, USA. E-mail: sgpotkin{at}uci.edu
Background: 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.
Sources of data: 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).
Areas of agreement: A large body of clinical data reports that sleep, temperature, hormone and mood changes in depression are consistent with disturbances in circadian-related processes.
Areas of controversy: 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.
Growing points: 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.
Areas timely for developing research: 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.
Keywords: circadian rhythm • depression • sleep deprivation
Accepted for publication April 29, 2008.