Vol 5 n° 4 - Chronobiology and Mood Disorders
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n order for Dialogues in Clinical Neuroscience to be truly designated “dialogues,” I will raise specific and critical questions about the putative circadian rhythm dis- turbances in depression, provide a model within which to understand them, and summarize the present status and application  of  chronobiological  therapies.  This  short overview will not go into detail of the clinical and exper- imental findings related to biological rhythms in depres- sion, which have been extensively reviewed elsewhere.1-9 Chronobiologists predicate their work on a primary axiom, that temporal order is essential for health. Psychological, behavioral, physiological, and  hormonal  rhythms  are specifically and functionally timed (entrained or syn- chronized) with respect to sleep and the day-night cycle. The converse premise implies that temporal disorder must have clinical correlates. Rhythmic characteristics of S t a t e   o f   t h e   a r t 3 1 5 Chronobiology and mood disorders Anna Wirz-Justice, PhD I Keywords: major depression; seasonal affective disorder; circadian rhythm; sleep deprivation; light therapy; melatonin Author  affiliations:  Centre  for  Chronobiology,  Psychiatric  University  Clinic, Basel, Switzerland Address   for   correspondence:   Prof   Dr   Anna   Wirz-Justice, Centre for Chronobiology, Psychiatric University Clinic, Wilhelm Klein Strasse 27, CH-4025 Basel, Switzerland
(e-mail: anna.wirz-justice@pukbasel.ch) The clinical observations of diurnal variation of mood and early morning awakening in depression have been incorpo- rated into established diagnostic systems, as has the seasonal modifier defining winter depression (seasonal affective dis- order, SAD). Many circadian rhythms measured in depressive patients are abnormal: earlier in timing, diminished in ampli- tude, or of greater variability. Whether these disturbances are of etiological significance for the role of circadian rhythms in mood disorders, or a consequence of altered behavior can only be dissected out with stringent protocols (eg, constant routine or forced desynchrony). These protocols quantify contributions of the circadian pacemaker and a homeostatic sleep process impacting on mood, energy, appetite, and sleep. Future studies will elucidate any allelic mutations in “circadian clock”–related or “sleep”-related genes in depression. With respect to treatment, antidepressants and mood stabilizers have no consistent effect on circadian rhythmicity. The most rapid antidepressant modality known so far is nonpharmacological: total or partial sleep deprivation in the second half of the night. The disadvantage of sleep depri- vation, that most patients relapse after recovery sleep, can be prevented by coadministration of lithium, pindolol, sero- tonin (5-HT) reuptake inhibitors, bright light, or a subsequent phase-advance procedure. Phase advance of the sleep- wake cycle alone also has rapid effects on depressed mood, which lasts longer than sleep deprivation. Light is the treatment of choice for SAD and may prove to be useful for nonseasonal depression, alone or as an adjunct to medica- tion. Chronobiological concepts emphasize the important role of zeitgebers to stabilize phase, light being the most impor- tant, but dark (and rest) periods, regularity of social schedules and meal times, and use of melatonin or its analogues should also be considered. Advances in chronobiology continue to contribute novel treatments for affective disorders. © 2003, LLS SAS Dialogues Clin Neurosci. 2003;5:315-325. Copyright © 2003 LLS SAS.  All rights reserved www.dialogues-cns.org