From earliest times, psychiatrists have described biological rhythm disturbances as characteristic of mood disorders. The present flourishing of circadian biology has revealed the molecular basis of 24-h rhythmicity driven by 'clock' genes, as well as the importance of zeitgebers (synchronisers). Winter depression was first modelled on regulation of animal behaviour by seasonal changes in daylength, and led to application of light as the first successful chronobiological treatment in psychiatry. Light therapy has great promise for many other disorders (e.g. sleep-wake cycle disturbances in Alzheimer's dementia, bulimia, premenstrual disorder, depression during pregnancy) and, importantly, as an adjuvant to antidepressant medication in major non-seasonal depression. The pineal hormone melatonin is also a zeitgeber for the human circadian system, in addition to possessing direct sleep-promoting effects. Chronobiology has provided efficacious non-pharmaceutical treatments for mood disorders (such as sleep deprivation or light therapy) as well as novel approaches to new drugs (e.g. agomelatine).

The Committee on Chronotherapeutics was recently formed by the International Society for Affective Disorders (ISAD), which has asked us to provide a consensus review of chronotherapeutics (light and wake therapy) in affective disorders. We consider these non-pharmaceutical, biologically based therapies to be potentially powerful adjuvants ready for clinical application. We also stress the need for additional studies, both in-patient and out-patient, to broaden the evidence base for indications and efficacy.

Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. The ipRGCs project to the circadian clock in the suprachiasmatic nuclei and thereby ensure entrainment to the 24-hour day-night cycle, and changes in daylength trigger the appropriate seasonal behaviours. The ipRGCs also project to the perihabenular nucleus and surrounding brain regions that modulate mood, stress and learning in animals and humans. Given that light has strong direct effects on mood, cognition, alertness, performance, and sleep, light can be considered a "drug" to treat many clinical conditions. Light therapy is already well established for winter and other depressions and circadian sleep disorders. Beyond visual and non-visual effects via the retina, daylight contributes to prevent myopia in the young by its impact on eye development, and is important for Vitamin D synthesis and bone health via the skin. The sun is the most powerful light source and, dependent on dose, its ultraviolet radiance is toxic for living organisms and can be used as a disinfectant. Most research involves laboratory-based electric light, without the dynamic and spectral changes that daylight undergoes moment by moment. There is a gap between the importance of daylight for human beings and the amount of research being done on this subject. Daylight is taken for granted as an environmental factor, to be enjoyed or avoided, according to conditions. More daylight awareness in architecture and urban design beyond aesthetic values and visual comfort may lead to higher quality work and living environments. Although we do not yet have a factual basis for the assumption that natural daylight is overall "better" than electric light, the environmental debate mandates serious consideration of sunlight not just for solar power but also as biologically necessary for sustainable and healthy living.

Affective disorder during pregnancy is a common condition requiring careful judgment to treat the depression while minimizing risk to the fetus. Following up on promising pilot trials, we studied the efficacy of light therapy. Twenty-seven pregnant women with nonseasonal major depressive disorder according to DSM-IV (outpatients, university polyclinic) were randomly assigned to 7,000 lux fluorescent bright white or 70 lux dim red (placebo) light administered at home in the morning upon awakening for 1 h/d in a 5-week double-blind trial carried out between October 2004 and October 2008. Clinical state was monitored weekly with the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS) with Atypical Depression Supplement (SIGH-ADS). Changes of rating scale scores over time were analyzed with the general linear model. Differences from baseline of SIGH-ADS and 17-item HDRS scores at every time point were the dependent variables, time was the within-subjects factor, and treatment was the between-subjects factor. The model also included baseline score of depression and gestational age at intervention start. The superiority of bright light over dim light placebo was shown for both SIGH-ADS (R² = 0.251; F(3,23) = 3.91; P < .05) and HDRS (R² = 0.338; F(3,23) = 5.42; P < .01) when analyzing the week-by-week change from baseline, and HDRS scores showed a significant interaction of treatment with time (F(4,92) = 2.91; P < .05). Categorical analysis revealed that the response rate (HDRS ≥ 50% improvement) at week 5 was significantly greater for bright light (81.3%, n = 16) than for placebo light (45.5%, n = 11) (P < .05). Remission (final score ≤ 8) was attained by 68.6% versus 36.4%, respectively (P < .05). Expectation ratings did not differ significantly between groups. Bright white light treatment for 5 weeks improved depression during pregnancy significantly more than placebo dim red light. The study provides evidence that light therapy, a simple, cost-effective antidepressant modality with minimal side effects for the mother and no known risk for the unborn child, may be a useful nonpharmacologic approach in this difficult situation. clinicaltrials.gov Identifier: NCT01043289.

Diurnal variation of depressive symptoms appears to be part of the core of depression. Yet, longitudinal investigation of an individual's pattern, regularity, relation to clinical state, and clinical improvement reveals little homogeneity. Morning lows, afternoon slump, evening worsening-all can occ …