Chronobiological theories of mood disorder.

Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: "chronobiology," "mood," "sleep," and "circadian rhythms." We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.

Light Hygiene: Time to make preventive use of insights--old and new--into the nexus of the drug light, melatonin, clocks, chronodisruption and public health.

Light is, clearly, a key to life on Earth and light, equally clearly, determines biological rhythmicity in organisms. Light does the latter by setting internal or endogenous clocks which allow a multitude of species, including man, to adjust their lives to changing external or environmental conditions. Critical changes over time occur from day to night and throughout the year. In this paper, we sum up how visible light provides electromagnetic information about environmental "time" via the ocular interface of newly discovered photoreceptive cells to a master clock in our brain, viz the suprachiasmatic nuclei [SCN], and how the SCN translate this input, with melatonin as a key biologic intermediary, into endogenous or biological time. We summarize experimental and epidemiological evidence suggesting how chronodisruption, a relevant disturbance of the temporal organization or order of physiology, endocrinology, metabolism and behaviour, is probably detrimental for human beings. On the basis of our synthesis, and in line with suggestions by other researchers voiced decades ago, light must, functionally, be considered as a drug equivalent. In this vein, the very timing, quality (wavelength), quantity (dose) and side effects, including chronodisruption, of light exposures can be critically important for health and disease in man. As a promising means to foster public health, we advocate an appropriate balance of exposures to the key Zeitgeber light in terms of "light hygiene", implying strong and appropriate rather than weak and confusing temporal information. This focus on "light hygiene", and thus on the key Zeitgeber light, does not mean to ignore that there are multiple entrainment pathways for our circadian clocks. Indeed, when dealing with light, chronodisruption and a multitude of adverse health effects, we ultimately need to consider Zeitgeber cues, and their possible interplay, beyond light alone. Confusions of the temporal programmes in humans can also stem from physical and social activities, stress and facets of food intake. And yet, since light possesses a rather unique and exclusive Zeitgeber role and in view of its ubiquitous nature, a specific, preventative focus on "light hygiene", as a contribution to a general "Zeitgeber hygiene", is warranted.

The chronobiology of the Natal mole-rat, Cryptomys hottentotus natalensis.

The Natal mole-rat, Cryptomys hottentotus natalensis, rarely, if ever, is exposed to external light cues because it occurs in completely sealed tunnel systems. As a result, their classical visual system is regressed, and therefore, their circadian system is expected proportionally to be expanded. Locomotor activity was investigated under a number of different photic regimes. Nine of the 12 mole-rats exhibited endogenous circadian rhythms of locomotor activity under constant darkness, with a mean free run period of 24.13 h (range 23.93-24.13 h), with these animals entrained to a light-dark cycle (12 L:12 D). Because C. hottentotus natalensis are able to entrain their locomotor activity to an external light source, light must reach the suprachiasmatic nucleus (SCN), suggesting a functional circadian clock. A clear day-night rhythm of melatonin secretion in animals housed under a neutral photoperiod (12 L:12 D) was observed, with higher melatonin concentrations in the dark compared with the light phase. The rhythm was maintained after the animals were transferred to either continuous light (LL) or dark (DD), suggesting that the endogenous rhythm was maintained under acute exposure to light and dark. However, under DD, the rhythm appeared to shift slightly, potentially as a result of the rhythm free running. These results show that C. hottentotus natalensis has endogenous rhythms of both locomotor activity and melatonin secretion, which are modulated by light.

Light variability in the modern neonatal nursery: chronobiologic issues.

The role that nursery light variability may play in modulating infant biological rhythms is being studied in Stanford Medical Center's Neonatal Intensive Care (NICU) and Intermediate Care (IN) Nurseries. In this investigation, spatial and temporal variability in illuminance was determined at 20 sites within each nursery over a 5-day period. The analysis of 240 measurements at 30 min intervals from each site revealed marked variability in illumination with respect to both time and position in the nursery. These aperiodic lighting patterns differed greatly from the published characterization of NICUs as having 'constant' illumination. Light pulses of variable frequency, intensity, and duration were common at each of the 40 bedsites studied. Given the powerful impact of light on circadian rhythmicity and sleep in adults, the results from this study suggest that modern NICU lighting, while implemented to facilitate intensive care, may have adverse effects on infant development. Future studies on the influence of light on biological rhythmicity and sleep are essential to provide a framework for clinical and environmental interventions, which may play a significant role in improving developmental outcome in hospitalized preterm or term infants.