BackgroundDaily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work.MethodsNewly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses.ResultsNight-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work).ConclusionsSleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental “stress” to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy.

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK and hPER3 proteins, respectively. In addition, hCLOCK expression is affected by glucocorticoids, consistent with the sex-dependency of the genetic associations and the modulation of glucocorticoid-mediated stress response, providing a mechanism by which the circadian clock controls outputs that may affect psychiatric disorders. We conclude that genetic polymorphisms in circadian genes (especially hClock and hPer3, where functional assays could be tested) influence risk of developing depression in a sex- and stress-dependent manner. These studies support a genetic connection between circadian disruption and mood disorders, and confirm a key connection between circadian gene variation and major depression.

Light can impact psychobiological processes in a healthy or harmful way, challenging designers to better understand the resources they are manipulating. The present exploratory study compared two forms of office lighting which differed in correlated colour temperatures and light level. A holistic approach, comprising visual, emotional and biological dimensions, was used to assess the lighting conditions that could favour productivity and well-being by means of the identification of congruent relationships between objective and subjective measurements in response to light stimuli. The former included analyses of melatonin and cortisol, and the latter were psychological instruments for measuring transitory mood, somnolence, and visual comfort. Controlled experiments were run in a laboratory with a repeated measures design, which yielded fifty-six evaluations. Although no extreme ranges of correlated colour temperatures were used in this study, the spectral blue component present in the correlated colour temperature of approximately 4000 K, and also provided by the light-emitting diodes system at a higher light level, could have contributed to render most of the strong effects on the inter and intra correlations among the psychobiological responses. The mediator role of the psychological profile of the individuals was demonstrated by the significant predictive value of the perceived stress measures.

Light can impact psychobiological processes in a healthy or harmful way, challenging designers to better understand the resources they are manipulating. The present exploratory study compared two forms of office lighting which differed in correlated colour temperatures and light level. A holistic approach, comprising visual, emotional and biological dimensions, was used to assess the lighting conditions that could favour productivity and well-being by means of the identification of congruent relationships between objective and subjective measurements in response to light stimuli. The former included analyses of melatonin and cortisol, and the latter were psychological instruments for measuring transitory mood, somnolence, and visual comfort. Controlled experiments were run in a laboratory with a repeated measures design, which yielded fifty-six evaluations. Although no extreme ranges of correlated colour temperatures were used in this study, the spectral blue component present in the correlated colour temperature of approximately 4000 K, and also provided by the light-emitting diodes system at a higher light level, could have contributed to render most of the strong effects on the inter and intra correlations among the psychobiological responses. The mediator role of the psychological profile of the individuals was demonstrated by the significant predictive value of the perceived stress measures. References Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E, Rollag MD. Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor. Journal of Neuroscience 2001; 21: 6405–6412. Lucas RJ, Peirson SN, Berson DM, Brown TM, Cooper HM, Czeisler CA, Figueiro MG, Gamlin PD, Lockley SW, O’Hagan HB, Price LLA, Provencio I, Skene DJ, Brainard GC. Measuring and using light in the melanopsin age. Trends in Neurosciences 2014; 37: 1–9. Rea MS, Figueiro MG. A working threshold for acute nocturnal melatonin suppression from ‘white’ light sources used in architectural applications. Journal of Carcinogenesis and Mutagenesis 2013. DOI: 10.4172/2157-2518- 1000150. Rea MS, Figueiro MG. Light as a circadian stimulus for architectural lighting. Lighting Research and Technology First published 6 December 2016. DOI: 1477153516682368. Rea MS. The lumen seen in a new light: Making distinctions between light, lighting and neuroscience. Lighting Research and Technology 2015; 47: 259–280

A high-throughput cell-based screen identified redox-active small molecules that produce a period lengthening of the circadian rhythm. The strongest period lengthening phenotype was induced by a phenazine carboxamide (VU661). Comparison to two isomeric benzquinoline carboxamides (VU673 and VU164) shows the activity is associated with the redox modulating phenazine functionality. Furthermore, ex vivo cell analysis using optical redox ratio measurements shows the period lengthening phenotype to be associated with a shift to the NAD/FAD oxidation state of nicotinamide and flavine coenzymes.