Alerting or Somnogenic Light: Pick Your Color.

In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues describes an even more complex role for the acute effects of light. In mice, blue light acutely causes behavioral arousal, whereas green wavelengths promote sleep. These opposing effects are mediated by melanopsin-based phototransduction through different neural pathways. These findings reconcile nocturnal and diurnal species through a common alerting response to blue light. One can hypothesize that the opposite responses to natural polychromatic light in night- or day-active animals may reflect higher sensitivity of nocturnal species to green, and diurnals to blue wavelengths, resulting in hypnogenic and alerting effects, respectively. Additional questions remain to be clarified. How do different light wavelengths affect other behaviors such as mood and cognition? How do those results apply to humans? How does light pose either a risk or benefit, depending on whether one needs to be asleep or alert? Indeed, in addition to timing, luminance levels, and light exposure duration, these findings stress the need to understand how best to adapt the color spectrum of light to our needs and to take this into account for the design of daily lighting concepts-a key challenge for today's society, especially with the emergence of LED light technology

Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10 <sup>cre/cre</sup> Bmal1 <sup>fl/-</sup> ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4 <sup>-/-</sup> ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders. Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method. Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders. Conclusion: The administration of prolonged release melatonin at 2–10 mg, 1–2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders

Melanopsin as a Sleep Modulator: Circadian Gating of the Direct Effects of Light on Sleep and Altered Sleep Homeostasis in Opn4−/− Mice

Analyses in mice deficient for the blue-light-sensitive photopigment melanopsin show that direct effects of light on behavior and EEG depend on the time of day. The data further suggest an unexpected role for melanopsin in sleep homeostasis

Dialysis delivery of an adenosine A 2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A 2A receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A 2A receptor agonist 2- p- (2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 μm CGS and significantly decreased by dialysis with 10 and 100 μm CGS. Co-administration of the adenosine A 2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nm) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 μm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (−51% in h 1; −54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A 2A receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A 2A receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66018/1/j.1471-4159.2006.03700.x.pd

Mass correlation between light and heavy reaction products in multinucleon transfer 197Au+130Te collisions

We studied multinucleon transfer reactions in the 197Au+130Te system at Elab=1.07 GeV by employing the PRISMA magnetic spectrometer coupled to a coincident detector. For each light fragment we constructed, in coincidence, the distribution in mass of the heavy partner of the reaction. With a Monte Carlo method, starting from the binary character of the reaction, we simulated the de-excitation process of the produced heavy fragments to be able to understand their final mass distribution. The total cross sections for pure neutron transfer channels have also been extracted and compared with calculations performed with the grazing code

Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset

Experimental investigations of the sub-Coulomb 12C+12C and 12C+16O reactions

Cluster resonances in light heavy-ion systems like 12C+12C and 12C+16O may have a major impact on astrophysics stellar scenarios. Resonant radiative capture reactions have been studied for these systems at energies at and slightly below their Coulomb barriers to investigate the possible 12C-12C and 12C-16O molecular origin of the resonances. Spins have been attributed to the resonances and specificities of their γ-decay have been identified. At deep sub-barrier energies, a fusion cross section measurement using the particle-γ coincidence technique is discussed for the 12C+12C system. A new project is presented to possibly extend the 12C+12C S low-energy S factor study