An application of LARY_C : study of Cardio-vascular Rhythms Perturbations according to a Sleep Pathology (Periodic Leg Movements)

Projet SOSSOLARY_C is a software package, developped in the synchronous, data flow, parallel language SIGNAL, primary dedicated to the Autonomic Nervous System (ANS), through the analysis of physiological signals and their correlations: Heart Rate (HR), Arterial Blood Pressure (ABP), breathing, motility and electro-encephalographic activity (EEG). Our aim is to illustrate the new approach given by LARY_C for the processing of polygraphic recordings, through a clinical application, the nocturnal Periodic Leg Movements (PLM). Polygraphic recordings analysis, usually visually done, can't provide all the needed information, in particular the relations between rhythms are difficult to extract. The LARY_C library of medical signal processing provides a condense representation of the physiological rhythms; the SIGNAL synchronous environment provides the necessary tools to assess the relationships between these rhythms, in order to automatically produce a set of (cardiovascular) parameters related to an event (a PLM). We analysed the magnitude of the changes on HR and systolic ABP, the ANS behaviour through their activity in high and middle frequencies, the delays between the beginning of cardiovascular perturbations and the movement, and the relations with cortical activation reflected by an augmentation of $\alpha$ activity on the EEG. On one hundred PLM in a typical patient, cardiovascular changes related to movements are significant; the more often, they precede the movement and they are even more important in presence of high $\alpha$-activity. These preliminary results show PLM not only like a central nervous system dysfunction addressed to the motor system but rather like a dysfunction of reticular excitability responsible for motor, ANS and cortical activation. They ask the question of long term consequences of these cardiovascular swings and therefore of their specific treatement in addition to sleep and motor desorders one. Such an automatic approach seems appropriate for a better understanding of the physiopathology and to help the diagnostic in a large variety of clinical applications involving non-stationary, long duration polygraphic signals

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

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Correction: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 96 Issue: 5 Pages: 852-852 DOI: 10.1016/j.ajhg.2015.04.001 Published:MAY 7 2015Peer reviewe

Common variants in P2RY11 are associated with narcolepsy.

l e t t e r s Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genomewide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3′ untranslated region of P2RY11, the purinergic receptor subtype P2Y 11 gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10 −10 , odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The diseaseassociated allele is correlated with reduced expression of P2RY11 in CD8 + T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases

Common variants in P2RY11 are associated with narcolepsy.

Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y₁₁ gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10⁻¹⁰, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases.journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov'tresearch support, u.s. gov't, p.h.s.2011 Jan2010 12 19importedErratum in : Nat Genet. 2011 Oct;43(10):1040

Effets directs non-circadiens de la lumière médiés par la mélanopsine (un troisième mécanisme majeur de régulation du sommeil et de l'éveil)

Entre 15 et 30% de la population souffrent de troubles du sommeil, ce qui représente un enjeu majeur de santé publique et souligne la nécessité de mieux comprendre les mécanismes de régulation du sommeil. La régulation du sommeil est décrite comme un modèle à 2-processus comprenant un mécanisme circadien et homéostatique. La lumière exerce un effet sur le sommeil de deux manières distinctes: indirectement en resynchronisant l'horloge, et directement par des mécanismes qui restent mal compris. Cet effet direct est médié par des cellules spécialisées de la rétine intrinsèquement photosensibles et contenant un photopigment la mélanopsine (Opn4) mais aussi par les cônes et bâtonnets qui transfèrent l'information à ces cellules. Pour comprendre la façon dont ces effets directs influencent le sommeil et la veille, nous avons caractérisé des souris Opn4-/- et des souris sans horloge fonctionnelle (Syn10cre/creBmal1fl/-), ainsi qu un rongeur diurne, Arvicanthis ansorgei. Les objectifs de cette étude étaient les suivants: (1) identifier les voies neuronales sous-tendant les effets directs de la lumière médiés par la mélanopsine ; (2) valider ces effets chez un rongeur diurne; (3) établir une relation entre lumière, Opn4 et homéostasie du sommeil. Ce travail a permis (1) de mettre en évidence que les effets directs de la lumière représente un troisième mécanisme majeur de régulation du sommeil permettant même de maintenir un rythme veille sommeil en l absence d horloge centrale (2) de démontrer que ces effets sont inversés entre espèces diurnes et nocturnes; (3) de démontrer que la mélanopsine et la lumière sont fortement liées à la modulation de l homéostasie du sommeil.Between 15-30% of the general population is affected by sleep disorders, representing a major public health challenge, and as such a need to better understand the regulatory mechanisms of sleep and waking. This has been previously described as a 2-process model; both a circadian and homeostatic process. Light exerts an effect on sleep and wake in two distinct ways: indirectly, through the resynchronization of the clock, and directly via mechanisms that remain poorly understood. This direct effect is primarily a result of interaction with specialized cells in the retina which are intrinsically photosensitive containing the photopigment melanopsin (Opn4) in addition to rods and cones, which to a lesser extent pass information through these cells. To understand the way in which these direct effects influence sleep and waking we characterized mice lacking Opn4, and a second group possessing a functionally disabled clock (Syn10cre/creBmal1fl/-), as well as a diurnal rodent, arvicanthis ansorgei. The aims of this study were to: (1) identify the possible neural pathways to the hypothalamus transmitting the Opn4-mediated direct effects of light; (2) validate these effects in a diurnal rodent; (3) demonstrate a biological link between light, Opn4, and sleep homeostasis. This work has provided (1) strong evidence for a third regulatory mechanism of sleep and waking (direct effects of light) that is able to maintain a sleep wake rhythm in the absence of central clock (2) an inversion of this mechanism between nocturnal and diurnal species; (3) demonstration that Opn4 and light are strongly related to the modulation of homeostatic sleep process.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

Effets directs non-circadiens de la lumière médiés par la mélanopsine (un troisième mécanisme majeur de régulation du sommeil et de l'éveil)

Entre 15 et 30% de la population souffrent de troubles du sommeil, ce qui représente un enjeu majeur de santé publique et souligne la nécessité de mieux comprendre les mécanismes de régulation du sommeil. La régulation du sommeil est décrite comme un modèle à 2-processus comprenant un mécanisme circadien et homéostatique. La lumière exerce un effet sur le sommeil de deux manières distinctes: indirectement en resynchronisant l'horloge, et directement par des mécanismes qui restent mal compris. Cet effet direct est médié par des cellules spécialisées de la rétine intrinsèquement photosensibles et contenant un photopigment la mélanopsine (Opn4) mais aussi par les cônes et bâtonnets qui transfèrent l'information à ces cellules. Pour comprendre la façon dont ces effets directs influencent le sommeil et la veille, nous avons caractérisé des souris Opn4-/- et des souris sans horloge fonctionnelle (Syn10cre/creBmal1fl/-), ainsi qu un rongeur diurne, Arvicanthis ansorgei. Les objectifs de cette étude étaient les suivants: (1) identifier les voies neuronales sous-tendant les effets directs de la lumière médiés par la mélanopsine ; (2) valider ces effets chez un rongeur diurne; (3) établir une relation entre lumière, Opn4 et homéostasie du sommeil. Ce travail a permis (1) de mettre en évidence que les effets directs de la lumière représente un troisième mécanisme majeur de régulation du sommeil permettant même de maintenir un rythme veille sommeil en l absence d horloge centrale (2) de démontrer que ces effets sont inversés entre espèces diurnes et nocturnes; (3) de démontrer que la mélanopsine et la lumière sont fortement liées à la modulation de l homéostasie du sommeil.Between 15-30% of the general population is affected by sleep disorders, representing a major public health challenge, and as such a need to better understand the regulatory mechanisms of sleep and waking. This has been previously described as a 2-process model; both a circadian and homeostatic process. Light exerts an effect on sleep and wake in two distinct ways: indirectly, through the resynchronization of the clock, and directly via mechanisms that remain poorly understood. This direct effect is primarily a result of interaction with specialized cells in the retina which are intrinsically photosensitive containing the photopigment melanopsin (Opn4) in addition to rods and cones, which to a lesser extent pass information through these cells. To understand the way in which these direct effects influence sleep and waking we characterized mice lacking Opn4, and a second group possessing a functionally disabled clock (Syn10cre/creBmal1fl/-), as well as a diurnal rodent, arvicanthis ansorgei. The aims of this study were to: (1) identify the possible neural pathways to the hypothalamus transmitting the Opn4-mediated direct effects of light; (2) validate these effects in a diurnal rodent; (3) demonstrate a biological link between light, Opn4, and sleep homeostasis. This work has provided (1) strong evidence for a third regulatory mechanism of sleep and waking (direct effects of light) that is able to maintain a sleep wake rhythm in the absence of central clock (2) an inversion of this mechanism between nocturnal and diurnal species; (3) demonstration that Opn4 and light are strongly related to the modulation of homeostatic sleep process.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

Syndrome d'apnée obstructif du sommeil et oeil (étude prospective, à propos de 113 patients)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Light effects in diurnal and nocturnal species: A complex role of the spectral composition.

<p>Light is known to promote sleep in nocturnal species and alertness in day-active animals. Our hypothesis is that the opposite responses to natural polychromatic light may result from higher sensitivity of nocturnal species to green light, and diurnals to blue wavelengths, resulting in hypnogenic and alerting effects, respectively. This can be modeled as different blue and green weights on a balance, explaining either an alerting (higher sensitivity to blue) or sleep-promoting effect (greater sensitivity to green) of white light in diurnal and nocturnal species, respectively.</p