Coordonnateur: Patrice Bourgin
Co-coordonnateur: Gilles Bertschy
General scopes and previous achievements:
In the last few years major progress in animal models towards the understanding of basic sleep regulatory mechanisms has been made by our group, in particular the dissection and quantification of phototransduction and neuronal pathways by which light influences sleep, alertness and mood. Our findings establish a new model of sleep regulation based on three main processes instead of the “classical two process model based on homeostatic and circadian processes”. Similarly, in humans we have made significant progress towards the interrelation between sleep pressure, circadian phase and mood and wellbeing. We have conceptualized the inter-relation between excessive daytime somnolence and depression. We have characterized sleep regulatory mechanisms disturbances in specific sleep disorders and we have participated in key genome wide association studies (GWAS) that clarified the pathogenesis of narcolepsy as an autoimmune process. Finally, we have evaluated novel indications of light therapy.
Future projects in NEUROGENYCS:
Our goal is to validate in humans the proposed process model of sleep regulation and to demonstrate how it predicts the 24h temporal organization of sleep and waking in relation to the external cues, a goal that will be possible thanks to CIRCSom. The clinical research approach is designed to understand the pathogenesis of disorders of sleep regulation, including circadian rhythm sleep disorders (CRSD) and RLS. The approach also applies to patients with complaints of hypersomnia or insomnia, which corresponds to a broad spectrum of disturbances from well-defined entities to sleep/circadian disturbances associated with mood impairment. Therefore, the goal is to define homogeneous subgroups of well-characterized patients based on new clinical endpoints. This includes the identification of biomarkers, with a special focus on markers of sleep regulatory dysfunction (as for ex. EEG delta activity for sleep homeostasis, fibroblast period or melatonin profile for the circadian drive …) as well as genetic markers. The genetic analysis will be applied in particular to CRSD based on a national and international recruitment of subjects with an extreme phenotype (extreme phase delay or chronotype, TMT2). Overall, this will allow us to establish and validate clinical design approaches combining chronotherapeutics and pharmacological compounds in order to define personalized strategies adapted to the “right patient”, that will be used to further investigate new treatments.