Sleep-wake regulation; Synaptic plasticity; Homeostasis; Brain imaging (PET, 1H-MRS, fMRI); Human genetics; mGluR5; Brain-derived neurotrophic factor (BDNF); Adenosine; Idiopathic hypersomnia; Major depressive disorder; Single nucleotide polymorphism; Vigilance; Mood
Urry Emily, Jetter Alexander, Holst Sebastian C., Berger Wolfgang, Spinas Giatgen A., Langhans Wolfgang, Landolt Hans-Peter (2017), A case-control field study on the relationships among type 2 diabetes, sleepiness, and habitual caffeine intake, in
J Psychopharm, 233.
Urry Emily, Jetter Alexander, Landolt Hans-Peter (2016), Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual caffeine intake, in
Nutr Metab, e66.
(2015), Caffeine, the circadian clock, and sleep, in
Science, 349(6254), 1289-1289.
(2015), Catechol-O-methyltransferase, dopamine, and sleep-wake regulation, in
Sleep Medicine Reviews, 22, 47-53.
Holst Sebastian C., Landolt Hans Peter (2015), Sleep homeostasis, metabolism, and adenosine, in
Current Sleep Medicine Reports, 27.
Landolt Hans Peter, Sousek Alexandra, Holst Sebastian C. (2014), Acute and chronic effects of sleep deprivation, in Bassetti Claudio (ed.), Wiley, Regensburg, 49.
(2014), Adenosine, caffeine, and performance: from cognitive neuroscience of sleep to sleep pharmacogenetics, in
Current Topics in Behavioral Neurosciences, 25, 331-366.
(2014), Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans, in
Journal of Neuroscience, 34(2), 566-573.
(2014), Light modulation of human sleep depends on a polymorphism in the clock gene Period3, in
Behavioural Brain Research, 271, 23-29.
(2014), Sleep ability mediates individual differences in the vulnerability to sleep loss: Evidence from a PER3 polymorphism, in
Cortex, 52(1), 47-59.
(2014), The circadian regulation of sleep: Impact of a functional ADA-polymorphism and its association to working memory improvements, in
PLoS ONE, 9(12), e113734.
(2014), Time-on-task decrement in vigilance is modulated by inter-individual vulnerability to homeostatic sleep pressure manipulation, in
Frontiers in Behavioral Neuroscience, 8(MAR), 59.
(2013), Effect of prolonged wakefulness on electroencephalographic oscillatory activity during sleep, in
Journal of Sleep Research, 23(3), 253-260.
Landolt Hans Peter, Urry Emily (2013), Functional neuroimaging: Sedating medication effects, in Nofzinger Eric (ed.), Cambridge University Press, Cambridge, 396.
Landolt Hans Peter (2013), Genetic effects, in Kushida Clete (ed.), Academic Press, Philadelphia, 251.
(2013), Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep-wake cycles in young adults, in
Chronobiology International, 31(5), 705-714.
Hefti Katharina, Holst Sebastian C., Sovago Judit, Bachmann Valerie, Buck Alfred, Ametamey Simon M., Scheidegger Milan, Berthold Thomas, Gomez-Mancilla Baltazar, Seifritz Erich, Landolt Hans-Peter (2013), Increased Metabotropic Glutamate Receptor Subtype 5 Availability in Human Brain After One Night Without Sleep, in
BIOLOGICAL PSYCHIATRY, 73(2), 161-168.
(2013), Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism, in
Journal of Biological Rhythms, 29(2), 119-130.
(2013), Psychomotor Vigilance Task demonstrates impaired vigilance in disorders with excessive daytime sleepiness, in
Journal of Clinical Sleep Medicine, 10(9), 1019-1024.
Bosch Oliver G., Rihm Julia S., Scheidegger Milan, Landolt Hans-Peter, Staempfli Philipp, Brakowski Janis, Esposito Fabrizio, Rasch Bjoern, Seifritz Erich (2013), Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans, in
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(48), 19597-19602.
(2013), Sleep habits, sleep quality and sleep medicine use of the swiss population results from a new survey in a representative sample, in
Therapeutische Umschau, 71(11), 637-646.
Bachmann Valérie, Klaus Federica, Bodenmann Sereina, Schäfer Nikolaus, Brugger Peter, Huber Susanne, Berger Wolfgang, Landolt Hans-Peter (2012), Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans., in
Cerebral cortex (New York, N.Y. : 1991), 22(4), 962-70.
Landolt Hans-Peter (2012), Génétique du Sommeil Normal et des Rythmes Circadiens, in Billiard Michel (ed.), Masson, Paris, 45-57.
Chellappa SL, Viola AU, Schmidt C, Bachmann V, Gabel V, Maire M, Reichert CF, Valomon A, Gotz T, Landolt HP, Cajochen C (2012), Human Melatonin and Alerting Response to Blue-Enriched Light Depend on a Polymorphism in the Clock Gene PER3, in
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 97(3), 433-437.
Bodenmann S, Hohoff C, Freitag C, Deckert J, Rétey J V, Bachmann V, Landolt H-P (2012), Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation., in
British journal of pharmacology, 165(6), 1904-13.
Landolt Hans-Peter, Rétey Julia V, Adam Martin (2012), Reduced neurobehavioral impairment from sleep deprivation in older adults: contribution of adenosinergic mechanisms., in
Frontiers in neurology, 3, 62-62.
Bachmann Valérie, Klein Carina, Bodenmann Sereina, Schäfer Nikolaus, Berger Wolfgang, Brugger Peter, Landolt Hans-Peter (2012), The BDNF Val66Met polymorphism modulates sleep intensity: EEG frequency- and state-specificity., in
Sleep, 35(3), 335-44.
Landolt Hans-Peter (2011), Genetic determination of sleep EEG profiles in healthy humans., in
Progress in brain research, 193, 51-61.
(2011), Sleep homeostasis, adenosine, caffeine, and narcolepsy, in Baumann Christian (ed.), Springer, New York, 85-92.
Holst Sebastian C., Müller Thomas, Valomon Amandine, Seebauer Britta, Berger Wolfgang, Landolt Hans-Peter, Functional polymorphisms in dopaminergic genes modulate neurobehavioral and neurophysio-logical consequences of sleep deprivation, in
Sci Rep.
Landolt Hans Peter, Djik Derk-Jan, Genetics of sleep in healthy humans, in Kryger Meir (ed.), Elsevier, Philadelphia.
Holst Sebastian C., Valomon Amandine, Landolt Hans Peter, Sleep pharmacogenetics: personalized sleep-wake therapy, in
Annual Reviews in Pharmacology and Toxicology.
1. Background: The unknown function(s) of sleep constitute one of the remaining frontiers in today’s biomedical research. The homeostatic facet of sleep-wake regulation is the most important aspect of sleep in relation to its function. According to this principle, elevated sleep need following sleep deprivation is counteracted by prolonged sleep duration and, especially, by enhanced sleep intensity. A highly predictable and reliable marker of sleep intensity is electroencephalographic (EEG) slow-wave activity (SWA) in non-rapid-eye-movement sleep. Accumulating evidence indicates that the changes in SWA are causally linked to local synaptic processes reflecting the duration and quality of prior wakefulness. Recent research of us and others strongly suggests that Homer 1a, brain-derived neurotrophic factor, adenosine deaminase, adenosine A2A receptor, and other molecular markers of synaptic plasticity, play an important role in sleep homeostasis. All these molecules interact either directly or indirectly with the metabotropic glutamate receptor subtype 5 (mGluR5). Thus, we will investigate whether (1) glutamatergic mechanisms in general, and mGluR5 in particular, are critically involved in sleep homeostasis, and (2) whether abnormalities in these mechanisms are associated with reduced vigilance and depressed mood in patients with idiopathic hypersomnia (iHS) and major depressive disorder (MDD).2. Specific Aims: (1) To elucidate the roles for mGluR5 and glutamine / glutamate in sleep-wake regulation and disease-related disturbances of vigilance and mood. (2) To provide the rationale for a potential novel strategy to pharmacologically treat disturbed sleep, vigilance and mood in neurological and psychiatric disorders. (3) To gain further insights into the genetic influences on sleep-wake homeostasis in humans.3. Working Hypotheses: (1) Glutamatergic mechanisms reflecting plastic synaptic processes contribute to the homeostatic build-up of sleep need during wakefulness in genetically characterized persons. (2) Selective, negative allosteric modulation of mGluR5 attenuates EEG markers of sleep homeostasis similarly to the adenosine receptor antagonist caffeine. (3) Disturbed glutamatergic mechanisms contribute to reduced vigilance and impaired mood in patients with iHS and MDD.4. Experimental Design and Methods: An integrative, multi-modal approach combining positron emission tomography (PET), magnetic resonance spectroscopy (1H-MRS), functional magnetic resonance imaging (fMRI), human genetics, selective pharmacology, EEG mapping, neurobehavioral testing and mood assessments will be employed.5. Expected Value of the Proposed Project: The proposed studies aim at elucidating a specific role for glutamatergic mechanisms in linking sleep homeostasis with plastic synaptic processes occurring during wakefulness. In collaboration with clinical researchers, the project aims to reveal pathophysio¬logical underpinnings of iHS and MDD. Ultimately, these insights may lead to novel targets to treat sleep-wake related disorders and hint towards the function(s) of sleep.