Prof.Dr. Hans-Peter Landolt

 

Main Goals, Keywords

Major aspects of sleep-wake regulation are genetically controlled. We are interested in genotype-dependent differences in sleep, waking performance and response to sleep- and wake-promoting pharmacological agents. To elucidate molecular mechanisms of sleep-wake regulation in health and disease, we combine and integrate methods of human genetics, selective pharmacology, multi-channel EEG, neuropsycho­logical/cognitive testing and brain imaging.

Group Members

1 senior researcher, 3 Ph.D. students, 2 M.D. students, 1 M.Sc. student

Previous and Current Research

In a convergent series of studies, we demonstrated that the adenosinergic neuromodulator/receptor system plays a key role in sleep-wake regulation in humans. We identified a genetic variation in the gene encoding adenosine deaminase that modifies functional features of sleep structure and the sleep EEG. Subsequent pharmaco-genetic studies demonstrated that adenosinergic mechanisms contribute to inter-individual variation in the detrimental effects of sleep loss on neuro­behavioral and cognitive functions, as well as in sleep disruption after caffeine consumption. These findings suggest that the andenosinergic system may provide new targets for pharmacological improvement of disordered sleep and vigilance, which are highly prevalent in society. Our current studies also extend to monoaminergic and glutamatergic mechanisms of sleep-wake regulation. They showed that a functional polymorphism in the gene encoding catechol-O-methyltransferase potently modulates the efficacy of modafinil on vigor, well-being, executive functioning and attention after sleep loss. This polymorphism also predicts inter-individual variation in brain alpha oscillations in young men, but does not affect established EEG markers of sleep regulation in recovery sleep.

To investigate pathophysiological underpinnings of disturbed sleep-wake functions in patients with neurological diseases, we are part of an inter-disciplinary network of neuro­scientists and clinical researchers. In projects spanning from the molecular level to sleep-wake behavior and cognitive task performance to clinical sleep neurophysiology, we recently provided new insights into sleep-wake disturbances in patients with sporadic Creutzfeldt-Jakob disease and narcolepsy. In a collaborative effort, we examined whether high and lower cognitive abilities are associated with individual differences in sleep duration and distinct features of sleep. Sleep-wake regulation and EEG patterns are studied in cognitively well-characterized children and adults with distinct genotypes in neuromodulatory systems related to cognition and sleep, and in patients with cortical and thalamic stroke. The studies will show whether neuronal plasticity and sleep are functionally related in humans, and possibly contribute to improved patient care in the future.

Future Projects

We aim to identify further genetic contributions to sleep, sleep-wake regulation and individual responses to pharmacological agents interfering with the quality of waking and sleep.

Techniques and Equipment

Four‑bedroom temporal isolation unit equipped for 32-channel long-term digital, polysomnographic recordings; portable 128-channel high-density EEG system; several portable recording systems for clinical and home recordings; analysis software for sleep, EEG spectral analysis, and brain imaging data; actimetry devices to record wrist activity/light exposure; validated questionnaires and tests to asses neurobehavioral, neurocognitive and affective performance and state; assays for genotype, pharmacokinetic and biochemical analyses.

Selected Publications

• Bodenmann, S., Rusterholz, T., Dürr, R., Stoll, C., Bachmann, V., Geissler, E., Jaggi-Schwarz, K., Landolt, H.P. The functional Val158Met polymorphism of COMT predicts individual differences in brain alpha oscillations. J Neurosci 29, 10855-10862 (2009).
• Bodenmann, S., Xu, S., Luhmann UFO, Arand, M., Berger, W., Jung, H.H., Landolt H.P. Pharmacogenetics of modafinil after sleep loss: Catechol-O-Methyltransferase genotype modulates waking functions but not recovery sleep. Clin Pharmacol Ther 85, 296-304 (2009).
• Landolt, H.P. Genotype-dependent differences in sleep, vigilance and response to stimulants. Curr Pharm Des 14, 3396-3407 (2008).

Selected Lectures, Seminars, Colloquia

• Vorlesungen für Studierende der Humanmedizin (2., 3., 4. & 6. Jahreskurs)
• Pharmakologie und Toxikologie für Studierende der Zahnmedizin (3. Jahreskurs)
• Blockkurs "Experimentelle Humanstudien in Physiologie und Pharmakologie" (BIO 406)
• Kolloquium "Recent Advances in Sleep Research"

Funding

Swiss National Science Foundation, Novartis Stiftung für medizinisch-biologische Forschung, National Center for Competence in Research (NCCR) „Neural Plasticity and Repair", Helene Bieber-Fonds, Anna Feddersen-Wagner-Fonds, Schüller Stiftung, OPO Stiftung

URL

http://www.pharma.uzh.ch/research/chronobiology/areas/psychopharmacology.html