title: A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans.
abstract: Slow, rhythmic oscillations (<5 Hz) in the sleep electroencephalogram may be a sign of synaptic plasticity occurring during sleep. The oscillations, referred to as slow-wave activity (SWA), reflect sleep need and sleep intensity. The amount of SWA is homeostatically regulated. It is enhanced after sleep loss and declines during sleep. Animal studies suggested that sleep need is genetically controlled, yet the physiological mechanisms remain unknown. Here we show in humans that a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and SWA during sleep. In contrast, a distinct polymorphism of the adenosine A(2A) receptor gene, which was associated with interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers, affects the electroencephalogram during sleep and wakefulness in a non-state-specific manner. Our findings indicate a direct role of adenosine in human sleep homeostasis. Moreover, our data suggest that genetic variability in the adenosinergic system contributes to the interindividual variability in brain electrical activity during sleep and wakefulness.
authors.affiliation: Institute of Pharmacology and Toxicology and Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: J V
authors.initials: JV
authors.lastname: Rétey
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.forename: E
authors.initials: E
authors.lastname: Honegger
authors.forename: R
authors.initials: R
authors.lastname: Khatami
authors.forename: U F O
authors.initials: UF
authors.lastname: Luhmann
authors.forename: H H
authors.initials: HH
authors.lastname: Jung
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: H-P
authors.initials: HP
authors.lastname: Landolt
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D004569:Electroencephalography; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D012890:Sleep / Q000235:genetics* / Q000502:physiology; D013997:Time Factors
chemical_list: D000243:Adenosine Deaminase