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Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans

Bachmann, Valérie ; Klaus, Federica ; Bodenmann, Sereina ; Schäfer, Nikolaus ; Brugger, Peter ; Huber, Susanne ; Berger, Wolfgang ; Landolt, Hans-Peter

In: Cerebral Cortex, 2012, vol. 22, no. 4, p. 962-970

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    Title
    • Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans
    Author
    • Bachmann, Valérie. Institute of Pharmacology and Toxicology University of Zurich, Zurich, Switzerland
    • Klaus, Federica. Institute of Pharmacology and Toxicology University of Zurich, Zurich, Switzerland
    • Bodenmann, Sereina. Institute of Pharmacology and Toxicology University of Zurich, Zurich, Switzerland
    • Schäfer, Nikolaus. Institute of Medical Molecular Genetics, University of Zurich, Schwerzenbach, Switzerland
    • Brugger, Peter. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    • Huber, Susanne. Clinical Psychology and Psychotherapy Lab, University of Zurich, Switzerland
    • Berger, Wolfgang. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    • Landolt, Hans-Peter. Institute of Pharmacology and Toxicology University of Zurich, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Cerebral Cortex, 2012, vol. 22, no. 4, p. 962-970. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:296710
    Summary
    Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans