title: The circadian regulation of sleep: impact of a functional ADA-polymorphism and its association to working memory improvements.
abstract: Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle.
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Carolin F
authors.initials: CF
authors.lastname: Reichert
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Micheline
authors.initials: M
authors.lastname: Maire
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gabel
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hofstetter
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Antoine U
authors.initials: AU
authors.lastname: Viola
authors.affiliation: Division of Clinical Psychology, Psychotherapy and Health Psychology, Institute for Psychology, University of Salzburg, 5020, Salzburg, Austria.
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Kolodyazhniy
authors.affiliation: Respiratory Medicine, Department of Internal Medicine, University Hospital Basel, 4031, Basel, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Strobel
authors.affiliation: Department of Psychiatry, Public Health Office, 60313, Frankfurt am Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Goetz
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, 8057, Zürich, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bachmann
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, 8057, Zürich, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Landolt
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Cajochen
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, 4012, Basel, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Schmidt
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D011110:Polymorphism, Genetic; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology; D055815:Young Adult
chemical_list: C548482:ADA protein, human; D000243:Adenosine Deaminase