Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882).

Mégane Erblang,Catherine Drogou,Mathias Guillard,Mounir Chennaoui,Danielle Gomez-Merino,Pascal Van Beers,Damien Léger,Arnaud Rabat,Cyprien Bourrilhon,Aurélie Trignol,Michaël Quiquempoix,Fabien Sauvet,Claire Thomas,Marie-Claire Erkel

doi:10.3390/genes12040555

Abstract

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

Highlights

Several professions are exposed to prolonged wakefulness resulting in an increased risk of accident [1]
Our study aimed to evaluate the influence of four single nucleotide polymorphisms (SNPs) and caffeine effects on Psychomotor vigilance task (PVT) psychomotor vigilance and subjective sleepiness during 38 h of prolonged wakefulness in healthy subjects
Our study demonstrated for the first time, in a relevant number of subjects, that genes can influence the levels of psychomotor vigilance impairments associated with total sleep deprivation and their modulation by caffeine administration

Summary

Introduction

Several professions are exposed to prolonged wakefulness resulting in an increased risk of accident [1]. Many studies have shown that total sleep deprivation (TSD) increased daytime sleepiness and decreased sustained attention [2,3]. It is well established that during sleep loss, the most consistent parameter affected is sustained attention, which is in most research, assessed through the Psychomotor vigilance task (PVT) [4,5]. Caffeine is the major worldwide most available stimulant, used by professionals to counteract sleep loss-related neurobehavioral impairment and was shown to significantly increase alertness and decrease subjective sleepiness [6]. From a physiological point of view, caffeine globally promotes wakefulness by unselectively antagonizing adenosine receptors, A2A, in the brain regions, and helps to restore cognitive function after TSD, often by preventing a decrease in sustained attention [7]. The arousal effect of caffeine has been found mediated by A2A receptors [7]

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Results

Discussion

Conclusion