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).

Study Objectives Total sleep deprivation is known to have significant detrimental effects on cognitive and socio-emotional functioning. Nonetheless, the mechanisms by which total sleep loss disturbs decision-making in social contexts are poorly understood. Here, we investigated the impact of total sleep deprivation on approach/avoidance decisions when faced with threatening individuals, as well as the potential moderating role of sleep-related mood changes. Methods Participants (n = 34) made spontaneous approach/avoidance decisions in the presence of task-irrelevant angry or fearful individuals, while rested or totally sleep deprived (27 hours of continuous wakefulness). Sleep-related changes in mood and sustained attention were assessed using the Positive and Negative Affective Scale and the psychomotor vigilance task, respectively. Results Rested participants avoided both fearful and angry individuals, with stronger avoidance for angry individuals, in line with previous results. On the contrary, totally sleep deprived participants favored neither approach nor avoidance of fearful individuals, while they still comparably avoided angry individuals. Drift-diffusion models showed that this effect was accounted for by the fact that total sleep deprivation reduced value-based evidence accumulation toward avoidance during decision making. Finally, the reduction of positive mood after total sleep deprivation positively correlated with the reduction of fearful display avoidance. Importantly, this correlation was not mediated by a sleep-related reduction in sustained attention. Conclusions All together, these findings support the underestimated role of positive mood-state alterations caused by total sleep loss on approach/avoidance decisions when facing ambiguous socio-emotional displays, such as fear.