Work

ARC genotype modulates slow wave sleep and spectral power in the sleep EEG after total sleep deprivation

Year: 2025

Type: article

Abstract: Study Objectives There are large individual differences in the homeostatic response to sleep deprivation, as reflected in slow wave sleep (SWS) and electroencephalogram (EEG) spectral power, which have largely been left unexplained. Recent evidence suggests the possible involvement of the activity-regulated cytoskeleton-associated protein (ARC) gene. Here we assessed the effects of the “c.*742 + 58C > T non-coding single nucleotide polymorphism” of the human ARC gene (rs35900184) on sleep-physiological and waking-neurobehavioral responses to total sleep deprivation (TSD). Methods N = 50 healthy, young adults participated in a 4-day/3-night in-laboratory study with a 38-h TSD period, flanked by 10-h baseline and recovery sleep opportunities. Sleep was recorded polysomnographically and the EEG of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep was subjected to spectral analysis. Waking neurobehavioral functioning was measured with the psychomotor vigilance test (PVT) and the Karolinska Sleepiness Scale (KSS). Results ARC C/C homozygotes, compared to T allele carriers, showed a greater SWS rebound during recovery sleep after TSD relative to baseline. ARC T/T homozygotes showed increased EEG spectral power in the NREM theta and alpha bands and in the REM delta, theta, alpha, and beta bands, but there was no significant genotype difference in the NREM delta power response to TSD. There were also no significant genotype differences in the impact of TSD on PVT performance and KSS sleepiness. Conclusions Individual differences in the sleep physiological rebound after TSD were influenced by ARC genotype. However, our findings were only partially consistent with ARC mediating the sleep homeostatic response to sleep deprivation. This article is part of the Genetic and Other Molecular Underpinnings of Sleep, Sleep Disorders, and Circadian Rhythms Including Translational Approaches Collection. Statement of Significance This study showed that individual differences in the human sleep physiological response to total sleep deprivation are partially predicted by cytoskeleton-associated protein (ARC) genotype, and that ARC may play a role in the homeostatic regulation of sleep. However, ARC also affected the non-rapid eye movement and rapid eye movement sleep electroencephalogram in ways that may not pertain to homeostatic sleep regulation through mechanisms that have yet to be identified.

Source: SLEEP Advances

DOI: 10.1093/sleepadvances/zpaf041