0036 ARC Genotype Modulates REM EEG Spectral Power Following Total Sleep Deprivation

Abstract Introduction EEG spectral power in the alpha range is indicative of a wake-like state, with alpha power typically high during wakefulness and reduced during sleep. We previously reported that a single nucleotide polymorphism (SNP) of the activity-regulated cytoskeleton associated protein (ARC) gene modulates non-REM theta and alpha spectral power. Here we sought to determine whether ARC genotype is also associated with phenotypic differences in EEG spectral power during REM sleep. Methods 43 healthy adults (27.6±4.8y; 23 females) participated in one of two in-laboratory studies. Each participant had a 10h baseline sleep opportunity (22:00–08:00), 38h TSD, and 10h recovery sleep opportunity (22:00–08:00). Sleep periods were recorded polysomnographically and visually scored according to AASM criteria. Genomic DNA was assayed for the ARC c.*742 + 58C>T non-coding SNP, rs35900184. Log-transformed EEG spectral power (C3-M3 derivation) for REM sleep over 0.2 Hz frequency bins in each of four frequency bands – delta (0.8–4.0 Hz), theta (4.2–8.0 Hz), alpha (8.2–12.0 Hz), and beta (12.2–16.0 Hz) – was analyzed by band using mixed-effects ANOVA with fixed effects for ARC genotype, night (baseline, recovery), frequency bin, and their interactions. Analyses included study and age as covariates and a random effect over subjects on the intercept. Results The genotype distribution in this sample was 28 C/C homozygotes, 10 C/T heterozygotes, and 5 T/T homozygotes. There was a significant genotype by night interaction in the alpha band (F2,1560=23.80, p< 0.001). Compared to baseline sleep, T/T homozygotes had 13.0% more alpha power during post-TSD recovery sleep, whereas C/C homozygotes had 1.2% less alpha power and C/T heterozygotes had 3.2% less alpha power. This differential TSD effect for the ARC genotypes was not seen in the other spectral bands. Conclusion Our results show that ARC genotype mediates the REM sleep EEG response to TSD, with T/T homozygotes displaying a pronounced increase in REM alpha power following sleep deprivation. The ARC SNP has been associated with schizophrenia, a psychiatric disorder with known sleep disturbances. As such, the ARC-mediated increase in REM EEG alpha power for T/T homozygotes might be a marker of a psychosis-like predisposition. Support (if any) ONR N00014-13-1-0302; NIH R21CA167691; USAMRDC W81XWH-18-1-0100; ARO W911NF2210223