AUTHOR=Soundararajan Soundarya , Kazmi Narjis , Brooks Alyssa T. , Krumlauf Michael , Schwandt Melanie L. , George David T. , Hodgkinson Colin A. , Wallen Gwenyth R. , Ramchandani Vijay A. 

TITLE=FAAH and CNR1 Polymorphisms in the Endocannabinoid System and Alcohol-Related Sleep Quality

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.712178

DOI=10.3389/fpsyt.2021.712178

ISSN=1664-0640

ABSTRACT=<p>Sleep disturbances are common among individuals with alcohol use disorder (AUD) and may not resolve completely with short-term abstinence from alcohol, potentially contributing to relapse to drinking. The endocannabinoid system (ECS) is associated with both sleep and alcohol consumption, and genetic variation in the ECS may underlie sleep-related phenotypes among individuals with AUD. In this study, we explored the influence of genetic variants in the ECS (Cannabinoid receptor 1/<italic>CNR1</italic>: rs806368, rs1049353, rs6454674, rs2180619, and Fatty Acid Amide Hydrolase/<italic>FAAH</italic> rs324420) on sleep quality in individuals with AUD (<italic>N</italic> = 497) and controls without AUD (<italic>N</italic> = 389). We assessed subjective sleep quality (from the Pittsburgh Sleep Quality Index/PSQI) for both groups at baseline and objective sleep efficiency and duration (using actigraphy) in a subset of individuals with AUD at baseline and after 4 weeks of inpatient treatment. We observed a dose-dependent relationship between alcohol consumption and sleep quality in both AUD and control groups. Sleep disturbance, a subscale measure in PSQI, differed significantly among <italic>CNR1</italic> rs6454674 genotypes in both AUD (<italic>p</italic> = 0.015) and controls (<italic>p</italic> = 0.016). Only among controls, neuroticism personality scores mediated the relationship between genotype and sleep disturbance. Objective sleep measures (sleep efficiency, wake bouts and wake after sleep onset), differed significantly by <italic>CNR1</italic> rs806368 genotype, both at baseline (<italic>p</italic> = 0.023, 0.029, 0.015, respectively) and at follow-up (<italic>p</italic> = 0.004, <italic>p</italic> = 0.006, <italic>p</italic> = 0.007, respectively), and by <italic>FAAH</italic> genotype for actigraphy recorded sleep duration at follow-up (<italic>p</italic> = 0.018). These relationships suggest a significant role of the ECS in alcohol-related sleep phenotypes.</p>