Abstract
Objective: We first sought to examine the relationship between plasma levels of methylxanthines (caffeine and its metabolites) and sleep disorders, and secondarily between polygenic risk scores (PRS) of caffeine consumption or sleep duration with methylxanthine plasma levels and/or sleep disorders in a psychiatric cohort.Methods: Plasma levels of methylxanthines were quantified by ultra-high performance liquid chromatography/tandem mass spectrometry. In inpatients, sleep disorder diagnosis was defined using ICD-10 “F51.0,” sedative drug intake before bedtime, or hospital discharge letters, while a subgroup of sedative drugs was used for outpatients. The PRS of coffee consumption and sleep duration were constructed using publicly available GWAS results from the UKBiobank.Results: 1,747 observations (1,060 patients) were included (50.3% of observations with sleep disorders). Multivariate analyses adjusted for age, sex, body mass index, setting of care and psychiatric diagnoses showed that patients in the highest decile of plasma levels of methylxanthines had more than double the risk for sleep disorders compared to the lowest decile (OR = 2.13, p = 0.004). PRS of caffeine consumption was associated with plasma levels of caffeine, paraxanthine, theophylline and with their sum (β = 0.1; 0.11; 0.09; and 0.1, pcorrected = 0.01; 0.02; 0.02; and 0.01, respectively) but not with sleep disorders. A trend was found between the PRS of sleep duration and paraxanthine levels (β = 0.13, pcorrected = 0.09).Discussion: Very high caffeine consumption is associated with sleep disorders in psychiatric in- and outpatients. Future prospective studies should aim to determine the benefit of reducing caffeine consumption in high caffeine-consuming patients suffering from sleep disorders.
Highlights
Sleep disorders are a worldwide public health problem and their prevalence rates can vary considerably [1]
A 50% prevalence rate of sleep disorders was measured in the present psychiatric cohort, which is in agreement with previous epidemiological studies in psychiatry reporting prevalence rates between 30 and 80% depending on the definition used [1, 41]
The main result of the present study is that caffeine consumption, estimated by caffeine and its metabolite plasma levels, was associated with the occurrence of sleep disorders in psychiatry, with patients in the highest decile of caffeine and its metabolite plasma levels being more than two times more prone to sleep disorders
Summary
Sleep disorders are a worldwide public health problem and their prevalence rates can vary considerably [1]. There are several types of sleep disorders [2] and, efforts have been made to better homogenize their definition, to date, sleep disorders remain poorly described [3]. Many genes have been associated with sleep regulation, some of them being associated with specific types of sleep disorders [4]. Only a few genes are known to be responsible for severe sleep disorders [5]. Eighty to 90% of major depressive patients suffer from insomnia [6,7,8], which appears before (>40%) or at the same time (>22%) as mood disorder symptoms [9]. Sleep and psychiatric disorders share a complex two-way relationship
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