vasoactive-intestinal-peptide and Sleep-Initiation-and-Maintenance-Disorders

Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.

Topics: Adult; Body Mass Index; Circadian Rhythm; Depression; F-Box Proteins; Female; Genetic Variation; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Orexin Receptors; Period Circadian Proteins; Polymorphism, Single Nucleotide; ras Proteins; RGS Proteins; Sleep Apnea Syndromes; Sleep Initiation and Maintenance Disorders; Vasoactive Intestinal Peptide

Twenty-four cats were implanted with electrodes for chronic sleep recordings. One week after the surgery, cats were treated with two intraperitoneal injections of parachlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, to induce insomnia. Twenty-four hours after the second injection of PCPA, cats were at the peak of insomnia (strong reduction of both slow wave sleep 2 and rapid-eye movement [REM] sleep). During this period cats were divided into four groups (n = 6) and were injected with either atropine (0.5 mg/kg, IM [3.5 mmol/kg]), vasoactive intestinal peptide (VIP) (200 ng, ICV [60 pmol]) or atropine plus VIP (same doses and routes of administration). The control group received saline intramuscularly (IM) intracerebroventricularly and (ICV). Results showed that VIP and atropine injected alone and in combination increased mean total time of REM sleep in PCPA-treated animals. These findings are discussed in terms of a serotonin-acetylcholine interaction.

Topics: Animals; Atropine; Cats; Drug Interactions; Electroencephalography; Female; Fenclonine; Male; Reaction Time; Sleep Initiation and Maintenance Disorders; Sleep, REM; Vasoactive Intestinal Peptide