0412 UNITED BY SLEEP ARCHITECTURE, DIVIDED BY METABOLISM: METABOLOMICS OF MILD INSOMNIA

Abstract

Introduction: Insomnia remains one of the top causes of neuropsychiatric disorders. The disease is associated with a number of negative consequences including daytime fatigue, impaired emotional and cognitive regulation and decreased quality of life. Despite being common in occurrence, very little is known about pathophysiology of the disease. Strikingly, objective measurements of sleep often fail to distinguish insomniacs from healthy controls. We investigated the metabolic profiles of insomnia patients using NMR spectroscopy based metabolomics to gain insights of the disease at a molecular level. Methods: Insomnia patients (n=15) and healthy controls (matched by age and sex, n=15) were recruited for the study. The individuals were subjected to blood draw every 2 hours for 48 hours and one night of polysomnography. Blood serum samples were extracted and analyzed by high resolution NMR spectroscopy. Spectral data was analyzed and compared using multivariate statistical tools and time series analysis. Results: Insomnia patients have distinct metabotypes from matched controls in spite of comparable sleep architecture. Metabotypes of insomnia patients were significantly different from the controls across all time points and temporally in nighttime samples. Energy, sugar, and branched chain amino acid (BCAA) metabolism were found to be distinctly altered. In addition, circadian oscillations of metabolites were impacted in insomnia patients. Specifically, we observed an imbalance of anabolic and catabolic activity in insomnia. Bedtime catabolic activity was found to be increased, as suggested by temporal buildup of catabolic products of energy substrates. Conclusion: Despite similar sleep architecture, metabolic profiles of participants with insomnia are highly distinct from control individuals. Obvious differences in the energy metabolism and BCAA metabolism may have a mechanistic connection with incidental metabolic disorders in chronic insomnia.