Abstract
Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods: We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results: The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion: This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time.
Highlights
The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders
Our study aims to elucidate underlying metabolic changes related to stress using untargeted comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) sampling of the healthy human urinary volatile metabolome throughout the natural diurnal cortisol cycle
headspace of biological samples using solid-phase microextraction (HS-SPME)-GC×GC-TOFMS analysis allows for the detection of a wide range of volatile organic compounds for use in predicting total free urinary cortisol in urine across the diurnal rhythm
Summary
The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. The predictable daily pattern of cortisol synthesis, known as the diurnal cortisol rhythm, is regulated by a complex network of interacting transcription factors and glucocorticoid-induced signaling cascades (i.e., negative feedback loop) within the HPA axis [2,3]. Studies have long associated the dysregulation of the HPA axis with mental health and mood disorders, with specific emphasis on depression; underlying mechanisms still require further elucidation [4,5,6,7]. Alterations to HPA signaling mechanisms and GR sensitivity over time can Metabolites 2020, 10, 194; doi:10.3390/metabo10050194 www.mdpi.com/journal/metabolites
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