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Abstract Details
Depressive symptoms in non-alcoholic fatty liver disease are identified by perturbed lipid and lipoprotein metabolism
PLoS One. 2022 Jan 6;17(1):e0261555. doi: 10.1371/journal.pone.0261555. eCollection 2022.
Daniel E Radford-Smith123, Preya J Patel45, Katharine M Irvine67, Anthony Russell89, Dan Siskind1011, Daniel C Anthony1, Elizabeth E Powell612, Fay Probert2
Author information
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.
Institute for Liver and Digestive Health, University College London, London, United Kingdom.
The Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Centre for Liver Disease Research, The University of Queensland, Brisbane, Australia.
Mater Research, The University of Queensland, Brisbane, Australia.
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia.
Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
School of Clinical Medicine, The University of Queensland, Woolloongabba, QLD, Australia.
Metro South Addiction and Mental Health Service, Woolloongabba, QLD, Australia.
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Abstract
Non-alcoholic fatty liver disease (NAFLD) and depression are common disorders and have bidirectional contributing relationships to metabolic syndrome. We aimed to determine whether a fasting serum signature of recent, self-reported depressive symptoms could be identified in a heterogeneous NAFLD cohort using nuclear magnetic resonance (NMR)-based metabolomics integrated with clinical chemistry. Serum nuclear magnetic resonance (NMR) metabolite profiles and corresponding clinical chemistry were compared between patients with depressive symptoms in the last 12-months (n = 81) and patients without recent depressive symptoms (n = 137 controls) using multivariate statistics. Orthogonal partial least squares discriminant analysis (OPLS-DA) of the biochemical and metabolomic data identified NAFLD patients with recent depression with a cross-validated accuracy of 61.5%, independent of age, sex, medication, and other comorbidities. This led to the development of a diagnostic algorithm with AUC 0.83 for future testing in larger clinical cohorts. Serum triglycerides, VLDL cholesterol, and the inflammatory biomarker GlycA were key metabolites increased in patients with recent depressive symptoms, while serum glutamine level was reduced. Here, serum NMR metabolite analysis provides a link between disturbed lipid metabolism, inflammation, and active mental health issues in NAFLD, irrespective of disease severity.