Mariska Bot1, Yuri Milaneschi2, Tahani Al-Shehri3, Najaf Amin4, Sanzhima Garmaeva5, Gerrit L J Onderwater6, Rene Pool7, Carisha S Thesing2, Lisanne S Vijfhuizen8, Nicole Vogelzangs9, Ilja C W Arts10, Ayse Demirkan11, Cornelia van Duijn4, Marleen van Greevenbroek12, Carla J H van der Kallen12, Sebastian Köhler13, Lannie Ligthart7, Arn M J M van den Maagdenberg14, Dennis O Mook-Kanamori3, Renée de Mutsert3, Henning Tiemeier4, Miranda T Schram12, Coen D A Stehouwer12, Gisela M Terwindt6, Ko Willems van Dijk15, Jingyuan Fu16, Alexandra Zhernakova5, Marian Beekman17, P Eline Slagboom17, Dorret I Boomsma7, Brenda W J H Penninx2. 1. Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. Electronic address: m.bot@ggzingeest.nl. 2. Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. 3. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 4. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. 5. Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands. 6. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. 7. Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit, Amsterdam, The Netherlands. 8. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. 9. Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands. 10. Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands. 11. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Human Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. 12. Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. 13. Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. 14. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. 15. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands. 16. Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands; Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands. 17. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.
BACKGROUND:Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.
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